The Cure Our Children Foundation New and Emerging Treatments for Ewing's Sarcoma Weblog (http://www.cureourchildren.org)

GUMC Discovery Highlights New Direction For Drug Discovery

Barry Sugarman — Mon, 06 Jul 2009 14:04:34 -0700

http://explore.georgetown.edu/news/?ID=42483&PageTemplateID=295

FOR IMMEDIATE RELEASE: July 5, 2009

CONTACT:	Karen Mallet 215-514-9751 mallet.karen@gmail.com

GUMC Discovery Highlights New Direction For Drug Discovery Researchers did what others thought was not possible by finding a small molecule to stop “slippery” protein from binding to another, causing Ewing’s Sarcoma
Washington, DC – In a discovery that rebuffs conventional scientific thinking, researchers at the Lombardi Comprehensive Cancer Center at Georgetown University Medical Center (GUMC) have discovered a novel way to block the activity of the fusion protein responsible for Ewing’s sarcoma, a rare cancer found in children and young adults. In the paper published online July 5 in Nature Medicine, they report discovering and successfully testing a small molecule that keeps the fusion protein from sticking to another protein that is critical for tumor formation. The researchers say this interaction is unique – and is especially surprising since the Ewing’s sarcoma fusion protein is extremely flexible, which allows it to change shape constantly. “Most targeted small molecule cancer drugs inhibit the intrinsic activity of a single protein, but our agent stops two proteins from interacting. This has never been shown before with a cancer-causing fusion protein and represents a potentially novel medical therapy in the future,” says the study’s lead investigator, Jeffrey Toretsky, MD, a pediatric oncology physician and researcher at GUMC’s Lombardi Comprehensive Cancer Center. The study could provide a model upon which to design treatment for other disorders caused by the interaction between two proteins, and may be especially useful in cancers caused by translocations of genes, such as sarcomas and leukemias, the researchers say. Agents in use now that work against fusion proteins inhibit a single protein to stop intrinsic enzymatic activity; one example is Gleevec, used for chronic myelogenous leukemia (CML). The Ewing’s sarcoma fusion protein, known as EWS-FLI1, lacks enzymatic activity, “and this difference is why our work is significant,” Toretsky says. In the United States, about 500 patients annually are diagnosed with the cancer, and they are treated with a combination of five different chemotherapy drugs. Between 60-70 percent of patients survive over time, but with side effects from the treatment. Few additional treatment options are available for patients whose cancer progresses, Toretsky says. Ewing’s sarcoma is caused by the exchange of DNA between two chromosomes, a process known as a translocation. The new EWS-FLI1 gene is created when the EWS gene on chromosome 22 fuses to the FLI1 gene on chromosome 11, and its product is the fusion protein responsible for cancer formation. It is a so-called disordered protein, which means it does not have a rigid structure. A number of cancer-causing proteins are disordered. In their 15-year search for a new treatment for Ewing’s sarcoma, Toretsky and his colleagues were the first to make a recombinant EWS-FLI1 fusion protein. They used it to discover that the fusion protein stuck to another protein, RNA helicase A (RHA), a molecule that forms protein complexes in order to control gene transcription. “We believe that when RHA binds to EWS-FLI1, the combination becomes more powerful at turning genes on and off,” says the study’s first author, Hayriye Verda Erkizan, PhD, a postdoctoral researcher in Toretsky’s lab. Then, from a library of 3,000 small molecules loaned to Georgetown from the National Cancer Institute, the researchers searched for a small molecule that would bind on to EWS-FLI1. They found one, and further discovered the same molecule, NSC635437, could stop EWS-FLI1’s fusion protein from sticking to RHA. This was a wonderful discovery, Erkizan says, because the notion long accepted among scientists is that it is not possible to block protein-protein interactions given that the surface of many of these proteins are slippery - much too flexible for a drug to bind to. They tested the agent in laboratory cell culture, and with the help of GUMC’s Drug Discovery Program, the researchers designed a stronger derivative compound they called YK-4-279. In this study, they tested YK-4-279 in two different animal models of Ewing’s sarcoma and found that the agent significantly inhibited the growth of tumors. There was an 80% reduction in the growth of treated tumors compared to untreated tumors. Toretsky says that while the agent needs to be “optimized,” these results serve as a proof of principle that inhibiting protein-protein interaction can work as a novel therapeutic that will target only cancer cells. “We may be able to use this strategy to attack proteins we thought to be impervious to manipulation,” he says. The study was funded by grants from the National Institutes of Health, Children’s Cancer Foundation of Baltimore, MD, Go4theGoal Foundation, Dani’s Foundation of Denver, the Liddy Shriver Sarcoma Initiative, the Amschwand Sarcoma Cancer Foundation, the Burroughs-Wellcome Clinical Scientist Award in Translational Research, and the GUMC Drug Discovery Program. Toretsky and co-authors Milton L. Brown, Aykut Üren and Yali Kong are inventors on a patent application that has been filed by Georgetown University related to the technology described in this paper. The other authors report no related financial interests. About Georgetown University Medical Center Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through Georgetown’s affiliation with MedStar Health). GUMC’s mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing and Health Studies, both nationally ranked, the world-renowned Lombardi Comprehensive Cancer Center and the Biomedical Graduate Research Organization (BGRO), home to 60 percent of the university’s sponsored research funding. ###

PharmaMar announced Yondelis has gained approval for price and reimbursement in Italy

Barry Sugarman — Mon, 26 Jan 2009 22:52:36 -0800

http://www.pharmamar.com/ElementoPrensa.aspx?prensa=91

PharmaMar announced Yondelis® has gained approval for price and reimbursement in Italy

Madrid, 26th January 2009: PharmaMar announced today that Yondelis® has gained approval for price and reimbursement in Italy. With this approval, PharmaMar has successfully finalised negotiations for the price and reimbursement of Yondelis® with the Italian authorities. Yondelis® will have same price it has in the rest of European countries.

Once price and reimbursement approval for Yondelis® has been gained, the next steps towards the commercialization of the drug in Italy will be taken soon. This means Yondelis ® may be commercially available to patients in Italy in the nest weeks.

YONDELIS® is currently being marketed in the European Union for the treatment of Soft tissue Sarcoma in adults after the failure of standard therapy. PharmaMar has started a phase III multicenter study of Yondelis® as first-line therapy in patients with tumor traslocation, Ewing's sarcoma, or not rhabdomyosarcomatose soft tissue sarcomas and other types of STS. Yondelis® is being studied in solid tumors with high incidence and prevalence in the population, such as prostate, breast and lung cancer.

Yondelis® has been designated orphan drug for the treatment of soft tissue sarcomas and ovarian cancer in the European Union, United States and Switzerland, and for soft tissue sarcomas in Korea.

According to the agreement between PharmaMar a subsidiary of Zeltia, S.A- and Ortho Biotech Products, L.P. a subsidiary of Johnson & Johnson- , under which Yondelis® is developed, PharmaMar will market Yondelis® in Europe (including Eastern Europe) and Japan, and Ortho Biotech Products, L.P. will market Yondelis® in the rest of the world. Both companies filed a registration dossier to the EMEA and the FDA for Yondelis for the treatment of refractory ovarian cancer at the end of 2008. At the end of 2008 both companies submitted a Registration Dossier of Yondelis® in relapsed ovarian cancer (ROC) to the EMEA and the FDA. A decision on the approval for this indication is expected to take place during 2009.

Soft tissue sarcomas
STS are a diverse group of more than 50 types of tumours that appear in fatty tissue, muscle, nerve tissue, tendons and blood and lymph vessels. Nearly half of them affect the extremities.
According to data from GEIS (Spanish research group in sarcomas) soft tissue sarcomas (STS) have an incidence of around 3/100,000 new cases per year, which represents 2% of the overall mortality from cancer. The highest incidence is situated in patients around 50 years of age.
The five-year survival rate of patients with STS is around 90% when detected early (stage I), that is, when the tumour is small and with no metastasis. However, the five-year survival rate in patients with metastatic disease is 10-20% . The estimated life expectancy in metastatic patients is 8-12 months after receiving the first line of cytotoxic therapy.

PharmaMar
PharmaMar is the world-leading biopharmaceutical company of the Zeltia Group, committed to advancing the treatment of cancer through the discovery and development of new marine-derived medicines. Yondelis® is the first Spanish antitumoral compound, currently marketed in the European
Union for the treatment of soft tissue sarcomas in adults after the failure of standard therapy. Last December 4th, 2008 PharmaMar submitted a Registration Dossier of Yondelis® in relapsed ovarian cancer (ROC) to the EMEA. A decision on the approval for this indication is expected to take place by
mid-2009. PharmaMar has four novel compounds in clinical development: Yondelis® is also in Phase II studies in prostate, breast and pediatric cancers. Aplidin ®, Zalypsis ®, and Irvalec ® are new marine-derived agents in clinical development. PharmaMar also has an extensive portfolio of products in preclinical research and a sound R&D program.

Important note
PharmaMar, based in Madrid, Spain, is a company of the Zeltia Group (Spanish Stock Exchange, ZEL) that has been listed on the Spanish Stock Exchange since 1963. This document is a press release, not a brochure. This document does not constitute nor is it part of any offer or invitation to sell or issue any application of purchase, offer, or shares subscription of the Group. Likewise, this document nor its
distribution is part or can be of base for any contract or investment decision and does not constitute any kind of recommendation in relation with the shares of the Company.

For further information:

Media Relations (Ph: +34 91 846 60 00)
Fernando Mugarza
Carlos Martínez de la Serna
Carolina Lanzas Otazu

Capital Markets ( Ph: +34 91 444 45 00)
Alfonso Hurtado de Mendoza
Florencia Radizza

This press release is also available in the News Area of www.pharmamar.com

PharmaMar presents new data of Zalypsis® and Irvalec® in pediatric, solid tumours and lymphoma at the 20th AACR-NCI-EORTC Symposium

Barry Sugarman — Sun, 02 Nov 2008 19:23:27 -0800

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NEWS RELEASE

http://www.pharmamar.com/en/press/news_release.cfm?newsReleaseID=194&year=2008

PharmaMar presents new data of Zalypsis® and Irvalec® in pediatric, solid tumours and lymphoma at the 20th AACR-NCI-EORTC Symposium

23 October 2008

- Irvalec® and Zalypsis® are two compounds of marine origin, with a novel mechanism of action, in phase I clinical development for the treatment of various tumors
- A clinical study of 37 patients with solid tumors or lymphoma shows Zalypsis has a good safety profile and is highly active. These findings enable the continuation of Zalypsis clinical development
- Irvalec® shows significant antiproliferative activity in trials against different tumor cell lines, at doses equivalent to the clinical administration and higher to those obtained with five other antitumoral compounds of ErbB pathway
- Two new preclinical studies made in collaboration with the European Consortium for Innovative Therapies for Children with Cancer (ITCC) show significant activity of the two compounds in pediatric tumors
- PharmaMar, a company of the Zeltia Group, is presenting data on four trials during the 20th EORTC-NCI-AACR symposium, held in Geneva from 21- 24 October

Geneva, 23 October, 2008: PharmaMar, a biotechnology company of Zeltia Group, has presented new data on two antitumoral compounds of marine origin, Zalypsis® and Irvalec®, in Phase I trials in clinical development and in vitro studies and with animal models.

Zalypsis® is a novel chemical entity related to the marine natural compounds Jorumycin and the family of Renieramycins, obtained from molluscs and sponges, respectively. Irvalec®, a new synthetic depsipeptide derived from PharmaMar Development Program of marine origin compounds, is a new drug with antiproliferative activity against a wide range of tumors, including breast, colon, pancreas, lung and prostate.

PharmaMar has presented the results of 4 studies at the 20th annual symposium of the European Organization for Research and Treatment of Cancer (EORTC), the U.S. National Cancer Institute (NCI) and the American Association for Cancer Research (AACR), taking place in Geneva (Switzerland) from 21 to October 24.

In the first study, the safety of Zalypsis ® in 37 patients with solid tumors or lymphoma was evaluated. The trial shows a good safety profile of the drug, which enables the

continuation of its clinical development. The study was made in collaboration with the Institut Gustave Roussy (Villejuif, France) and the Northern Centre for Cancer Treatment (Newcastle, United Kingdom).

The second study presented at the Geneva meeting evaluated the activity of Irvalec® in of colon cancer, breast, ovarian, lung, prostate, head and neck and pancreas cell lines. Cytotoxicity data obtained with Irvalec® were compared with five other compounds that inhibit the Erb-B/HER Pathway.

According to the results, Irvalec® shows a significant antiproliferative activity at doses that may be achieved in the clinic, being a more potent inhibitor of cell proliferation than other ErB inhibitors used in the trials, and showing a differential activity profile. The study was made in collaboration with the Beaujon University Hospital (Clichy, France).

In two other new studies presented at the meeting in Geneva, PharmaMar evaluated the therapeutic potential of Irvalec® and Zalypsis® in pediatric tumors.

The preclinical evaluation of the first compound for the treatment of pediatric cancer was made against six types of pediatric tumors cell lines that represent 50% of treatment failures in this population: neuroblastoma, Ewing's sarcoma, rhabdomyosarcoma, acute lymphoblastic leukemia, medulloblastoma and osteosarcoma. Osteosarcoma and rhabdomyosarcoma cell lines were the most sensitive to the drug.

The same methodology was followed for the evaluation of Zalypsis®. The most significant results in in vitro tests were obtained in neuroblastoma and rhabdomyosarcoma cell lines. The evaluation of the compound in animal models also showed significant results, especially in the activity in rhabdomyosarcoma.

The trials were conducted by the R&D Department of PharmaMar in partnership with the Emma Children's Hospital (Amsterdam, Netherlands), the University Children's Hospital (Munster, Germany) and the Institut Gustave Roussy (Villejuif, France), and members of the Innovative Therapies for Children with Cancer (ITCC) which brings together 35 centres specializing in pediatric oncology of six European countries.

The aim of the studies carried out in collaboration with ITCC is to facilitate the identification of new compounds with significant potential in the treatment of pediatric tumors.

Within PharmaMar Cancer Research Program and as part of the companys commitment with cancer patients, this biotech company of the Zeltia Group is also evaluating the therapeutic potential of its marine origin compounds in pediatric tumors.

About Zalypsis® (PM00104)
Zalypsis® (PM00104/50) is a new marine derived compound in Phase II clinical trials for the treatment of solid tumours. Zalypsis® is a novel chemical entity related to the marine natural compounds Jorumycin and the family of Renieramycins, obtained from molluscs and sponges, respectively. Zalypsis binds to DNA and is cytotoxic; however, it does not activate the DNA damage checkpoint response. Thus, Zalypsis has cytotoxic effects dependent on DNA binding that are not associated with DNA damage. In pre-clinical trials, Zalypsis demonstrated strong in vitro and in vivo antitumoural activity in a wide variety of solid and haematological tumour cell lines and human transplantable breast, gastric, prostate and renal xenografted tumours. Zalypsis also demonstrated a manageable and reversible preclinical toxicology profile.

About Irvalec® (PM02734)
Irvalec® is a new depsipeptide from PharmaMars internal research program for derivatives of the marine natural compounds. PM02734 is manufactured synthetically by PharmaMar. Preliminary in vitro in-house studies identified PM02734 as a new antiproliferative drug demonstrating activity against a broad spectrum of tumor types: breast, colon, pancreas, lung and prostate, among others. PM02734 has been selected for clinical development based on its in vivo activity in xenografted human tumors, as well as an acceptable non-clinical toxicology profile. PM02734 is in Phase I clinical trials in patients with advanced malignant solid tumors.

PharmaMar
PharmaMar is the world-leading biopharmaceutical company of the Zeltia Group, and is committed to advancing the treatment of cancer through the discovery and development of new marine-derived medicines. PharmaMar has four novel compounds in clinical development. Yondelis® has received Authorization for Commercialization from the European Commission for treating advanced soft tissue sarcoma. Yondelis® is currently being marketed in the European Union for the treatment of soft tissue sarcomas in adults after failure of standard therapy. Aplidin®, Zalypsis®, and Irvalec® are other marine-derived new agents in clinical development by PharmaMar, which also has a rich pipeline of preclinical candidates, and a strong R&D program.

For further information:

Media Relations (Ph: +34 91 846 60 00)
Fernando Mugarza
Carlos Martínez de la Serna
Carolina Lanzas Otazu

Capital Markets (Ph: +34 91 444 45 00)
Alfonso Hurtado de Mendoza
Florencia Radizza

This press release is also available in the News area at www.pharmamar.com

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Neotropix® Announces Presentation of Relevant Preclinical Results of NTX-010 in Pediatric Oncology Models

Barry Sugarman — Sun, 02 Nov 2008 19:14:55 -0800

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Neotropix® Announces Presentation of Relevant Preclinical Results of NTX-010 in Pediatric Oncology Models

Malvern, PA, October 22, 2008 Neotropix®, Inc., a clinical-stage development company focused on neuroendocrine cancer treatments, announced today exciting data from an extensive pediatric preclinical study performed by the National Cancer Institute (NCI) funded Pediatric Preclinical Testing Program on the use of NTX-010 (Seneca Valley Virus-001), a tumor-selective naturally-occurring oncolytic virus. The results support the initiation of clinical development of Neotropixs lead candidate, NTX-010 for the treatment of pediatric cancers. NTX-010 has been developed as a cancer therapeutic to treat some of the most aggressive cancers known which occur in adults including small cell lung cancer, large cell non-small cell lung cancer, as well as other adult cancers such as carcinoid and various neuroendocrine cancers.

The detailed study results are being presented at the 20th Annual Molecular Targets and Cancer Therapeutics International Meeting in Geneva, Switzerland from October 21-24, 2008. The meeting is hosted jointly by the European Organization for Research and Treatment of Cancer (EORTC), the National Cancer Institute (NCI), and the American Association for Cancer Research (AACR).

The Pediatric Preclinical Testing Program (PPTP) presentation described encouraging results from an extensive evaluation of NTX-010 in over 30 different tumor models representing the most common types of childhood solid tumors. Extensive analysis has previously determined that these carefully selected models, many derived directly from patients tumors, are predictive of clinical activity and an important tool for screening promising new drug candidates for their relevance for specific childhood cancers. The PPTP results indicated that NTX-010 was active against a wide range of pediatric solid cancers, including neuroblastoma, rhabdomyosarcoma, Wilms tumors, rhabdoid, Ewing sarcoma and glioblastoma. Complete responses were observed following a single intravenous treatment in the majority of neuroblastoma models and in all alveolar rhabdomyosarcoma tumor models, demonstrating both activity and potency.

Paul Hallenbeck, Ph.D., President and Chief Scientific Officer of Neotropix®, Inc., commented, "We are very encouraged by the results of this extensive analysis of NTX-010 in pediatric oncology models, particularly because these in vivo cancer models that the NCI has developed can prospectively identify novel agents subsequently shown to have clinical activity against specific cancers of children and adolescents.

Dr. Hallenbeck continued, We are excited that the NCI-supported Childrens Oncology Group Phase I Consortium has expressed the interest to lead an effort to test NTX-010 in pediatric patients with cancer in the near future.

Neotropix® has been working closely with many collaborators around the world, including the NCI to create a treatment paradigm shift for hard to treat cancers. The Company has developed an innovative approach to harness the power of natural products screening using viruses to kill or slow down the spread of cancer. The result has been that many viruses have been identified that may provide simple, safe and effective ways to treat patients who would otherwise fail conventional treatments using traditional small molecule and antibody approaches.

About NTX-010 and the Current Clinical Trial

NTX-010 is a natural occurring oncolytic virus, which is highly selective for certain tumor cell types expressing a biomarker that indicates the cancer has neuroendocrine properties such as synaptophysin, chromogranin A, or CD56. At least one of them is required to be positive before treatment. Unlike many previous oncolytic virus product candidates developed by others, NTX-010 is a stable, naturally occurring virus, is systemically deliverable, and has not been observed to be pathogenic to humans, and therefore, has not had to be genetically modified.

NTX-010 is systemically delivered in a single one-hour infusion on an outpatient basis at each of the treatment centers, which simplifies the treatment process for patients. The product is anticipated to have enhanced efficacy and less toxicity than currently approved therapies for permissive cancers.

The clinical trial is being conducted at multiple institutions around the country, including John Hopkins (MD), Mary Crowley (TX), Lahey Clinic (MA) and many U.S. Oncology Cooperative Group treatment sites (FL, IN, NY, OH, SC, TX, VA, and WA). In addition, other treatment centers are joining the trial in the New England area of the U.S.

The current Phase I / II clinical trial is enrolling adults (18 and over) that meet the criteria for the following cancers: carcinoid cancers (all types), large cell lung cancer-neuroendocrine, alveolar rhabdomyosarcoma, neuroblastoma, glioblastoma, Ewings family of tumors, Wilms tumors, retinoblastoma, rhabdoid, and medulloblastoma. For more about the clinical trials: www.clinicialtrials.gov

Also of note, CEO Peter Lanciano of Neotropix® will be available for one-on-one meetings with potential investors at the 7th Annual BIO Investor Forum that is taking place from October 29-31, 2008, in San Francisco, CA. At the conference, Mr. Lanciano will present a corporate overview on the Company. For more information, please visit: www.investorforum.bio.org

About Neotropix®

Neotropix® Inc., is focused on the development of anti-cancer products that have a high degree of selectivity for cancer cells resulting in an excellent safety and therapeutic efficacy profile. Neotropix® develops and commercializes systemically deliverable oncolytic viruses for the treatment of solid tumors. Capitalizing on its unique sources of naturally occurring viruses that selectively target tumors discovered using the companys proprietary technology platform Viruscreen, the Company has the knowledge and skills to translate these discoveries into commercial products. Neotropix® is committed to making a difference in the lives of cancer patients.

Neotropix® commenced operations in 2005 in Malvern, Pennsylvania. Neotropix ® is funded by venture-capital investors including Aurora Funds, Quaker BioVentures and VIMAC Ventures. For more information, please visit http://www.neotropix.com

About the Pediatric Preclinical Testing Program

The NCI-supported Pediatric Preclinical Testing Program (PPTP) is a comprehensive program to systematically evaluate new agents against childhood solid tumor and leukemia preclinical models. The PPTP is supported through an NCI research contract to St. Jude Childrens Research Hospital (SJCRH) with Dr. Peter Houghton as the Principal Investigator. Testing occurs both at SJCRH and also at subcontract sites that have expertise in specific childhood cancers, including: Childrens Hospital of Philadelphia (John Maris), Albert Einstein Medical Center (E. Anders Kolb & Richard Gorlick), Duke University (Stephen Keir), Texas Tech University Health Sciences Center (Patrick Reynolds), and Childrens Cancer Institute Australia (Richard Lock). Detailed information about the PPTP and its testing procedures is available at http://www.pptp.stjude.org.

FDA Approves Orphan Drug Status for Revolutionary Cancer Drug for Children

Barry Sugarman — Sat, 01 Nov 2008 23:59:24 -0700

For Immediate Release:

FDA Approves Orphan Drug Status for Revolutionary Cancer Drug for Children

LOS ANGELES, Calif. – October 20, 2008 – The Cure Our Children Foundation, a nonprofit charitable foundation dedicated to children, announced today that the U.S. Food and Drug Administration (FDA) has approved the Orphan Drug Designation of the foundation’s unique drug product for children with Ewing’s Sarcoma cancer. The efforts to develop this drug were made possible by the generous volunteers and researchers in private industry and at two universities.

Orphan Drug status allows for recognition of the potential viability of a drug therapy while providing a variety of benefits during the drug approval process. These benefits include waivers of certain FDA fees, the availability of government grants, and FDA attention and assistance during the review process.

This ground-breaking new drug combines two modern technologies: biotechnology and nanotechnology. This incredible technology is analogous to the concept of a Trojan Horse, and is expected to have very far reaching implications for other cancer treatments. The product consists of cell matter that is modified to have the same genetic code as the cancer cells, but that matter is not viable food for the tumor cells. The cell matter is then placed in a nanotechnology formulation which allows the matter to migrate through the body’s own vessels directly to the tumor cells. When the tumor cells uptake the matter, they cannot reproduce, and they die. Key elements of this drug technology are:

· Fewer side effects may be possible

· The drug is directed only at the tumor cell and not at healthy cells

· The product is so small that it migrates right through blood vessels and cell walls

· This technology may be applied to other diseases in the future that have a genetic component

The President of the foundation, Barry Sugarman, a 30-year veteran executive and consultant in the pharmaceutical industry, and father of a son who has survived Ewing’s Sarcoma, will continue the development of the drug product by raising money from individuals and foundations.

The Cure Our Children Foundation identifies important under-researched children's issues and devotes extensive resources to educate and guide parents, professionals, government and the public. The foundation website at www.cureourchildren.org receives thousands of website visits every month. The results of the research are provided as a public service, and are supported by donations to the foundation. The foundation has a number of other research projects underway that will continue to benefit children and families.

Contact: Barry Sugarman, B.S.ENGR., President, The Cure Our Children Foundation, mailto:barry@cureourchildren.org , Phone: 310-355-6046, Fax: 310-454-9592, http://www.cureourchildren.org

Immunotherapy in High-Risk Pediatric Sarcomas including Ewing's Sarcoma Shows Promising Response

Barry Sugarman — Sun, 10 Aug 2008 12:22:57 -0700

http://www.aacr.org/home/public--media/news.aspx?d=1112

http://clincancerres.aacrjournals.org/cgi/content/abstract/14/15/4850

Requests for reprints: Crystal L. Mackall, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 10-CRC/1W-3940, 10 Center Drive, MSC 1104, Bethesda, MD 20892-1104. Phone: 301-402-5940; Fax: 301-451-7052; E-mail Crystal L. Mackall: cm35c@nih.gov

Immunotherapy in High-Risk Pediatric Sarcomas including

Ewing's Sarcoma Shows Promising Response

August 1, 2008

PHILADELPHIA - Based on a pilot study in children with sarcoma, researchers at the National Institutes of Health (NIH) believe that immunotherapy could prove beneficial in treating high-risk forms of this cancer.

The researchers tested a novel dendritic vaccine as well as a standard flu vaccine to potentially strengthen the immune system post chemotherapy. Their findings, published in the August 1 issue of Clinical Cancer Research, a journal of the American Association for Cancer Research, show that although the dendritic vaccine they tested did not perform as well as hoped, children participating in the study responded well to the standard flu vaccine- suggesting that a strategy to bolster immune function in these patients holds promise for fighting their cancer.

Researchers also found that survival in these patients was at the higher end of what is generally seen with recurrent and/or metastatic Ewing's sarcoma (ESFT) or alveolar rhabdomyosarcoma (AR) - the two sarcomas tested in this single arm study. The 22 enrolled patients who did not receive immunotherapy had a 31 percent five-year overall survival, compared to 43 percent five-year survival in 30 patients who ultimately received the novel immunotherapy.

Although the study is small, these early findings are promising, says the study's senior investigator, Crystal Mackall, M.D., of the National Cancer Institute's (NCI) Pediatric Oncology Branch. "We need new therapies. While outcomes overall for these tumors have improved during the past 40 years, there has not been substantial improvement for patients with metastatic or recurrent disease. This study shows that immunotherapy is safe and well tolerated, and could ultimately be beneficial for this high risk population. Mackall calls the study a rational approach to improving treatment of ESFT and AR. "We now know that the immune system of patients recovering from chemotherapy is malleable, so we just need to find the best immunologic approach to exploit this window of opportunity," she said.

Both ESFT and AR develop due to chromosomal translocations, which fuse a gene from one chromosome to a different chromosome. The dendritic vaccine included peptides derived from each patient's individual cancer in a way that was designed to alert a patient's immune system to the unique genetic alteration on the cancer cells.
In this clinical trial of 52 patients, researchers attempted to use immunotherapy as "consolidation" therapy - that is, after standard therapy provided a remission. Patients underwent aphaeresis to harvest blood lymphocytes that were then frozen. From this, dendritic cells were later extracted. These are cells that present an antigen to T cells and other immune system fighters in order to elicit a response.

All patients then had chemotherapy, radiation or surgery, as appropriate, and in some cases a stem cell transplant to induce remission. The 30 patients who initiated immunotherapy received a common flu vaccine, as well as their own lymphocytes and their own dendritic cells, which had been infused with tumor antigens. Some of these patients also received interleukin-2, which stimulates activity of T cell lymphocytes.

"The good news was the surprisingly nice T cell response patients had to the flu vaccination, even relatively soon after completing chemotherapy," Mackall said. "That shows that the general idea of using immunotherapy following chemotherapy to prevent recurrence is not a flawed one. Chemotherapy depleted the immune system, but we could restore it."

The bad news, she added, is that the dendritic vaccine "was not very immunogenic. We have a long way to go to optimizing this vaccine." Current studies are underway to test a new version of the vaccine, which utilizes more mature dendritic cells and tumor lysate in lieu of the translocation peptides. Ultimately, effective immunotherapy requires that one is capable of reproducing a strong and sustained immune response to tumor antigens," she said.

Mackall also notes that the vaccine in this trial was tested in patients whose cancer had recurred or metastasized. If the favorable safety profile continues and the efficacy of the vaccine is improved with the subsequent versions, one could ultimately consider the use of immunotherapy to consolidate remission in lower risk populations.

# # #

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 28,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and 80 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication and its sixth major journal, Cancer Prevention Research, is dedicated exclusively to cancer prevention, from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Media Contact:
Jeremy Moore
267-646-0557
Jeremy.moore@aacr.org

Phase I/II Study of Targeted Gene Delivery In Vivo - Intravenous Infusions of REXIN-G - Demonstrates Dose-Dependent Anti-Tumor Activity Without Toxicity in Patients With Progressive Chemo-Resistant Bone and Soft Tissue Sarcoma (ASCO 2008)

Barry Sugarman — Tue, 03 Jun 2008 23:25:22 -0700

Phase I/II Study of Targeted Gene Delivery In Vivo - Intravenous Infusions of REXIN-G - Demonstrates Dose-Dependent Anti-Tumor Activity Without Toxicity in Patients With Progressive Chemo-Resistant Bone and Soft Tissue Sarcoma (ASCO 2008)

SAN MARINO, Calif., May 29, 2008 -- Epeius Biotechnologies

(http://www.epeiusbiotech.com) announced today the results of an on-going Phase I/II study of Rexin-G for metastatic bone and soft tissue sarcoma (J Clin Oncol 26: 14509, 2008). Rexin-G is the first and so far only targeted gene therapy vector that has been tested in the clinic (Nature Reviews/Genetics 2007). In this open label study, cohorts of 6 to 7 patients with all types of sarcoma, including osteosarcoma, Ewing's sarcoma, leiomyosarcoma, malignant fibrous histiocytoma, chondrosarcoma, fibrosarcoma, liposarcoma, angiosarcoma, spindle cell sarcoma, and malignant mixed Mullerian tumor of ovary, were treated with 1 x 10e11 cfu Rexin-G, administered i.v. over 5 minutes, 2 times a week for 4 weeks (Cumulative Dose = 8 x 10e11 cfu) followed by a 2-week rest period. Patients with Grade 1 or less toxicity were given progressive intra-patient dose-escalations consisting of additional treatment cycles of 1 to 2 x 10e11 cfu three times a week for 4 weeks (Cumulative Dose per cycle: 1.2-2.4 x 10e12 cfu).

These higher dosing regimens were associated with prolonged disease stabilization and a median overall survival of greater than 6 months, which was three times longer than that observed in the low-dose group. Further, histologic examination of resected tumors showed 50-90% necrosis. No dose-limiting toxicity was observed, even at the higher doses of Rexin-G, thus confirming that repeated infusions of Rexin-G are safe and well-tolerated. Taken together with previous clinical studies conducted in the Philippines and Japan, these studies confirm the exemplary safety and dose-dependent efficacy of Rexin-G in a broad spectrum of chemotherapy-resistant cancers.

For more information about Rexin-G, on-going clinical trials in the USA and abroad, and/or Epeius pathotropic (disease-seeking) gene delivery systems, please contact Dr. Erlinda M. Gordon at . egordon@epeiusbiotech.com

CONTACT: Erlinda M. Gordon, M.D., of Epeius Biotechnologies Corporation,+1-626-441-6695, egordon@epeiusbiotech.com

Web site: http://www.epeiusbiotech.com/

New Pfizer Data Presented on CP-751,871 across Non-Small Cell Lung Cancer and Ewing's Sarcoma

Barry Sugarman — Tue, 03 Jun 2008 23:15:00 -0700

June 02, 2008 04:02 PM Eastern Daylight Time

New Pfizer Data Presented on CP-751,871 across

Non-Small Cell Lung Cancer and Ewing’s Sarcoma

ADVIGO CP-751,871 Global Phase III Clinical Trial Program Initiated (ADVancing IGF-1R in Oncology)

2008 ASCO Annual Meeting

CHICAGO--Pfizer announced today results from several clinical trials further describing the activity of its investigational compound CP-751,871 in non-small cell lung cancer (NSCLC) and Ewing’s Sarcoma, both diseases with high unmet medical need. The three oral presentations and one poster discussion underscore that the insulin-like growth factor receptor (IGF-1R) is increasingly recognized by the medical community as a relevant target for investigation in cancer research. The results were presented at the 44^th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, IL.

Updated Response Data from the 1002 NSCLC Trial

Updated study results from a Phase II, randomized, non-comparative study showed 54 percent of patients with Stage III/IV treatment-naïve NSCLC receiving the combination CP-751,871 plus carboplatin and paclitaxel (n=97) experienced objective responses. The response rate observed for patients treated with carboplatin and paclitaxel alone was 41 percent.

Of note, 78 percent of a subset of patients with squamous cell carcinoma (n=23) and 57 percent of a subset of patients with adenocarcinoma (n=28) receiving 20 mg/kg of CP-751,871 plus carboplatin and paclitaxel experienced objective responses. Response rates were 46 percent and 25 percent, respectively, for squamous cell (n=13) and adenocarcinoma patients (n=20) receiving carboplatin and paclitaxel alone. No response advantage with CP-751,871 was seen in a subset of patients with undifferentiated tumors (Not otherwise specified, NOS).

“Patients with advanced NSCLC typically face a poor prognosis and we need to develop new strategies and new treatment combinations to improve their survival,” said lead investigator Daniel Karp, M.D., director of the M.D. Anderson Cancer Center Clinical and Translational Research Center (CTRC). “The updated study results add to our growing understanding of the potential safety and efficacy of CP-751,871. In this trial, increasing the dose to 20 mg/kg in Stage 2 of the trial resulted in an increased overall response rate in all differentiated histologies, including adenocarcinoma, non-adenocarcinoma, and particularly in squamous histologies, which we consider to be of interest for future study.”

Dr. Karp also presented progression-free survival (PFS) results from the study. At the dose level of 20 mg/kg, the observed progression-free survival was 5 months in the CP-751,871 plus carboplatin/paclitaxel arm and 4 months in the carboplatin/paclitaxel only arm. The highest observed PFS was in the group of patients with squamous histologies (5.6 months in the CP-751,871 plus carboplatin/paclitaxel arm and 4.3 months in the carboplatin/paclitaxel only arm) corresponding to the patients that demonstrated the highest response rates. PFS was defined as either the length of time before the cancer progressed or death.

In this study, CP-751,871 was generally well tolerated. The most common Grade 3 or 4 side effects reported were hyperglycemia (increased blood sugar) (20 percent) and neutropenia (30 percent).

Correlative Science Study Results Support Karp Data

This abstract summarized ancillary studies conducted to investigate the molecular make up of lung tumors and its relevance to anti-IGF-IR therapy. Members of the IGF-IR pathway appear to be expressed differentially across lung tumor histologies which may help to explain the differential activity of CP-751,871 across these histologies. Tumor differentiation also appears to play a role. Data were also presented demonstrating that EGFR inhibition sensitizes tumors to CP-751,871 treatment.

“These results help us to understand better how CP-751,871 works, provide support for our phase III trial strategy and underscore Pfizer’s commitment to bring science and innovation to the forefront of drug development,” said Antonio Gualberto, M.D., Ph.D., Global Clinical Lead for the CP-751,871 program, Pfizer Global Research and Development.

ADVIGO Phase III Registration Program (ADVancing IGF-IR in Oncology)

Based on these data, Pfizer has initiated a large global Phase III clinical trial program for CP-751,871 in NSCLC, including some studies with patients with non-adenocarcinoma (ADVIGO 1016, ADVIGO 1018). The program includes trials for patients who are newly diagnosed and for those who have already been treated with other therapies.

Pfizer has made a major commitment to CP-751,871 and has invested significant resources in the Phase III program, which will include more than 2,000 patients around the world.

For more information on the ADVIGO registration program please visit, http://PfizerCancerTrials.com.

Preliminary Data Presented on CP-751,871 in Sarcoma

Phase I data presented at ASCO showed single agent CP-751,871 was generally well-tolerated in patients with relapsed or refractory sarcoma (n=22), including Ewing’s sarcoma (n=9). A response of stable disease or better was seen in 12 out of 20 evaluable patients, including one confirmed partial response in a 12-year-old patient with Ewing’s sarcoma, the second most common malignant bone tumor in young patients and the most deadly bone tumor.

CP-751,871 was generally well tolerated in patients with relapsed or refractory sarcoma. Grade 3 or 4 treatment-related side effects reported included Grade 4 uric acid increase (n=1) and Grade 3 bilateral deep-vein thrombosis (n=1).

About CP-751,871

CP-751,871, a fully human IgG2 monoclonal antibody, is a highly specific inhibitor of the IGF-1R pathway. It is believed that through this inhibition, CP-751,871 blocks one of the key signaling pathways in cancer cells that lead to uncontrolled growth and survival of tumor cells.

Pfizer recently initiated a global Phase III clinical trial registration program for CP-751,871 in non-adenocarcinoma NSCLC. In addition, Pfizer is studying CP-751,871 in clinical trials for the treatment of many other cancers, including prostate, breast and colon cancers and Ewing’s sarcoma. To date, more than 500 patients have participated in CP-751,871 clinical trials in multiple tumor types.

About Pfizer Oncology

Pfizer Oncology is committed to the discovery, investigation and development of treatments and currently has 22 innovative compounds in clinical development across four platforms. By leveraging the strength of our resources and scientific talent, Pfizer Oncology strives to discover and develop novel treatment options to improve the outlook for oncology patients. Pfizer currently devotes more than 22 percent of its total R&D budget to the field of oncology, investing annually in worldwide research initiatives. We also partner with healthcare providers, governments and local communities around the world to provide better quality healthcare and health system support.

For more information on the above information, please visit http://www.Pfizer.com.

DISCLOSURE NOTICE: The information contained in this release is as of June 2, 2008. Pfizer assumes no obligation to update any forward-looking statements contained in this release as the result of new information or future events or developments.

This release contains forward-looking information about a product candidate, CP-751,871, including its potential benefits, that involves substantial risks and uncertainties. Such risks and uncertainties include, among other things, the uncertainties inherent in research and development; decisions by regulatory authorities regarding whether and when to approve any drug applications that may be filed for such product candidate as well as their decisions regarding labeling and other matters that could affect its availability or commercial potential; and competitive developments.

A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2007 and in its reports on Form 10-Q and Form 8-K.

Contacts

Pfizer Inc
Media:
Vanessa Aristide, 917-697-0481 or 212-733-3784
or
Investors:
Jennifer Davis, 212-733-0717

More Frequent Chemotherapy Improves Outcome for Ewing’s Sarcoma Patients, Results of Children's Oncology Group Study Protocol No. AEWS0031

Barry Sugarman — Mon, 02 Jun 2008 21:55:04 -0700

More Frequent Chemotherapy Improves Outcome for Ewing’s Sarcoma Patients
Results of Children's Oncology Group Study Protocol No. AEWS0031

ORAL PRESENTATION Lead Author: Richard B. Womer, MD
American Society for Clinical Oncology Annual Meeting
http://www.asco.org

SATURDAY, MAY 31, 3:00 PM (CDT) Children’s Hospital of Philadelphia
W375b Philadelphia, PA

Investigators from the Children’s Oncology Group (COG) have found for the first time that giving combination chemotherapy every two weeks is more effective than the same therapy given every three weeks in patients with Ewing’s sarcoma, without increasing side effects.

“These findings are convincing enough to change the standard of care for patients with localized Ewing’s sarcoma,” said lead author Richard B. Womer, MD, senior oncologist and professor of pediatrics at the Children’s Hospital of Philadelphia and the University of Pennsylvania School of Medicine. “This study shows that progress against Ewing’s sarcoma can be made by giving commonly used anti-cancer drugs in new ways.”

Ewing’s sarcoma is a cancer that most often develops in the bones but can also form in soft tissue. It is generally diagnosed in children. Until this study, the standard treatment for this cancer included chemotherapy with the drugs vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide given every three weeks, as well as surgery and/or radiation therapy. With the development of better ways to bolster the immune and blood-forming systems of the body—enabling patients to tolerate more frequent chemotherapy—researchers seeking to improve treatments for several types of cancer have hypothesized that giving chemotherapy more frequently might be more effective than conventional approaches, without causing undue side effects.

In this study, researchers at 160 COG institutions sought to determine if giving the same five drugs every two weeks was more effective than giving them every three weeks in patients with Ewing’s sarcoma who were younger than 50 and had not yet had chemotherapy or radiation therapy. Primary treatment (surgery, radiation therapy, or both) began 13 weeks after chemotherapy was initiated. Event-free survival (the percentage of patients who did not die or experience a relapse or second cancer) was compared between 284 patients who received chemotherapy every two weeks and 284 who received the same regimen every three weeks. Patients in both groups received a total of 14 cycles of chemotherapy.

After a median follow-up of three years, event-free survival was 76 percent among the patients who received chemotherapy every other week, compared with 65 percent among those who received chemotherapy every three weeks. The incidence and severity of side effects remained similar between the two groups. Fever with low white blood cell count occurred in 7 percent of those in the two-week arm and 6 percent of those in the three-week arm; the incidence of infection was 4.8 percent and 4.6 percent,
respectively.

Abstract #10504

Randomized comparison of every-two-week v. every-three-week chemotherapy in Ewing sarcoma family tumors (ESFT). R. B. Womer, D. C. West, M. D. Krailo, P. S. Dickman, B. Pawel, E. for the Children's Oncology Group AEWS0031 Committee

Background: Chemotherapy with alternating cycles of vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide, and primary tumor treatment with surgery and/or radiation therapy, is the usual approach to localized ESFT in North America. We conducted a trial asking whether chemotherapy intensification through interval compression could improve outcome.

Methods: This was a prospective randomized-controlled trial for patients less than 50 y old with extra-dural ESFT, without distant metastases or prior chemotherapy or radiation therapy; and with adequate renal, cardiac, and hepatic function. Patients were treated with vincristine (2 mg/sq.m, max. 2 mg), doxorubicin (75 mg/sq.m) and cyclophosphamide (1.2 g/sq.m) alternating with ifosfamide (9 g/sq.m) and etoposide (100 mg/sq.m/), for 14 cycles, with filgrastim (5 mg/kg/day, maximum 300 mg) between cycles. Patients assigned to Regimen A were scheduled to begin chemotherapy cycles every 21 days, and patients assigned to Regimen B were scheduled to begin cycles every 14 days, or when ANC > 750 and platelets > 75. Primary tumor treatment (surgery, radiation, or both) was scheduled to begin week 13 (after 4 cycles in Regimen A and 6 cycles in Regimen B). The primary endpoint was event-free survival using a two-sided log-rank test with size 0.05 and power 0.8 to detect a 13% Embargoed Until May 15, 2008 at 9:00pm (EDT) 12 change in EFS from 60%, with 264 patients in each arm.

Results: 587 patients were enrolled and randomized, and 568 were eligible, 284 in each regimen. For all courses, the median cycle interval for Regimen A was 21 days, mean 23.3 days; in Regimen B, the median interval was 15 days, mean 18.5 days. Event-free survival at a median of 3 years was 65% in Regimen A and 76% in Regimen B, p=0.028. The occurrence of specific toxicities and the number of hospital days were similar for the two regimens.

Conclusions: Every-2-week chemotherapy is more effective than every-three-week chemotherapy for localized ESFT, with no increase in toxicity.

Disclosures for Research Team: Nothing to disclose.

ZIOPHARM Presents Promising Early Data from Phase Ib Study of Indibulin at 6th International Symposium on Targeted Anticancer Therapies

Barry Sugarman — Mon, 12 May 2008 16:30:15 -0700

ZIOPHARM Presents Promising Early Data from Phase Ib Study of

Indibulin at 6th International Symposium on Targeted Anticancer

Therapies

Results Shows Indibulin Is Well Tolerated and Active Among Eight
Evaluable Patients

http://ir.ziopharm.com/releasedetail.cfm?ReleaseID=300540

BETHESDA, Md., Mar 20, 2008 (BUSINESS WIRE) -- ZIOPHARM Oncology, Inc. (NASDAQ:ZIOP) announced today that it presented promising early data from a Phase Ib study of indibulin, the Company's novel, orally administered, synthetic tubulin targeted agent, at the 6th International Symposium on Targeted Anticancer Therapies held in Bethesda, Maryland, March 20 to 22.

A total of 14 patients with a variety of cancers, including sarcomas and carcinomas, have been treated to date in the study. Following a total of 30 cycles of treatment, indibulin has been shown to be very well tolerated, with no drug-related Grade 2 or higher toxicities reported. Of note, no neurotoxicities, a common and serious side effect typically associated with microtubule targeting agents, have been observed.

In addition to confirming indibulin's safety profile, this study evaluates early treatment responses by PET scans. Among 8 evaluable patients, these PET scans demonstrated a substantial anti-tumor effect by indibulin. Week 7 PET scans identified 1 complete reduction in uptake, 4 with partial reduction in uptake, and 3 with increased uptake. Tumor responses measured by PET scan are generally referred to as metabolic responses, and usually correlate with treatment responses in cancer.

"Safely and effectively targeting microtubules in cancer cells has long been a goal of researchers as it leads to a variety of anti-cancer activity, including antiangiogenesis and antimetastasis," commented Sant P. Chawla, MD, Director, Sarcoma Oncology Center and a lead investigator of the study. "Yet to date, these agents have all demonstrated serious side effects. Oral indibulin, by contrast, has been very well tolerated, with none of the neurotoxicity or bone marrow suppression seen with taxanes and vinca alkaloids. Indibulin has also demonstrated promising early activity by PET scan, including a complete response in Ewing's Sarcoma and a partial response in a neuroendocrine cancer. Taken together, these results are highly compelling, making ongoing study a priority."

For more details on these trials please see www.clinicaltrials.gov.

About Indibulin

Indibulin is a novel synthetic anti-mitotic agent that binds to tubulin, destabilizes microtubule polymerization, arrests tumor cell growth at the G2/M phase and inhibits cell mobility and metastasis. Microtubules are well-established targets for anti-cancer drug development and tubulin-binding drugs such as taxanes and vinca alkaloids are currently widely used to treat cancer. Indibulin is orally available, lacks neurotoxicity and has efficacy in taxane refractory preclinical models.

About ZIOPHARM Oncology, Inc.

ZIOPHARM Oncology, Inc. is a biopharmaceutical company engaged in the development and commercialization of a diverse, risk-sensitive portfolio of in-licensed cancer drugs to address unmet medical needs. The Company applies new insights from molecular and cancer biology to understand the efficacy and safety limitations of approved and developmental cancer therapies and identifies proprietary and related molecules for better patient treatment. For more information, visit www.ziopharm.com.

Forward-Looking Safe Harbor Statement:

This press release contains forward-looking statements for ZIOPHARM Oncology, Inc. that involve risks and uncertainties that could cause the Company's actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are based on current expectations, forecasts and assumptions that are subject to risks and uncertainties, which could cause actual outcomes and results to differ materially from these statements. Among other things, there can be no assurance that any of the Company's development efforts relating to its product candidates will be successful, or such product candidates will be successfully commercialized. Other risks that affect forward-looking information contained in this press release include the possibility of being unable to obtain regulatory approval of the Company's product candidates, the risk that the results of clinical trials may not support the Company's claims, and risks related to the Company's ability to protect its intellectual property and its reliance on third parties to develop its product candidates. The Company assumes no obligation to update these forward-looking statements, except as required by law.

ZIOP-G

SOURCE: ZIOPHARM Oncology, Inc.

ZIOPHARM Oncology, Inc.
Suzanne McKenna, 646-214-0703
smckenna@ziopharm.com
or
Argot Partners
Andrea Rabney, 212-600-1902
andrea@argotpartners.com

Amgen Presents Preclinical and Clinical Data from Oncology Programs Early Data Presented from Investigational Molecules that Target Apoptosis and Growth Regulation Pathways

Barry Sugarman — Tue, 15 Apr 2008 11:09:00 -0700

Press Release Detail
http://www.amgen.com/media/media_pr_detail.jsp?year=2008&releaseID=1129807

Apr. 15, 2008

Amgen Presents Preclinical and Clinical Data from Oncology Programs

See AMG 479 Release For Ewing's Sarcoma Below

Early Data Presented from Investigational Molecules that Target Apoptosis and Growth Regulation Pathways

Abstract Numbers: 3162, 1326, 3999, 2804, 4001, 3994

SAN DIEGO--(BUSINESS WIRE)--April 15, 2008--Amgen (NASDAQ:AMGN) today announced data generated by the company's robust oncology research and development programs in the areas of apoptosis (programmed cell death) and cell growth regulation. The data, presented at the American Association for Cancer Research (AACR) Annual Meeting in San Diego were from five preclinical studies evaluating anti-tumor activity, pharmacodynamics, and potential pre-clinical and clinical biomarkers for investigational molecules AMG 655, AMG 479 and AMG 102.

"We are excited to be pushing the boundaries of knowledge around known oncology pathways such as apoptosis and growth regulation by exploring new and innovative approaches to attack tumor cells," said David Chang, M.D., vice president, Global Oncology Development at Amgen. "While still early, we are pleased to be presenting a broad spectrum of data at this meeting reinforcing the biologic plausibility of targeting newly-discovered approaches to attack cancer via these pathways."

Targeting Apoptosis via Death Receptors

AMG 655 is an investigational fully human monoclonal antibody (mAb) agonist directed against death receptor 5 (DR5). AMG 655 is designed to activate caspases and induce apoptosis in sensitive tumor cells.

Apoptosis is a form of cell suicide in which a controlled sequence of biochemical events leads to cell death. In cancer, the dysregulation of apoptosis is critical in the development and survival of tumors. Apoptosis can be triggered by cell stress and DNA damage, but it also occurs normally during development of the body.

Data presented at AACR showed that, when combined with the chemotherapeutic agent gemcitabine, AMG 655 enhanced apoptosis in both in vitro, and in vivo, pancreatic cancer models. The combination of AMG 655 and gemcitabine was more effective in these models than either agent alone.

In another study, AMG 655 was combined with a chemotherapeutic agent (irinotecan or 5-fluorouracil (5-FU)) enhanced apoptosis relative to either agent alone in both in vitro and in vivo colon cancer cell models. AMG 655 is currently being tested against colorectal cancer in a Phase 1b/2 clinical trial.

In a third study, positron emission tomography (PET) was evaluated for its potential as a non-invasive method to measure receptor occupancy of DR5, the target of AMG 655. The preclinical results support the potential of using PET for imaging DR5 positive tumors and measuring receptor occupancy in patients. This imaging technology also is being applied to the study of other antibodies in the Amgen pipeline.

Targeting Growth Regulation in Cancer

AMG 479 is an investigational fully human monoclonal antibody that binds to insulin-like growth factor-1 receptor (IGF-1R) without cross-reacting with the closely related insulin receptor.

IGF-1 and IGF-2 activate the IGF-1R receptor, which is expressed in many human cancers. The expression of IGF-1 mediates tumor proliferation and reduces apoptosis and is associated with higher incidences and more aggressive progression of many common cancers.

Activation of these growth and survival pathways may allow tumor cells to resist the apoptosis-inducing activity of chemotherapy, radiation, and hormonal therapy and can increase cellular proliferation.

The preclinical data presented showed that AMG 479 inhibited more than 80 percent of IGF-1 induced growth activation in certain sarcoma cell line. Treatment of these cell lines with a combination of AMG 479 and cyclophosphamide resulted in significant (p=0.0020 vs. AMG 479, p=0.0002 vs. cyclophosphamide) tumor growth inhibition compared to either treatment alone. AMG 479 is currently in phase 2 Ewing's sarcoma trial.

AMG 102

AMG 102 is an investigational fully human monoclonal antibody that targets the action of anti-hepatocyte growth factor (HGF)/scatter factor (SF). HGF signaling through its receptor c-Met appears to play an important role in many types of human cancers.

The HGF/SF:c-Met pathway mediates a large number of normal activities in cells of epithelial origin - including proliferation, survival, migration, and invasion. The dysregulation of the HGF/SF:c-Met pathway appears to play an important role in many types of cancers, often leading to tumorigenesis and metastasis.

The data presented at AACR examined exploratory biomarkers that might be useful pharmacodynamic or patient enrichment markers for HGF/SF:c-Met therapies like AMG 102. Preclinical glioblastoma tumor xenograft models were treated with a single dose of AMG 102 ranging from 3- 300 ug IP. On days 3 and 7 after treatment initiation, plasma was harvested and levels of tumor-derived total human HGF, soluble human c-Met and CD44v6 (a c-Met associated protein) were quantified. Plasma samples from patients enrolled in the AMG 102 first-in-human trial were also examined. Total HGF and soluble c-Met levels were determined in plasma from patients in sequential dose cohorts (4-6 pts/cohort) that had been treated with AMG 102 at 0.5, 1, 3, 5, 10, or 20 mg/kg.

The study found that the treatment of tumor bearing preclinical models or cancer patients with AMG 102 gave rise to a dose-dependent increase in circulating HGF levels which suggests that monitoring HGF levels during treatment may serve as a biomarker for inhibition of the HGF/SF:c-Met pathway

About Amgen

Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives. To learn more about our pioneering science and our vital medicines, visit www.amgen.com.

Forward-Looking Statements

This news release contains forward-looking statements that are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission (SEC) reports filed by Amgen, including Amgen's most recent annual report on Form 10-K and most recent periodic reports on Form 10-Q and Form 8-K. Please refer to Amgen's most recent Forms 10-K, 10-Q and 8-K for additional information on the uncertainties and risk factors related to our business. Unless otherwise noted, Amgen is providing this information as of April 14, 2008 and expressly disclaims any duty to update information contained in this news release.

No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products after they are on the market. Our business may be impacted by government investigations, litigation and products liability claims. We depend on third parties for a significant portion of our manufacturing capacity for the supply of certain of our current and future products and limits on supply may constrain sales of certain of our current products and product candidate development.

In addition, sales of our products are affected by the reimbursement policies imposed by third-party payors, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments domestic and international trends toward managed care and health care cost containment as well as U.S. legislation affecting pharmaceutical pricing and reimbursement. Government and others' regulations and reimbursement policies may affect the development, usage and pricing of our products. In addition, we compete with other companies with respect to some of our marketed products as well as for the discovery and development of new products. We believe that some of our newer products, product candidates or new indications for existing products, may face competition when and as they are approved and marketed. Our products may compete against products that have lower prices, established reimbursement, superior performance, are easier to administer, or that are otherwise competitive with our products. In addition, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors and there can be no guarantee of our ability to obtain or maintain patent protection for our products or product candidates. We cannot guarantee that we will be able to produce commercially successful products or maintain the commercial success of our existing products. Our stock price may be affected by actual or perceived market opportunity, competitive position, and success or failure of our products or product candidates. Further, the discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations.

The scientific information discussed in this news release related to our product candidates is preliminary and investigative. Such product candidates are not approved by the U.S. Food and Drug Administration (FDA), and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidates. Only the FDA can determine whether the product candidates are safe and effective for the use(s) being investigated. Further, the scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the FDA for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses. Only the FDA can determine whether the products are safe and effective for these uses. Healthcare professionals should refer to and rely upon the FDA-approved labeling for the products, and not the information discussed in this news release.

CONTACT: Amgen, Thousand Oaks
Christine Regan, 617-359-1324 (media)
Arvind Sood, 805-447-1060 (investors)

SOURCE: Amgen

In Lab Study, Researchers Find Molecule That Disrupts Ewing’s Sarcoma Oncogene

Barry Sugarman — Sun, 13 Apr 2008 00:58:12 -0700

http://explore.georgetown.edu/news/?ID=32887

FOR IMMEDIATE RELEASE: April 13, 2008

CONTACT:	Karen Mallet 414-312-7085 km463@georgetown.edu

In Lab Study, Researchers Find Molecule That Disrupts Ewing’s Sarcoma Oncogene
SAN DIEGO – Researchers at Georgetown University Medical Center have found a small molecule they say can block the action of the oncogene that causes Ewing’s sarcoma, a rare cancer found in children and young adults. If further studies continue to prove beneficial, they say the novel agent could be the first targeted therapy to treat the disease, which can produce tumors anywhere in the body. The findings, presented today at the annual meeting of the American Association for Cancer Research (AACR) in San Diego, suggest that the unique way in which this molecule works – through a so-called protein-protein interaction – could provide a model upon which to design other therapies, says the study’s lead investigator, Jeffrey Toretsky, M.D., a pediatric oncology physician and researcher at Georgetown University’s Lombardi Comprehensive Cancer Center. “I think this holds really wonderful promise as a unique way of targeting fusion proteins,” he says. “People thought it wasn’t possible to have a small molecule that can bind between flexible proteins, but we have shown that it can be done.” This study was conducted in laboratory cells, so additional research is necessary before the novel agent can be tested in patients, Toretsky says. In vivo studies are now underway, he says. Ewing’s sarcoma is caused by the exchange of DNA between two chromosomes, a process known as a translocation. The new gene, known as EWS-FLI1, is created when the EWS gene on chromosome 22 fuses to the FLI1 gene on chromosome 11, and its product is the fusion protein responsible for cancer formation. In the United States, about 500 patients annually are diagnosed with the cancer, and they are treated with a combination of five different chemotherapy drugs. Between 60-70 percent of patients survive over time, but many have effects that linger from the therapy. Toretsky has long led research into the causes of, and treatments for, Ewing’s sarcoma. He and his laboratory colleagues were the first to make a recombinant EWS-FLI1 fusion protein. “We did this in order to find out if EWS-FLI1 might be binding with other cellular proteins,” he says. They found that, indeed, the fusion protein stuck to another protein, RNA helicase A (RHA), a molecule that forms protein complexes in order to control gene transcription. “We believe that when RHA binds to EWS-FLI1, the combination becomes more powerful at turning genes on and off,” says the study’s first author, Hayriye Verda Erkizan, Ph.D., a postdoctoral researcher in Toretsky’s lab who is presenting the study results at AACR. The researchers used a laboratory technique to keep RHA apart from the fusion protein, and found that both were important to cancer formation. Knowing that, they worked to identify the specific region on RHA that stuck to EWS-FLI1, and then collaborated with investigators in Georgetown’s Drug Discovery Program to find a molecule that would keep the two proteins separated. In other words, such an agent would stick to EWS-FLI1 in the very place that RHA bound to the fusion molecule. Using a library of small molecules loaned to Georgetown from the National Cancer Institute, the team of investigators tested 3,000 compounds to see if any would bind to immobilized EWS-FLI1 proteins. They found one that did, and very tightly. This was a wonderful discovery, Erkizan says, because the notion long accepted among scientists is that it is not possible to block protein-protein interactions given that the surface of these proteins are slippery, and much too flexible for a drug to bind to. “These are wiggly proteins yet this study shows that inhibition of protein-protein interactions with a small molecule is possible,” Toretsky says. This possibility means that fusion proteins, such as those produced in other sarcomas as well as diverse disorders, might be inhibited, he says. This is a different process than other drugs that have been shown to work against fusion proteins, such as Gleevec, which blocks the enzyme produced by the chromosomal translocation responsible for chronic myelogenous leukemia (CML). “Gleevec inhibits a single protein, while we are trying to block the binding of two proteins, and we are very enthusiastic about the results so far,” Toretsky says. Toretsky recently received a $750,000 Clinical Scientist Award in Translational Research from the Burroughs Wellcome Fund (BWF), which he will use to accelerate these translational efforts to help treat Ewing’s sarcoma, utilizing GUMC’s drug discovery program. The study was funded by the Children’s Cancer Foundation, Baltimore, MD., and Dani’s Foundation, Denver, CO. About Lombardi Comprehensive Cancer Center The Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Lombardi is one of only 39 comprehensive cancer centers in the nation, as designated by the National Cancer Institute, and the only one in the Washington, DC, area. For more information, go to http://lombardi.georgetown.edu. About Georgetown University Medical Center Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through our partnership with MedStar Health). Our mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing and Health Studies, both nationally ranked, the world-renowned Lombardi Comprehensive Cancer Center and the Biomedical Graduate Research Organization (BGRO), home to 60 percent of the university’s sponsored research funding. ###

Pharmamar Initiates A Phase II Study Of Yondelis® In Children With Recurrent Soft Tissue Sarcomas

Barry Sugarman — Mon, 17 Mar 2008 17:10:44 -0700

NEWS RELEASE

PHARMAMAR INITIATES A PHASE II STUDY OF YONDELIS®

IN CHILDREN WITH RECURRENT SOFT TISSUE SARCOMAS

http://www.pharmamar.com/en/press/news_release.cfm?newsReleaseID=178&year=2008

17 March 2008

Yondelis is being commercialized in the European Union for the treatment of advanced soft tissue sarcoma in adults.

Madrid, March 17th, 2008: PharmaMar announces the initiation of a Phase II multicenter study of Yondelis® (trabectedin) in children with recurrent rhabdomyosarcoma, Ewing´s sarcoma, or non-rhabdomyosarcomatous soft tissue sarcomas.

The study will determine a safe and tolerable dose of Yondelis in pediatric patients and assess the efficacy at that dose based on response rates. Additionally, toxicity and pharmacokinetics in these patients will be determined. A total of 60 patients aged 12 months to 21 years old will be accrued within approximately 2 years. Yondelis® will be administered as an intravenous infusion for 24 hours every 3 weeks.

The study is being carried out by the Childrens Oncology Group (COG) in centers of the USA and Canada. COG is an international research group with more than 200 hospitals that treat children with cancer in the United States, Canada, Australia, and Switzerland. The study is being managed by our co-development partner, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

The COG carried out a Phase I clinical trial to determine Yondelis® dose-limiting toxicities and maximum tolerated dose in children with refractory solid tumors, establishing the recommended dose for pediatric phase II trials, and characterizing the pharmacokinetics of Yondelis® in children. The study, published in Clinical Cancer Research in 2005 determined that Yondelis® is safe in children (Clinical Cancer Research Vol. 11, 672-677, Jan 2005).

Sylvain Baruchel, MD., Director of the New Agent and Innovative Therapy Program of the Hospital for Sick Children in Toronto, Canada, is the principal investigator of the current study and the already completed Phase I.

PharmaMar is committed to increasing the availability of medicines for children through promoting the pediatric development of its pipeline when appropriate. In line with this approach PharmaMar is planning to start new pediatric studies in the future.

Yondelis® is currently being developed by PharmaMar in partnership with Johnson & Johnson Pharmaceutical Research & Development L.L.C.. According to the licensing agreement, PharmaMar will market Yondelis® in Europe (including Eastern Europe) while Ortho Biotech Products, L.P., will market it in the U.S., and Janssen-Cilag will market it in the rest of the world.

About soft tissue sarcomas in children*

Soft tissue sarcomas are a heterogeneous group of malignancies of mesenchymal origin that develop at a variety of primary sites throughout the body. In children, soft tissue sarcomas generally are classified as either rhabdomyosarcomas (RMS) or non-rhabdomyosarcomas (non-RMS), with the non-RMS being further divided into multiple histologic subtypes which also include Ewing´s sarcoma. Rhabdomyosarcoma is the most common soft tissue sarcoma among children 0-14 years, representing nearly 50% of soft tissue sarcomas for this age range with an incidence rate of 4.6 per million.

According to the United States National Cancer Institute the incidence of soft tissue sarcomas in children and adolescents younger than 20 years of age was 11.0 per million, representing 7.4% of cancer cases for this age group.

*Source: National Cancer Institute, Surveillance Epidemiology and End Results (SEER) Cancer Incidence and Survival Among Children and Adolescents: United States SEER Program 1975-1995. ICCC IX, Soft Tissue Sarcomas. National Cancer Institute SEER Pediatric Monograph.

Important note

PharmaMar, based in Madrid, Spain, is a subsidiary of Grupo Zeltia (Spanish Stock Exchange, ZEL) that is quoted in the Spanish Stock Exchange since 1963 and the Spanish continuous market since 1998. Grupo Zeltia is currently part of the Ibex Nuevo Mercado (New Market).

This document is a press release, not a brochure. This document does not constitute nor is part of any offer or invitation to sell or issue any application of purchase, offer or shares subscription of the Society.
Likewise, this document nor its distribution is part or can be of base for any contract or investment decision and does not constitute any kind of recommendation in relation with the shares of the Company.

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For more information: www.pharmamar.com

Phase I/II Studies of IMC-A12 in Pediatric Cancer Patients Comence Enrollment

Barry Sugarman — Wed, 05 Mar 2008 11:12:37 -0800

Phase I/II Studies of IMC-A12 in Pediatric Cancer Patients Commence Enrollment

http://www.imclone.com/news.php

NEW YORK, Mar 05, 2008 (BUSINESSWIRE)-- ImClone Systems Incorporated (NASDAQ: IMCL), a global leader in the development and commercialization of novel antibodies to treat cancer, today announced that the initial stage of a series of Phase I/II clinical trials of IMC-A12, its anti-insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibody, in children with relapsed or refractory solid malignancies, has commenced patient enrollment. These pediatric trials of IMC-A12 are being carried out by the Children's Oncology Group (COG), an international research group that consists of more than 240 centers that treat children and adolescents with cancer in the United States, Canada, and other countries.

This study is the first of an initial stage of at least 10 Phase I and II clinical trials of IMC-A12 sponsored by the Cancer Therapy Evaluation Program (CTEP) of the Division of Cancer Treatment and Diagnosis (DCTD), National Cancer Institute (NCI), to commence patient enrollment. ImClone announced the selection of these proposals by NCI in September 2007.

The insulin-like growth factor (IGF) system plays a critical role in the development and progression of many types of cancer, including many pediatric-specific cancers. The initial Phase I study, which will be performed by the COG Phase I Consortium that includes 20 clinical COG sites in North America, will determine the optimal dose, side effects, pharmacology, and biological effects of IMC-A12 administered intravenously once each week to children and adolescents with relapsed or refractory solid cancers. Up to 38 patients are expected to be enrolled. Immediately upon determination of a recommended pediatric Phase II dose for IMC-A12, the antitumor activity of IMC-A12 will be evaluated in a much larger Phase II study in a larger number of COG sites. The Phase II study will evaluate the antitumor activity of IMC-A12 in multiple pediatric malignancies, including osteosarcoma, Ewing's sarcoma/peripheral primitive neuroectodermal tumor (PNET), rhabdomyosarcoma, Wilms' tumor, and others.

"We are pleased to initiate the first of a series of NCI-sponsored IMC-A12 trials and are particularly excited about this pediatric study, as it is one of the first such studies of an IGF-IR inhibitor ever undertaken in pediatric patients with cancer," said Eric K. Rowinsky, M.D., Chief Medical Officer and Executive Vice President of ImClone Systems. "Evaluations of new cancer therapies in children usually occur long after studies in adults and it is very gratifying to begin directed studies of IMC-A12 in both adult and pediatric patients at nearly the same time."

IMC-A12 is a fully human IgG1 monoclonal antibody. It is designed to specifically target the human IGF-1R, thereby inhibiting certain ligands known as IGFs I and II from binding to and activating the receptor. This action blocks a signaling pathway that enhances tumor cell proliferation and survival. In 2007, ImClone completed enrollment into two Phase I studies of IMC-A12, which demonstrated favorable safety and pharmacokinetic profiles, as well as preliminary evidence of antitumor activity as a single agent when administered either weekly or every two weeks. In addition to the studies of IMC-A12 in pediatric patients with advanced malignancies, Phase II studies of IMC-A12 in patients with advanced prostate and colorectal cancers have begun to enroll patients.

About ImClone's NCI-sponsored IMC-A12 Trials

In September 2007, the CTEP of the DCTD, NCI selected 10 proposals for Phase I and II clinical trials of ImClone's IMC-A12, and several other proposals have been selected since that time. The selection of the proposed trials followed NCI's solicitation for specific disease-directed studies among NCI investigators at academic institutions, clinical trial consortia and NCI-sponsored oncology cooperative clinical trial groups in the U.S. The selected trials represent the first stage of clinical evaluations of IMC-A12 sponsored by CTEP, NCI under a Clinical Trials Agreement between ImClone Systems and DCTD, NCI to facilitate the clinical development of IMC-A12. Both randomized and nonrandomized Phase II trials sponsored by CTEP will explore the clinical activity, pharmacology and biological effects of IMC-A12 as a single agent or combined with other relevant anticancer agents in a wide range of malignancies including breast, lung, pancreas and liver cancers, as well as both adult and pediatric sarcomas. In addition, Phase I/II studies will evaluate the safety, pharmacology, anticancer activity and biological effects of IMC-A12 in children and adolescents with cancer, as well as in combination with other novel targeting agents in which there is a specific rationale for combined use.

About ImClone Systems

ImClone Systems Incorporated is a fully integrated biopharmaceutical company committed to advancing oncology care by developing and commercializing a portfolio of targeted biologic treatments designed to address the medical needs of patients with a variety of cancers. The Company's research and development programs include growth factor blockers and angiogenesis inhibitors. ImClone Systems' headquarters and research operations are located in New York City, with additional administration and manufacturing facilities in Branchburg, New Jersey. For more information about ImClone Systems, please visit the Company's web site at

http://www.imclone.com

Certain matters discussed in this news release may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and the Federal securities laws. Although the company believes that the expectations reflected in such forward-looking statements are based upon reasonable assumptions it can give no assurance that its expectations will be achieved. Forward-looking information is subject to certain risks, trends and uncertainties that could cause actual results to differ materially from those currently expected. Many of these factors are beyond the company's ability to control or predict. Important factors that may cause actual results to differ materially and could impact the company and the statements contained in this news release can be found in the company's filings with the Securities and Exchange Commission, particularly those factors identified as "risk factors" in the Company's most recent annual report of Form 10-K and in its quarterly reports on Form 10-Q and current reports on Form 8-K. For forward-looking statements in this news release, the company claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. The company assumes no obligation to update or supplement any forward-looking statements whether as a result of new information, future events or otherwise.

SOURCE: ImClone Systems Incorporated

ImClone Systems Incorporated
Corporate Communications
Tracy Henrikson, 908-243-9945
MEDIA@IMCLONE.COM
or
Rebecca Gregory, 646-638-5058
Corporate Communications

Myeloablative therapy with autologous stem cell rescue for patients with Ewing sarcoma

Barry Sugarman — Sun, 10 Feb 2008 22:35:05 -0800

Bone Marrow Transplantation advance online publication 4 February 2008; doi: 10.1038/bmt.2008.2

Myeloablative therapy with autologous stem cell rescue for patients with Ewing sarcoma

S L Gardner¹, J Carreras², C Boudreau³, B M Camitta⁴, R H Adams⁵, A R Chen⁶, S M Davies⁷, J R Edwards⁸, A C Grovas⁹, G A Hale¹⁰, H M Lazarus¹¹, M Arora¹², P J Stiff¹³ and M Eapen²

¹Department of Pediatric Oncology, New York University, New York, NY, USA
²Statistical Center, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA
³Department of Statistics & Actuarial Science, University of Waterloo, Waterloo, Ontario, Canada
⁴Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
⁵BMT Internal Medicine, Mayo Clinic Arizona, Phoenix, AZ, USA
⁶Department of Pediatric Oncology, John Hopkins Hospital, Baltimore, MD, USA
⁷Department of Bone Marrow Transplantation, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
⁸Department of Bone Marrow Transplantation, Florida Hospital Cancer Institute, Orlando, FL, USA
⁹Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA
¹⁰Department of Bone Marrow Transplantation, St Jude Children's Research Hospital, Memphis, TN, USA
¹¹Department of Hematology/Oncology, University Hospitals of Cleveland, Cleveland, OH, USA
¹²Department of Hematology/Oncology, University of Minnesota, Minneapolis, MN, USA
¹³Department of Bone Marrow Transplantation, Loyola University Medical Center, Maywood, IL, USA

Correspondence: Dr M Eapen, Statistical Center, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. E-mail: meapen@mcw.edu

Received 20 August 2007; Revised 19 December 2007; Accepted 20 December 2007; Published online 4 February 2008.

The aim of this study was to identify risk factors associated with PFS in patients with Ewing sarcoma undergoing ASCT; 116 patients underwent ASCT in 1989–2000 and reported to the Center for International Blood and Marrow Transplant Research. Eighty patients (69%) received ASCT as first-line therapy and 36 (31%), for recurrent disease. Risk factors affecting ASCT were analyzed with use of the Cox regression method. Metastatic disease at diagnosis, recurrence prior to ASCT and performance score <90 were associated with higher rates of disease recurrence/progression. Five-year probabilities of PFS in patients with localized and metastatic disease at diagnosis who received ASCT as first-line therapy were 49% (95% CI 30–69) and 34% (95% CI 22–47) respectively. The 5-year probability of PFS in patients with localized disease at diagnosis, and received ASCT after recurrence was 14% (95% CI 3–30). PFS rates after ASCT are comparable to published rates in patients with similar disease characteristics treated with conventional chemotherapy, surgery and irradiation suggesting a limited role for ASCT in these patients. Therefore, ASCT if considered should be for high-risk patients in the setting of carefully controlled clinical trials.

Keywords:

autologous transplant, Ewing sarcoma, PFS

Early Stage Drug Shows Promise Against Cancer Cells from Young Patients

Barry Sugarman — Sun, 28 Oct 2007 20:35:06 -0700

http://www.ncri.org.uk/ncriconference/info/releases/pr5.pdf

Early Stage Drug Shows Promise
Against Cancer Cells from Young Patients

A NEW drug has shown promising pre-clinical activity
against cells from several types of children’s cancers,
scientists reveal at the National Cancer Research
Institute Conference in Birmingham today (Tuesday).
http://www.ncri.org.uk/ncriconference
Scientists from Cancer Research UK’s Paterson
Institute at the University of Manchester have shown
in laboratory tests that the drug RH1 can kill tumour
cells from neuroblastoma, osteosarcoma and Ewing’s
sarcoma, three types of childhood and adolescent cancer
that are often resistant to current types of chemotherapy.
Despite increases in survival rates for childhood cancers,
new drugs are needed to combat drug resistance seen in
current treatments. On the strength of these pre-clinical
results, the researchers are planning a phase 1 trial for
the drug involving children with cancer.
All cells have natural suicide mechanisms that become
active when cells are damaged or grow uncontrollably.
In cancer cells, this suicide mechanism switches off or
becomes faulty and treatment is needed to encourage
the process.
The researchers – based at the Paterson Institute for
Cancer Research Manchester ( http://www.mcrc.manchester.ac.uk ) and the Royal Manchester
Children’s Hospital ( http://www.cmmc.nhs.uk ) – found in their pre-clinical study
that even very low doses of RH1 could increase cancer
cell death by around 50 per cent when compared with
untreated cells.
RH1’s activity is greatly enhanced by an enzyme, DTdiaphorase
(DTD), which is found in higher quantities
in many adult tumours, including lung, liver and breast
cancers, and the drug has recently completed phase 1
studies in adults.
Dr Guy Makin, the study’s lead researcher from the
Paterson Institute ( http://www.paterson.man.ac.uk ) said: “We are very excited that we
have been able to work with a new drug that has only
just completed an adult phase 1 study. RH1 is a very
potent agent and our pre-clinical results suggest that
it could be effective against childhood tumours that
express DTD. We hope that this will be just the first
of many new agents that we can show are useful for
treating childhood cancer.”
The planned trial would be the first for a drug tested
for children through Cancer Research UK’s drug
development office.
Dr Bruce Morland, chairman of the Children’s Cancer and
Leukaemia Group (CCLG, http://www.ukccsg.org ), who were instrumental in the
selection of RH1 for evaluation, said: “Survival rates for
children with cancer are already high at 75 per cent. But
in many cases, patients become resistant to their drugs
and need new options.
“This is an exciting moment in the history of the CCLG.
Our increasingly close relationship with the Cancer
Research UK drug development office means new
potentially promising anticancer drugs can be tested in
children at a much earlier point in their development.
In this way we hope that new, effective drugs are
introduced in the fight against children’s cancer at
the earliest opportunity, saving even more lives in the
process.”
RH1 was synthesised from MeDZQ, an anti-tumour
chemical that selectively kills cancer cells. The RH1
compound was manufactured by scientists to be a watersoluble
version of MeDZQ, making it more effective as a
drug for potential clinical use.
Dr Sally Burtles, Cancer Research UK’s ( http://www.cancerresearchuk.org ) director of drug
development, said: “Helping more children survive
cancer by finding new treatments is a top priority for
the charity. Currently, not many drugs are developed
specifically for children so it’s great news that the drug is
showing such encouraging effects in preclinical studies.
We hope this type of drug development will continue
and help improve the treatment of childhood cancer
patients.”

How to contact the Manchester Cancer Research Centre:
Manchester Cancer Research Centre
The University of Manchester
Wilmslow Road
Withington
Manchester
M20 4BX
England
Tel: +44 0161 446 3156 (From the USA, 011-44-161-446-3156)
Fax: +44 0161 446 3109
email mcrc@manchester.ac.uk

Central Manchester and Manchester Children's University Hospitals NHS Trust
Trust Headquarters, Cobbett House
Manchester Royal Infirmary
Oxford Road
Manchester
M13 9WL
Tel: +44 (0)161 276 1234 (From the USA, 011-44-161-276-1234
Fax: +44 (0)161 273 6211 (Trust HQ)

Roche Announces Positive Results in Solid Tumors Using Human Monoclonal Antibody against IGF-1R (R1507)

Barry Sugarman — Tue, 23 Oct 2007 20:47:16 -0700

http://www.rocheusa.com/newsroom/current/2007/pr2007102302.html

October 23, 2007 -- Nutley N.J.

Roche Announces Positive Results in Solid Tumors Using Human Monoclonal Antibody against IGF-1R (R1507)

Today, Roche announced positive results from a Phase I trial of R1507, a human monoclonal antibody to target IGF-1R (insulin-like growth factor receptor), in patients with solid tumors. IGF-1 is one of the most potent natural activators of the AKT and MAPK signaling pathways, which promote cell growth and cell survival. The IGF-1R pathway has also been shown to have an important role in mediating the resistance to cytotoxic drugs and EGFR/HER2-targeted agents. The results were reported during the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held in San Francisco.

Study Results
In the Phase I study, R1507 was administered by intravenous infusion. Nine of 34 adult patients with advanced solid tumors experienced disease stabilization. Four of the seven heavily pretreated patients with Ewing’s sarcoma demonstrated clinical benefit with two of these patients achieving durable, objective partial responses.

Once a week administration of R1507 was well tolerated with very few side effects. Treatment with R1507 was not associated with the typical side-effects normally observed with cancer therapy (e.g., low blood counts, infection, hair loss, severe nausea and vomiting). The most frequent side effects observed were fatigue, anorexia and weight loss, symptoms that are commonly observed in patients with advanced cancer.

“We are very encouraged by these early results with R1507 in patients with refractory Ewing’s sarcoma,” said Kapil Dhingra, MD, Head, Oncology Disease Biology Area at Roche. “As a result, we have given this program a very high priority as we believe this molecule has the potential to be very beneficial in treating patients with sarcoma as well as a variety of other solid tumors.”

The antibody (R1507) was initially developed under Roche’s broad antibody development collaboration with Genmab, which began in 2001.

The Phase I study is being conducted at four sites in the U.S., including the University of Colorado Cancer Center (Aurora, CO), The University of Texas M.D. Anderson Cancer Center (Houston, TX), Cancer Institute of New Jersey (New Brunswick, NJ) and The Institute for Drug Development (San Antonio, TX). R1507 has also been investigated in 26 patients on a three week schedule in the Phase I study. This treatment schedule was also generally well tolerated with a side effect profile similar to the weekly schedule.

“This drug attacks the IGF pathway and may provide a new class of drugs to treat a variety of cancers, including breast, prostate, colon, melanoma, myeloma and a variety of sarcomas, which could greatly add to the way that we currently treat these patients,” says Stephen Leong, M.D., assistant professor of Medical Oncology at the University of Colorado Cancer Center and lead author of the abstract.

Razelle Kurzrock, MD, investigator at the M.D. Anderson Cancer Center and the senior author of the abstract, noted that some of the responses were very impressive. For instance, one 28 year-old Ewing’s sarcoma patient with large tumors unresponsive to many other treatments showed dramatic tumor shrinkage within six weeks, without side effects. "This is one of the best responses I've seen in over 20 years of oncology experience," stated Dr. Kurzrock.

Based on these initial results with R1507, Roche plans to conduct additional trials and work with a global consortium of sarcoma experts, including the Sarcoma Alliance for Research through Collaboration (SARC). “We are very excited about our collaboration with SARC, which represents a new approach to sarcoma clinical trials, and we look forward to combining our expertise with that our colleagues at SARC to expedite new sarcoma treatments,” added Dhingra.

“We are excited to be partnering with Roche on the development of a new treatment against an important target, which could result in a potential breakthrough treatment for sarcoma as well as other cancers,” said Laurence Baker, DO, professor of Medicine and Pharmacology at the University of Michigan and the Executive Director, SARC. “With Roche’s considerable expertise in oncology and SARC’s vast network of physicians and institutions, we look forward to determining the potential of R1507 in this important disease area.”

About Ewing’s Sarcoma
The Ewing’s family of tumors (EFT) includes primary tumors of bone (classic Ewing’s sarcoma, primitive neuroectodermal tumor, and Askin tumor) and extraosseous primary tumors {National Cancer Institute}. Studies using immunohistochemical markers, cytogenetics, molecular genetics, and tissue culture indicate that these tumors are all derived from the same primordial stem cell. EFTs account for 4 percent of childhood and adolescent malignancies. The estimated incidence (US) is approximately 300 new cases per year. The median age for patients with EFT is 15 years and more than 50 percent of patients are adolescents. There is a slight male predominance and the lower limbs are affected in 40 percent of the patients.

Approximately 20 to 30 percent of the patients with ETB have overt metastases at the time of diagnosis. However, outcomes for patients with metastatic disease have improved little during the last 20 years. Approximately 25-30 percent survival could be achieved with current therapies for patients who present with metastatic disease at initial diagnosis.

About Roche
Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. pharmaceuticals headquarters of the Roche Group, one of the world’s leading research-oriented healthcare groups with core businesses in pharmaceuticals and diagnostics. For more than 100 years in the U.S., Roche has been committed to developing innovative products and services that address prevention, diagnosis and treatment of diseases, thus enhancing people's health and quality of life. An employer of choice, in 2007 Roche was named Top Company of the Year by Med Ad News and one of the Top 20 Employers (Science magazine). In 2006, Roche was ranked the No. 1 Company to Sell For (Selling Power), and one of AARP’s Top Companies for Older Workers, and in 2005, Roche was named one of Fortune magazine’s Best Companies to Work For in America. For additional information about the U.S. pharmaceuticals business, visit our websites: http://www.rocheusa.com or www.roche.us.

About SARC
The purpose of the Sarcoma Alliance for Research through Collaboration (SARC) is to engage all appropriate and necessary resources to cure and prevent sarcoma. SARC brings together expert sarcoma researchers and clinicians from 29 centers of excellence in the United States. SARC by the charter, promotes international collaboration in sarcoma clinical trials through is association with European sarcoma experts. SARC is unique as a clinical trial organization in that its trials at the inception include pediatric and medical patients with sarcoma, because sarcomas affect people of all ages. SARC is a 501c3, non-profit organization that is headquartered in Ann Arbor, Michigan.

###
Contacts: 973-562-2699

Oncolytics Biotech Inc. Commences Patient Enrollment in U.S. Phase II Sarcoma Clinical Trial

Barry Sugarman — Wed, 27 Jun 2007 23:52:48 -0700

Oncolytics Biotech Inc. Commences Patient Enrolment in U.S. Phase II Sarcoma Clinical Trial

http://www.integratir.com/newsrelease.asp?news=2130983233&ticker=T.ONC&lang=EN&ny=on

6/27/2007 2:00:00 AM ET

CALGARY, AB, --- June 27, 2007 - Oncolytics Biotech Inc. (“Oncolytics”) (TSX:ONC, NASDAQ:ONCY) announced today that patient enrolment has commenced in its U.S. Phase II trial to evaluate the intravenous administration of REOLYSIN® in patients with various sarcomas that have metastasized to the lung. Patients are being enrolled at the Montefiore Medical Center/Albert Einstein College of Medicine in the Bronx, New York, the University of Michigan Comprehensive Cancer Center in Ann Arbor, and the Cancer Therapy and Research Center, Institute for Drug Development in San Antonio, Texas.

“The initiation of this trial represents an important milestone for the Company,” said Dr. Brad Thompson, President and CEO of Oncolytics. “We are now treating patients with advanced cancers in Phase II clinical trials in the U.S. and the U.K., with additional Phase II trials expected to begin before the end of the year. These trials are expected to yield information that will guide the late stage clinical development program for REOLYSIN®.”

The trial (REO 014) is a Phase II, open-label, single agent study whose primary objective is to measure tumour responses and duration of response, and to describe any evidence of antitumour activity of intravenous, multiple dose REOLYSIN® in patients with bone and soft tissue sarcomas metastatic to the lung. REOLYSIN® will be given intravenously to patients at a dose of 3x10(10) TCID(50) for five consecutive days. Patients may receive additional five-day cycles of therapy every four weeks for a maximum of eight cycles. Up to 52 patients will be enrolled in the study.

Eligible patients must have a bone or soft tissue sarcoma metastatic to the lung deemed by their physician to be unresponsive to or untreatable by standard therapies. These include patients with osteosarcoma, Ewing sarcoma family tumours, malignant fibrous histiocytoma, synovial sarcoma, fibrosarcoma and leiomyosarcoma.

“There are very few treatment options for patients with bone or soft tissue sarcomas,” said Dr. Matt Coffey, Oncolytics’ Chief Scientific Officer. “Our decision to choose this indication is based on the observed activity of REOLYSIN® against sarcomas in both preclinical and clinical studies.”

About Oncolytics Biotech Inc.
Oncolytics is a Calgary-based biotechnology company focused on the development of oncolytic viruses as potential cancer therapeutics. Oncolytics’ clinical program includes a variety of Phase I and Phase II human trials using REOLYSIN®, its proprietary formulation of the human reovirus, alone and in combination with radiation or chemotherapy. For further information about Oncolytics, please visit www.oncolyticsbiotech.com

This press release contains forward-looking statements, within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements, including the Company’s expectations related to the U.S. Phase II sarcoma clinical trial and the Company’s belief as to the potential of REOLYSIN® as a cancer therapeutic, involve known and unknown risks and uncertainties, which could cause the Company’s actual results to differ materially from those in the forward-looking statements. Such risks and uncertainties include, among others, the availability of funds and resources to pursue research and development projects, the efficacy of REOLYSIN® as a cancer treatment, the tolerability of REOLYSIN® outside a controlled test, the success and timely completion of clinical studies and trials, the Company’s ability to successfully commercialize REOLYSIN®, uncertainties related to the research and development of pharmaceuticals and uncertainties related to the regulatory process. Investors should consult the Company’s quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties relating to the forward-looking statements. Investors are cautioned against placing undue reliance on forward-looking statements. The Company does not undertake to update these forward-looking statements.

FOR FURTHER INFORMATION PLEASE CONTACT:
Oncolytics Biotech Inc.
Cathy Ward
210, 1167 Kensington Cr NW
Calgary, Alberta T2N 1X7
Tel: 403.670.7377
Fax: 403.283.0858
cathy.ward@oncolytics.ca

The Equicom Group
Nick Hurst
325, 300 5th Ave. SW
Calgary, AB, T2P 3C4
Tel: 403.538.4845
Fax: 403.237.6916
nhurst@equicomgroup.com

The Investor Relations Group
Erika Moran
11 Stone St, 3rd Floor
New York, NY 10004
Tel: 212.825.3210
Fax: 212.825.3229
emoran@investorrelationsgroup.com

Hyperthermia Plus Chemotherapy Nearly Doubles Disease-Free Survival Compared to Chemotherapy Alone for Sarcoma Cancer Patients

Barry Sugarman — Tue, 05 Jun 2007 22:43:26 -0700

Hyperthermia Plus Chemotherapy Nearly Doubles Disease-Free Survival Compared to Chemotherapy Alone for Sarcoma Cancer Patients

http://www.bsdmc.com/press.html?id=242&s=45e1308f965138c8ef29013929e90c15

SALT LAKE CITY---June 4, 2007--- BSD Medical Corp. (AMX:BSM) announced today that the results of a 340 patient randomized Phase III clinical trial testing the benefit of adding hyperthermia therapy to chemotherapy were presented at the annual American Society of Clinical Oncology (ASCO) conference underway in Chicago, Illinois. According to the results of this clinical study, which was conducted at nine major European cancer treatment institutions and at Duke University Medical Center in the USA, both disease-free survival time and local progression free survival time for patients with locally advanced, high-grade soft tissue sarcomas nearly doubled when hyperthermia therapy was added to chemotherapy, as compared to patients who received chemotherapy alone.

The patients enrolled in this clinical study were very ill, with high-grade (II/III) soft tissue sarcomas and were at significant risk of local failure and metastasis. The patients were randomly assigned to receive either chemotherapy alone or chemotherapy combined with hyperthermia therapy. The patient characteristics were well balanced between these two groups. Their treatments were administered in 4 cycles every 3 weeks before and after surgery and radiation therapy. For patients who received both hyperthermia therapy and chemotherapy the median disease free survival was 31.7 months, compared to 16.2 months for those who received chemotherapy alone (p=0.004), a 95% increase. The median local progression free survival rate was estimated at 45.3 months for patients who received chemotherapy plus hyperthermia therapy, compared to 23.7 months for patients who received chemotherapy alone (p=0.01), a 91% increase.

The study was conducted under the direction of the European Society of Hyperthermic Oncology (ESHO RHT-95) and the European Organization for Research and Treatment of Cancer (EORTC 62961). Rolf Issels, MD PhD of the Munich University Medical School in Germany, was the principal investigator. Duke University was a participant in the international study listed on the National Cancer Institute's website at http://www.cancer.gov/clinicaltrials/EORTC-62961 under the NCI number NCT00003052.

All hyperthermia treatments performed in the study were conducted using BSD-2000 hyperthermia systems developed and produced by BSD Medical Corp. The BSD-2000 hyperthermia therapy system non-invasively delivers precision focused hyperthermia therapy to cancerous tumors, including tumors located deep in the body. The BSD-2000 is a recipient of the Frost and Sullivan Technology Innovation of the Year Award for cancer therapy devices.

About BSD Medical

BSD Medical Corp. is the leading developer of systems used to deliver hyperthermia therapy for the treatment of cancer. Hyperthermia therapy is used to kill cancer directly and increase the effectiveness of companion radiation treatments. Research has also shown promising results from the use of hyperthermia therapy in combination with chemotherapy, and for tumor reduction prior to surgery. For further information visit BSD Medical's website at www.BSDMedical.com or BSD's patient website at www.treatwithheat.com.

Statements contained in this press release that are not historical facts are forward-looking statements, as defined in the Private Securities Litigation Reform Act of 1995. All forward-looking statements are subject to risks and uncertainties detailed in the Company's filings with the Securities and Exchange Commission.

First report that apoptotic and anti-angiogenic therapies work better together than alone

Barry Sugarman — Sat, 18 Nov 2006 11:06:22 -0800

http://www.eurekalert.org/pub_releases/2006-11/eofr-frt110906.php

Public release date: 10-Nov-2006

Contact: Emma Mason
wordmason@mac.com
44-077-112-96986
European Organisation for Research and Treatment of Cancer

First report that apoptotic and anti-angiogenic therapies work better together than alone

Prague, Czech Republic: American researchers have found that giving a combination of imantanib (Glivec [1]) and a drug that induces cell death (apoptosis) was better at inhibiting the growth of Ewing's sarcoma in mice than either therapy on its own.

Imantanib works by preventing the creation of new blood vessels to supply the growing tumour (anti-angiogenesis) and the researchers believe that this is the first report of synergy between apoptosis and anti-angiogenic therapy in pre-clinical work.

Professor Andrea Hayes-Jordan reported to the EORTC-NCI-AACR [2] Symposium on Molecular Targets and Cancer Therapeutics in Prague today (Friday 10 November) that treating sarcoma cells with imantanib inhibited a growth factor called PDGFR-beta. This had the effect of increasing the sensitivity of the cells to a drug called tumour necrosis factor-related apoptosis-inducing ligand (TRAIL).

Prof Hayes-Jordan, assistant professor of surgery and pediatrics at the MD Anderson Cancer Center, Houston, USA, said: "When I treated the tumour cells with imantanib, the anti-angiogenic drug, the receptors for TRAIL, the apoptotic drug, increased, thus increasing the efficacy of TRAIL. This was supported by the mouse studies, which showed increased inhibition of pulmonary metastases and primary tumour growth when both were used simultaneously. These findings are important because, if it proves to be effective in humans, it would be well tolerated and have significantly fewer side effects than traditional cytotoxic therapy. Also, at present, we have no effective chemotherapy for pulmonary metastases – the only effective treatment is surgery – so this would give us another option."

Prof Hayes-Jordan hopes to investigate the dual therapy in humans in a clinical trial within 12-18 months.

###

External Beam Radiation With Intratumoral Injection Of Dendritic Cells As Neo-Adjuvant Treatment for Sarcoma

Barry Sugarman — Mon, 25 Sep 2006 08:40:14 -0700

http://www.clinicaltrials.gov/ct/show/NCT00365872?order=37

External Beam Radiation With Intratumoral Injection Of Dendritic Cells As Neo-Adjuvant Treatment for Sarcoma

This study is currently recruiting patients.
Verified by H. Lee Moffitt Cancer Center and Research Institute August 2006
Sponsors and Collaborators:     H. Lee Moffitt Cancer Center and Research Institute
Cancer Treatment Research Foundation
Information provided by:     H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:     NCT00365872

Purpose

This is a Phase II study using a combination of external beam radiation with intratumoral injection of dendritic cells (white blood cells) as neo-adjuvant treatment for patients with high-risk soft tissue sarcoma. The purpose is to determine if an injection of the patient’s own immune related white blood cells into their tumor will strengthen the immune system to fight against their cancer.

Pre-treatment tests include a blood draw for anti-tumor immune response and Hepatitis B, Hepatitis C, HIV tests. Labs are drawn for baseline immunity assays; pre-treatment biopsy with collection of tumor cells, immunological studies, surgical specimen and post-therapy immunity assays.

Conventional therapy on day 1 is the external beam radiation which will be delivered in 25 equal fractions – daily for 5 days (M-F) over a 5-week period. Experimental therapy consists of leukapheresis which is the separation and removal of leukocytes from withdrawn blood, frozen for later use. There will be four DC injections occurring during the course of the external beam radiation therapy.

DCs will be labeled (with a radioisotope) and injected intratumorally before surgery. You will be randomized into one of three groups. One group will receive injection of labeled DCs 72 hrs before surgery, second group – 48 hrs, and third group 24 hrs before surgery. On day 50 of treatment,surgery will be performed to remove the tumor.

Results will be correlated with the level of specific immune response. If the experimental treatment causes a measurable change in the immune blood tests, there will be office visits, every 3 months for 2 years. In the longer term, there will be office visits at 6 month intervals for the third year, and yearly thereafter. A CT scan of chest and MRI scan of extremity will be performed at every office visit.
Condition     Intervention     Phase
Soft Tissue Sarcoma
    Vaccine: Dendritic cell injections
Procedure: Radiation therapy
Procedure: Surgery for tumor removal
    Phase II

MedlinePlus related topics: Soft Tissue Sarcoma
Genetics Home Reference related topics: Soft Tissue Sarcoma

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Official Title: Combination of External Beam Radiation With Intratumoral Injection of Dendritic Cells as Neo-Adjuvant Treatment of High-Risk Soft Tissue Sarcoma Patients
Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:
Primary Outcomes: Determine if combined neo-adjuvant treatment with apoptosis-inducing therapy (gamma-irradiation) plus intratumoral DC administration will induce a T lymphocyte immune response specific for soft tissue sarcoma associated antigens.; Study the functional activity of T cells, as well as the presence, and function of DCs in patients treated with combined administration of apoptosis-inducing agents and DCs.; Assess the toxicity of the investigational treatment, and the primary tumor responses.; Analysis of DC migration will compare the ratio of radioactive count within lymph nodes and the tumor site to the background counts.
Expected Total Enrollment: 22

Study start: June 2006

This is a Phase II study using a combination of external beam radiation with intratumoral injection of dendritic cells (white blood cells) as neo-adjuvant treatment for patients with high-risk soft tissue sarcoma. The purpose is to determine if an injection of the patient’s own immune related white blood cells into their tumor will strengthen the immune system to fight against their cancer.

Pre-treatment test will consist of a blood draw for anti-tumor immune response and Hepatitis B, Hepatitis C, HIV tests. A biopsy with collection of tumor cells. Assays (ELISPOT and flow cytometry) to test for the intended anti-tumor cell T cell response will be performed on biopsy specimens as well as standard pathology department review of specimens for diagnosis and assessment of necrosis and apoptosis. Labs are also drawn for surgical specimens and post-therapy immunity assays.

Prior to commencing therapy, a procedure called leukapheresis (peripheral blood mononuclear cell) isolation will be conducted and twenty-four hours prior to intended injection, the dendritic cells will be harvested and assessed for quality control. Prior to injection (the clinical target is the gross tumor), history and physical examination will be performed. Toxicity will be assessed according to CTC criteria. The plan will be to inject the entire dendritic cell product evenly throughout the tumor.

Conventional therapy consists of external beam radiation therapy, 25 fractions from day 1-33 administered Monday through Friday only. The experimental therapy, dendrite cell (DC) injections will occur during the course of the external beam radiation therapy. DC injections will be prepared from frozen white blood cells and injected at four intervals on day 12, 19, 26, and day 33.

DCs will be labeled (with a radioisotope) and injected intratumorally before surgery. You will be randomized into one of three groups. One group will receive injection of labeled DCs 72 hrs before surgery, second group – 48 hrs, and third group 24 hrs before surgery. Surgery will occur on day 50 for tumor removal.

If the experimental treatment causes a measurable change in the immune blood tests, there will be office visits, every 3 months for 2 years. In the longer term, there will be office visits at 6 month intervals for the third year, and yearly thereafter. A CT scan of chest and MRI scan of extremity will be performed at every office visit.

Eligibility
Genders Eligible for Study: Both
Criteria

Inclusion Criteria:

    * Histologically diagnosed high-grade (intermediate or high grade) soft tissue sarcoma of clinical and radiographic histological lineage.
    * Musculoskeletal tumor in extremities, trunk or chest wall.
    * Primary tumor or isolated locally recurrent tumor greater than 5 cm in diameter.
    * Clinical Stage T2N0M0 or T3N0M0
    * Patient is not a candidate for neoadjuvant chemotherapy.
    * Performance status ECOG 0 or 1.
    * No steroid therapy within 4 weeks of first dendritic cell administration.
    * No coagulation disorder.
    * Patient’s written informed consent.
    * No contraindication to resection.
    * Adequate organ function (measured within a week of beginning treatment).
    * WBC > 3,000/mm to the third power and ANC >1500/mm to the third power
    * Platelets > 100,000/mm to the third power
    * Hematocrit > 25%
    * Bilirubin < 2.0 mg/dL
    * Creatinine < 2.0 mg/dL, or creatinine clearance > 60 mL/min

Exclusion Criteria:

    * Retroperitoneal location.
    * Gastrointestinal stromal tumor (GIST).
    * Demonstrated metastatic disease.
    * Prior radiation therapy if the current tumor is locally recurrent after prior resection.
    * Concurrent treatment with any anticancer agent other than radiation as dictated by the protocol.
    * Bleeding disorder.
    * H.I.V. infection or other primary immunodeficiency disorder.
    * Ongoing systemic therapy with immunosuppressant drugs (e.g. corticosteroids, azathioprine, cyclosporin, methotrexate).
    * Any serious ongoing infection.
    * Pregnant or lactating women -- Patients in reproductive age must agree to use contraceptive methods for the duration of the study (a pregnancy test will be obtained before treatment).
    * ECOG performance status of 2, 3 or 4.

Location and Contact Information
Please refer to this study by ClinicalTrials.gov identifier NCT00365872

Mary N Dunn, CRN      813-745-8356    dunnmn@moffitt.usf.edu

Florida
      H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, 33612, United States; Completed

      H Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, 33612, United States; Recruiting

Study chairs or principal investigators

Scott Antonia, M.D., Principal Investigator, H. Lee Moffitt Cancer Center and Research Institute

More Information

Active Clinical Trials at Moffitt Cancer Center

Study ID Numbers: MCC-14497
Last Updated: August 18, 2006
Record first received: August 17, 2006
ClinicalTrials.gov Identifier: NCT00365872
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2006-09-25

Impact of High-Dose Busulfan Plus Melphalan As Consolidation in Metastatic Ewing Tumors: A Study by the Société Française des Cancers de l'Enfant

Barry Sugarman — Sun, 17 Sep 2006 18:07:59 -0700

http://www.jco.org/cgi/content/abstract/24/24/3997

Impact of High-Dose Busulfan Plus Melphalan As Consolidation in Metastatic Ewing Tumors: A Study by the Société Française des Cancers de l'Enfant

Journal of Clinical Oncology, Vol 24, No 24 (August 20), 2006: pp. 3997-4002
© 2006 American Society of Clinical Oncology
DOI: 10.1200/JCO.2006.05.7059

Odile Oberlin, Annie Rey, Anne Sophie Desfachelles, Thierry Philip, Dominique Plantaz, Claudine Schmitt, Emmanuel Plouvier, Odile Lejars, Hervé Rubie, Philippe Terrier, Jean Michon

From the Departments of Paediatric Oncology, Biostatistics, and Pathology, Institut Gustave Roussy, Villejuif; Department of Paediatric Oncology, Centre Oscar Lambret, Lille; Department of Paediatric Oncology, Centre Léon Bérard, Lyon, France; Department of Paediatric Oncology, Hôpital Michalon, Grenoble; Department of Paediatric Oncology, Hôpital d'enfants, Nancy; Department of Paediatric Oncology, Centre hospitalo-universitaire, Besançon; Department of Paediatric Oncology, Hôpital Clocheville, Tours; Department of Paediatric Oncology, Hôpital Purpan, Toulouse; and the Department of Paediatric Oncology, Institut Curie, Paris, France

Address reprint requests to Odile Oberlin, MD, Department of Paediatric Oncology, Institut Gustave-Roussy, Rue Camille Desmoulins, 94805 Villejuif Cedex, France; e-mail: oberlin@igr.fr

PURPOSE: To improve the prognosis for patients with metastatic Ewing sarcoma/primitive neuroectodermal tumors (ES/PNET) using conventional chemotherapy and consolidation high-dose chemotherapy (HDCT) containing busulfan and melphalan.

PATIENTS AND METHODS: Ninety-seven unselected patients with newly diagnosed metastatic ES/PNET received induction chemotherapy that included five cycles of cyclophosphamide 150 mg/m2/d for 7 days, doxorubicin 35 mg/m2/d once, followed by two cycles of ifosfamide 1.8 g/m2/d for 5 days, and etoposide 100 mg/m2/d for 5 days. Patients in complete or very good partial remission received HDCT with busulfan total dose 600 mg/m2 and melphalan 140 mg/m2 followed by autologous blood stem cells. Local therapy (surgery and/or radiation therapy) was performed before or after HDCT.

RESULTS: Ninety-seven patients were enrolled from 1991 to 1999 (median age, 12.3 years; range, 0.2 to 25 years). Among them, 75 received HDCT. The 5-year event-free survival (EFS) rate for all 97 patients was 37% and the overall survival (OS) rate was 38%. The EFS after HDCT was 47%. The EFS for the 44 patients with lung-only metastases was 52%, whereas it was 36% for patients with bone metastases without bone marrow involvement. Among the 23 patients with bone marrow metastases, only one survived. The multivariate analysis for both EFS and for OS identified three independent prognostic factors: age, fever at diagnosis, and bone marrow involvement.

CONCLUSION: Compared with conventional chemotherapy, HDCT may yield benefits for patients with lung-only metastases or bone metastases. These results warrant confirmation in a randomized trial and provide part of the background data for the ongoing Euro-Ewing study.

Supported by Institut Gustave Roussy and by Société Française des Cancers de l'Enfant.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

The Use of Chemotherapy Medications, Gemcitabine (Gemzar) and Docetaxel (Taxotere) in the Treatment of Ewing's Sarcoma, Osteosarcoma, or Chondrosarcoma

Barry Sugarman — Sat, 09 Sep 2006 12:27:22 -0700

http://clinicaltrials.mayo.edu/clinicaltrialdetails.cfm?trial_id=100300

The Use of Chemotherapy Medications, Gemcitabine (Gemzar) and Docetaxel
(Taxotere) in the Treatment of Ewing's Sarcoma, Osteosarcoma, or
Chondrosarcoma

IRB Number : 1693-05

Trial Status : Open for Enrollment

Phase: II

Why is this study being done?
This study is being done to:
-See if the chemotherapy drugs gemcitabine (Gemzar) and docetaxel
(Taxotere), when given together, may help to fight cancer of the bone or
soft tissue. Each of these drugs is approved by the US Food and Drug
Administration (FDA) for the treatment of some kinds of cancer, such as
cancer of the pancreas and lung, but they are not approved for this type
of cancer, so in this study they are called investigational drugs.
-See what effects (good and bad) gemcitabine and docetaxel have on the
patient and the tumor.
-See how a patients body processes the gemcitabine and docetaxel.
-(When possible), to do genetic research studies on a sample of a
patients tumor tissue.

Who is Eligible to Participate in the Study?
-Patients diagnosed with Ewings sarcoma or Osteosarcoma, and have
received standard treatments for this type of cancer, but the tumor has
come back after treatment.
-Patients diagnosed with chondrosarcoma and the tumor cannot be
completely removed by surgery or has come back after surgery.
- Patients age 4 and older
-No prior treatment with gemcitabine or taxanes

*More specific, detailed eligibility and/ or exclusion criteria are
associated with this trial.

What is Involved With this Study?
-Medication given through a vein 2 times in a 3 week cycle, for up to 14
cycles
-Physical Exams
-Weekly Blood Tests
-X-rays, CT scans, MRI scans and/ or nuclear medicine scans including a
bone scan to measure patients tumor

How long will the Study run?
Patients will be in the study and receive treatment as long as the tumor
has stayed the same or has gotten smaller and patient has not had any
bad side effects, for up to 14 cycles (each cycle is 3 weeks). Treatment
will be stopped if patients tumor gets larger, if bad side effects, if
doctor thinks further treatment would not be in patients best interest,
if study closes, or if patient chooses to stop treatment.

Sponsor(s): MD Anderson Cancer Center

Study Activation: 12-19-2005

IRB Review and Approval Date: 9-8-2005

Study Type: Treatment

Projected Accrual: 10 patients

Costs of Study:There may be standard patient care costs related to
participating in a cancer research study.

Principal Investigator: Dr. Scott Okuno

Who can I Contact for Additional Information on this Trial?
If you are interested in participating in this study or would like
additional information, please contact Mayo Clinic's Cancer Center
Clinical Trials Referral Coordinator at (507) 538-7623.

What is/are the Locations of this Clinical Trial?
Rochester, MN

Ixabepilone to Treat Children and Young Adults with Solid Tumors

Barry Sugarman — Tue, 04 Jul 2006 16:27:25 -0700

http://www.clinicaltrials.gov/ct/gui/show/NCT00318526

Ixabepilone to Treat Children and Young Adults with Solid Tumors

This study is currently recruiting patients.
Verified by National Institutes of Health Clinical Center (CC) March 29, 2006

Sponsored by:	National Cancer Institute (NCI)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00318526

Purpose

Background:

-Ixabepilone is a member of a new class of anticancer drugs called epothilones, which interfere with the ability of cancer cells to divide. Ixabepilone kills cancer cells in the test tube and in animals.

-Epothilones are similar to a class of drugs called taxanes, which include Taxol® (Registered Trademark) (paclitaxel) and Taxotere® (Registered Trademark) (docetaxel). Epothilones can kill cancer cells that are resistant to Taxol® (Registered Trademark) in the laboratory.

-Ixabepilone has been tested in a small number of adults and children with cancers resistant to standard treatment.

Objectives:

-To measure the response of solid tumors to treatment with ixabepilone.

-To determine for how long ixabepilone can stop tumors from growing.

-To evaluate a new method of measuring tumors in the chest with a method that measures tumor volume.

-To further define the side effects of ixabepilone.

Eligibility:

-Patients with osteosarcoma, Ewing's sarcoma/peripheral neuroectodermal tumor, rhabdomyosarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor, neuroblastoma, or Wilms tumor.

-Patients must be 12 months or older when entering the study.

-Patients with sarcoma must have been no more than 35 years old at the time of diagnosis.

-Patients with Wilms tumor or neuroblastoma must have been no more than 21 years old at the time of diagnosis.

Design:

-Up to 20 patients with each type of tumor may be enrolled.

-Patients are given ixabepilone as a 1-hour infusion through a vein on days 1-5 of every 21-day cycle.

-Patients have a physical exam and urine test before each cycle, blood tests weekly, pregnancy test (for women who can bear children) every other cycle, and tests to evaluate the tumor (radiological, imaging, or others, depending on the tumor type) after the first cycle and then after every other cycle.

-Patients may continue treatment as long as their tumor responds to therapy and the side effects are not unacceptable.

Condition	Intervention	Phase
Refractory Solid Tumors	Drug: Ixabepilone	Phase II

MedlinePlus consumer health information

Study Type: Interventional
Study Design: Treatment, Safety/Efficacy

Official Title: Phase II Trial of Ixabepilone (BMS-247550), an Epothilone B Analog, in Children and Young Adults with Refractory Solid Tumors

Further study details as provided by National Institutes of Health Clinical Center (CC):

Expected Total Enrollment: 120

Study start: April 20, 2006

Background: Ixabepilone (BMS-247550) is a semi-synthetic analog of the natural product epothilone B. The epothilones are a novel class of non-taxane microtubule-stabilizing agents obtained from the fermentation of the cellulose degrading myxobacteria, Sorangium cellulosum. Ixabepilone is active against preclinical cancer models that are naturally insensitive to paclitaxel or have developed resistance to paclitaxel, both in-vitro and in-vivo. The National Cancer Institute (NCI) Pediatric Oncology Branch is conducting a phase I trial of Ixabepilone on a daily x 5 consecutive day schedule. The drug has been well tolerated in children at doses of up to 8 mg/m(2)/d.

Objectives: This Phase II trial is designed to establish the objective response rate (CR+PR) using RECIST criteria of Ixabepilone in solid tumors occurring in pediatric and young adult patients. Time to disease progression is a secondary trial endpoint. In addition, for patients with measurable chest disease, comparison of automated volumetric tumor measurement with standard RECIST and WHO methods is a secondary endpoint on this trial.

Eligibility: Patients will be accrued in one of six disease strata: osteosarcoma, Ewing's sarcoma/Peripheral neuroectodermal tumor (PNETs), rhabdomyosarcoma, synovial sarcoma and malignant peripheral nerve sheath tumor (MPNSTs), neuroblastoma, or Wilms tumor. Patients are eligible if they have measurable disease and have not previously received taxanes. Patients must be greater than or equal to 12 months old at trial entry. Patients with sarcoma must have been less than or equal to 35 years old at original diagnosis; patients with Wilms tumor or neuroblastoma must have been less than or equal to 21 years old at original diagnosis.

Design: Ixabepilone will be administered as a one-hour infusion on Days 1 to 5 every 21 days at a dose of 8 mg/m(2)/dose. The trial will use a two-stage design targeting a response rate of 30%. Up to 20 patients will be accrued to each tumor stratum.

Eligibility

Genders Eligible for Study: Both

Criteria

INCLUSION CRITERIA:

Important note: The eligibility criteria listed below are interpreted literally and cannot be waived (per COG policy posted 5/11/01). All clinical and laboratory data required for determining eligibility of a patient enrolled on this trial must be available in the patient's medical/research record which will serve as the source document for verification at the time of audit.

Age

-Patients must be greater than or equal to 12 months old at trial entry.

-Patients with neuroblastoma or Wilms tumor must have been less than 22 years of age when originally diagnosed with the malignancy to be treated on this protocol.

-All other patients must have been less than 36 years of age when originally diagnosed with the malignancy to be treated on this protocol.

Histologic Diagnosis

The target tumors are:

-Embryonal or alveolar rhabdomyosarcoma

-Osteosarcoma

-Ewing's sarcoma/Peripheral neuroectodermal tumor (PNET)

-Synovial sarcoma or malignant peripheral nerve sheath tumor (MPNST)

-Wilms tumor

-Neuroblastoma

Patients must have had histologic verification of the malignancy at original diagnosis or at recurrence.

All patients must have refractory or recurrent tumors with no known curative treatment options.

For patients with sarcoma and Wilms tumor:

Patients must have measurable disease. Measurable disease is defined as lesions that can be measured in at least one dimension by medical imaging techniques (CT or MRI scan). Ascites, pleural effusions, bone marrow disease, and lesions detectable only by bone scan will not be considered measurable disease.

For patients with neuroblastoma:

Patients with either clinically or radiographically measurable disease or evaluable disease by 123I-MIBG or bone scan are eligible.

-For evaluable tumor, (123)I-MIBG or bone scan must be positive at a minimum of one site. If the lesion was previously radiated, a biopsy must be done at least 6 weeks after radiation is complete and demonstrate viable neuroblastoma.

Performance Level

Patients must have an ECOG performance status of 0, 1 or 2, or Karnofsky greater than or equal to 50% (patients greater than 16 years of age) or Lansky greater than or equal to 50% (patients less than or equal to 16 years).

Life Expectancy

Patients must have a life expectancy of greater than or equal to 8 weeks.

Prior Therapy

Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

-Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study (4 weeks if prior nitrosourea).

-Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent.

-XRT: greater than or equal to 2 wks for local palliative XRT (small port); greater than or equal to 6 months must have elapsed if prior craniospinal XRT or if greater than or equal to 50% radiation of pelvis; greater than or equal to 6 wks must have elapsed if other substantial BM radiation.

-Stem Cell Transplant (SCT): No evidence of active graft vs. host disease. For allogeneic SCT, greater than or equal to 4 months must have elapsed; for autologous SCT greater than or equal to 2 months must have elapsed.

-Study specific limitations on prior therapy: Patients may not have received prior taxane (paclitaxel, docetaxel) therapy.

Concomitant Medications Restrictions

No other cancer chemotherapy or immunomodulating agents (including steroids) will be used. However, steroids may be used for the treatment and prevention of hypersensitivity reactions, if necessary.

Growth factor(s): Must not have received within 1 week of entry onto this study, with the exception of erythropoietin.

Study Specific: Patients may not be currently receiving strong inhibitors of CYP3A4, and may not have received these medications within 1 week of entry. These include:

-Antibiotics: clarithromycin, erythromycin, troleandomycin

-Antifungals: itraconazole, ketoconazole, fluconazole (doses greater than 3 mg/kg/day), voriconazole

-Antidepressants: nefazodone, fluovoxamine

-Calcium channel blockers: verapamil, diltiazem

-Antiemetics: Do not use aprepitant (Emend® (Registered Trademark)) as it is CYP3A4 substrate, moderate inhibitor and inducer.

-Miscellaneous: amiodarone,

-In addition, grapefruit juice should be avoided, as it inhibits CYP3A4.

-Patients must also avoid St. John's Wort, an inducer of CYP3A4.

-Patients may not be taking enzyme -inducing anticonvulsants, and may not have received these medications within 1 week of entry, as these patients may experience different drug disposition. These medications include:

-Carbamazepine (Tegretol)

-Felbamate (Felbtol)

-Phenobarbital

-Phenytoin (Dilantin)

-Primidone (Mysoline)

-Oxcarbazepine (Trileptal)

Organ Function Requirements

All patients must have:

Adequate Bone Marrow Function Defined As

-Peripheral absolute neutrophil count (ANC) greater than or equal to 1500/uL (off growth factors)

-Platelet count greater than or equal to 75,000/uL (transfusion independent)

-Hemoglobin greater than or equal to 10.0 gm/dL (may receive RBC transfusions)

Adequate Renal Function Defined As

Creatinine clearance or radioisotope GFR greater than or equal to 60mL/min/1.73m(2)

A serum/plasma creatinine calculation of GFR 60mL/min/1.73m(2) using the Schwartz formula

(Schwartz et al. J. Peds, 106:522, 1985)

Estimated Creatinine Clearance (in mL/min/1.73 m(2))

(k)(L)/Pcr

Where L &eq; child's length in cm

Pcr &eq; plasma (or serum) creatinine (in mg/dL)

K Values &eq;

0.33 low birth weight infant

0.45 term infant

0.55 child

0.55 adolescent female

0.70 adolescent male

**The conversion formula for serum/plasma creatinine when reported in

uMol/L units:

(k " ht)/(sCr in uMol/L " 88.4)

Adequate Liver Function Defined As

-Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN) for age, and

-SGPT (ALT) less than or equal to 2.5 x upper limit of normal (ULN) for age.

Nervous System Function Defined As

-Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled. Enzyme inducing anticonvulsant drugs are not allowed on this trial.

-CNS toxicity less than or equal to Grade 2.

-Existing sensory or motor neuropathy must be grade less than or equal to1.

EXCLUSION CRITERIA:

-Clinically significant unrelated systemic illness, such as serious infections, hepatic, renal or other organ dysfunction, which would, in the judgment of the treating physician, compromise the patient's ability to tolerate the investigational agent or is likely to interfere with the study procedures or results.

-Pregnant or breast-feeding females, because Ixabepilone may be harmful to the developing fetus or nursing child. Patients of child-bearing potential must use appropriate birth control measures.

-Patients with known severe prior hypersensitivity reaction to agents containing Cremophor EL.

-Patients with active brain metastases.

For patients with sarcoma and Wilms tumor:

Ascites, pleural effusions, bone marrow disease, and lesions detectable only by bone scan will not be considered measurable disease. Patients who have disease in these locations without radiographically measurable (CT, MRI) disease are excluded.

For patients with neuroblastoma:

Patients with elevated urinary catecholamines and/or bone marrow evidence of tumor, without measurable or evaluable disease clinically or by imaging modalities (CT, MRI, MIBG, or Bone Scan) are excluded.

Location and Contact Information

Please refer to this study by ClinicalTrials.gov identifier NCT00318526

Maryland
National Cancer Institute (NCI), 9000 Rockville Pike, Bethesda, Maryland, 20892, United States; Recruiting

Patient Recruitment and Public Liaison Office 1-800-411-1222 prpl@mail.cc.nih.gov
TTY 1-866-411-1010

More Information

Detailed Web Page

Publications

Jordan A, Hadfield JA, Lawrence NJ, McGown AT. Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle. Med Res Rev. 1998 Jul;18(4):259-96. Review.

Wilson L, Jordan MA. Microtubule dynamics: taking aim at a moving target. Chem Biol. 1995 Sep;2(9):569-73. Review.

Huizing MT, Misser VH, Pieters RC, ten Bokkel Huinink WW, Veenhof CH, Vermorken JB, Pinedo HM, Beijnen JH. Taxanes: a new class of antitumor agents. Cancer Invest. 1995;13(4):381-404. Review.

Study ID Numbers: 060146; 06-C-0146
Last Updated: June 3, 2006
Record first received: April 25, 2006
ClinicalTrials.gov Identifier: NCT00318526
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2006-07-03

Pharming Recieves Orphan Drug Designations For rhC1INH From US FDA

Barry Sugarman — Sun, 18 Jun 2006 00:35:34 -0700

http://www.pharming.com/index.php?act=show&pg=278

Pharming Recieves Orphan Drug Designations For rhC1INH From US FDA

Leiden, The Netherlands, June 14, 2006. Biotech company Pharming Group NV (“Pharming” or “the Company”) (Euronext: PHARM) announced today it has received orphan drug designations for recombinant human C1 inhibitor (rhC1INH) from the Food and Drug Administration (FDA). The Company has obtained designations on rhC1INH for two separate disease indications - the prevention and/or the treatment of Delayed Graft Function (DGF) after solid organ transplantation and the treatment of Capillary Leakage Syndrome (CLS).

Over 25,000 solid organs were transplanted in the US in 2005, including kidney, liver, lung and heart transplants. Delayed Graft Function is a common complication affecting all solid organs in the post-transplant period. DGF results in significant morbidity and mortality from early graft dysfunction and from decreased long-term graft survival. The condition also prolongs hospitalization and requires substitute therapies for these patients, such as dialysis or ventilatory support. DGF remains a critical unmet medical need despite improvements in immunosuppression, organ preservation, and surgical technique. C1 inhibitor has been shown in numerous models of organ transplantation to improve early graft function.

Over 100,000 patients in the US develop Capillary Leakage Syndrome annually as a complication of various disease states, including bone marrow/stem cell transplantation, IL-2 therapy, sepsis, and neonatal cardiac surgery. CLS is a severe life-threatening condition characterized by excessive fluid loss into the tissue space, which can result in hemodynamic instability, pulmonary edema, ascites, and death. Current therapies for patients with CLS are limited to supportive care and treatment of the underlying condition. Previous clinical work has demonstrated that C1 inhibitor may be an effective anti-inflammatory that can control the mechanisms contributing to CLS.

"Pharming’s rhC1INH product could provide new treatments for immune mediated diseases such as Delayed Graft Function in organ transplantation and Capillary Leakage Syndrome, conditions with a high burden and limited treatment options for patients,” said Dr. Francis Pinto, CEO of Pharming. “The Orphan Drug designations from the FDA further validate the potential of rhC1INH as an innovative therapy and are a significant achievement as we advance development of rhC1INH for these indications.”

The FDA Orphan Drug designation is reserved for promising new therapies being developed to treat diseases that affect fewer than 200,000 people in the United States. This designation provides an accelerated review process, tax advantages and a seven-year period of market exclusivity in the US upon product approval. Pharming also has an Orphan Drug designation on rhC1INH for the treatment of Hereditary Angioedema.

Background on Pharming Group NV
Pharming Group NV is developing innovative protein products for unmet needs. The Company’s products include potential treatments for genetic disorders, specialty products for surgical indications, intermediates for various applications and food products. Pharming has two products in late stage development - recombinant human C1 inhibitor for Hereditary Angioedema (Phase III) and recombinant human lactoferrin for use in functional foods. The advanced technologies of the Company include innovative platforms for the production of protein therapeutics, as well as technology and processes for the purification and formulation of these products. Additional information is available on the Pharming website: http://www.pharming.com.

This press release contains forward looking statements that involve known and unknown risks, uncertainties and other factors, which may cause the actual results, performance or achievements of the Company to be materially different from the results, performance or achievements expressed or implied by these forward looking statements. The press release also appears in Dutch. In the event of any inconsistency, the English version will prevail over the Dutch version.

Contact:

Carina Hamaker, Investor Voice, T: +31 (0)6 537 49959
Sarah MacLeod, Financial Dynamics, T: +44 (0)20 7269 7148
Samir Singh, Pharming Group NV, T: +31 (0)71 524 7429

Neurosurgical Use of Interstitial Laser Therapy (ILT)

Barry Sugarman — Tue, 18 Apr 2006 19:45:42 -0700

http://www.clinicaltrials.gov/ct/show/NCT00207350

Neurosurgical Use of Interstitial Laser Therapy (ILT)

This study is currently recruiting patients.
Verified by Brigham and Women's Hospital September 2005

Sponsored by:	Brigham and Women's Hospital
Information provided by:	Brigham and Women's Hospital
ClinicalTrials.gov Identifier:	NCT00207350

Purpose

Our specific aims are to test the following hypotheses: Hypothesis 1: A tumor can be completely ablated by ILT with MRI-guidance; Hypothesis 2: The MRI-based 3D temperature map of tissue during ILT is predictive of destruction; Hypothesis 3: The 3D “thermal dose” map that is based on the tissue’s temperature over time is more predictive of tissue destruction than the temperature map.

Condition	Intervention
Brain Tumor	Device: Interstitial Laser Therapy

MedlinePlus related topics: Brain Cancer

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study

Further study details as provided by Brigham and Women's Hospital:

Primary Outcomes: A tumor can be completely ablated by ILT with MRI-guidance
Secondary Outcomes: Patients undergoing ILT will be assessed pre- and post-operatively based on a neurological exam by a physician and patient self-assessment using the Glioma Outcomes Questionnaire.
Expected Total Enrollment: 24

Study start: January 2002
Last follow-up: December 2004

The goal is to evaluate the use of minimally invasive interstitial laser therapy (ILT) in the brain. Our group is in a unique position to offer image-guided ILT because of our expertise and resources here at Brigham & Women's Hospital in the Departments of Neurosurgery and Radiology. The therapy will be monitored and controlled by the use of magnetic resonance imaging (MRI). ILT is a minimally invasive procedure in which the targeted tissue is thermally destroyed in situ in a controlled fashion. The intra-operative MRI provides a way to "see" the treatment. It can be used to treat disease by guiding surgery by providing images of tissue changes during therapy.

In spite of its appeal as a minimally invasive technique, MRI-guided ILT is not commonly practiced in the United States. One reason is that proper clinical implementation of ILT requires an operating room (OR) setting and an MRI scanner - a very rare combination. Our MRI-OR suite includes a sterile procedure room with a 0.5 Tesla vertically "open" magnet. In the past, we have performed MRI-guided ILT procedures in 9 patients. While few in number, this is the most extensive U.S. experience in ILT in the brain.

We have recently created a new image networking and display package for the visualization of 3D information during laser therapy. This provides a view of multiple image planes taken through the tissue volume around the fiber tip.

Each patient will undergo ILT. The procedure will be performed under anesthesia as per standard procedures. The surgical placement of the laser fiber is a procedure identical to the well-developed and practiced technique of brain biopsy. A hole approximately 1 cm in diameter will be drilled in the skull through which the laser fiber will be placed under image guidance to confirm the actual progress during the advance of the fiber. We will deliver energy at a rate and distribution of 1-12 watts/cm for exposures less than 20 minutes. After the laser has been turned off, and the tissue cooled, MRI will show the region of ablation. As needed, the laser fiber will be moved/re-located to assure that the total target has been ablated. After the treatment is complete, the fiber is withdrawn, final images are acquired and the surgical site is closed and dressed. On the day after the procedure, the patient will undergo a 24 hr follow-up MRI exam. There will be post-operative care as with any neurosurgical patient.

The following continuous variables will be measured in this study.

the pre-operative tumor volume (VO) in cc
the post-operative ablated volume (V1) in cc
the intra-operative critical temperature volume (VT) in cc
the intra-operative critical dose volume (VD) in cc.

The following statistical hypothesis tests will be conducted.

Statistical Hypothesis 1. A tumor can be completely ablated by ILT with MRI-guidance.

We propose that the difference between the mean the pre-op tumor volumes and the post-op ablated volumes (VO and V1, respectively) is zero. Residual tumor is defined as (V0-V1). This will be determined by calculating the mean of the values of the proportion of residual tumor, defined as (V0-V1)/ V0.Use of the proportion normalizes the data for different sized tumors.

Statistical Hypothesis 2. The MRI-based 3-D temperature map of the tissue during ILT is predictive of destruction. We propose that the difference between the mean post-op ablated volumes and the intra-operative critical temperature volumes (VT and V1, respectively) is zero. This will be determined by calculating the mean of the values of the proportion of the difference between them, defined as (VT-V1)/VT.

Statistical Hypothesis 3. The thermal dose map is predictive of tissue destruction.

We propose that the difference between the mean post-op ablated volumes and the intra-operative critical dose volumes (VD and V1, respectively) is zero. This will be determined by calculating the mean of the values of the proportion of the difference between them, defined as (VD-V1 /VD).

Also, data will be collected through Neurological Examinations and GOC Questionnaire.

Eligibility

Ages Eligible for Study: 18 Years and above, Genders Eligible for Study: Both

Criteria

Inclusion Criteria:

Male or female Age 18+ Surgically difficult to access tumors including intracerebral metastases and vascular malformations

Exclusion Criteria:

Patients unwilling or unable to give written consent Patients at risk for cardiac ischemia Patients who cannot physically fit in the MRI scanner in the MRI OR Patients with contra-indications to MRI imaging such as pacemakers, non-compatible aneurysm clips, shrapnel, and other internal ferromagnetic objects Patients with coagulopathies, severe medical problems, cardiac arrythmias or abnormal BUN -

Location and Contact Information

Please refer to this study by ClinicalTrials.gov identifier NCT00207350

Joanne E O'Hara, M.A. 617-732-6992 johara1@partners.org
Donna Dello Iacono, RN, MS 617-732-6826 ddelloiacono@partners.org

Massachusetts
Brigham & Women's Hospital, Boston, Massachusetts, 02115, United States; Recruiting

Peter M Black, MD, PhD, Principal Investigator

Study chairs or principal investigators

Peter M Black, MD, PhD, Principal Investigator, Brigham and Women's Hospital

More Information

Website for Image Guided Therapy Program at Brigham & Women's Hospital

Publications

Schulze PC, Vitzthum HE, Goldammer A, Schneider JP, Schober R. Laser-induced thermotherapy of neoplastic lesions in the brain--underlying tissue alterations, MRI-monitoring and clinical applicability. Acta Neurochir (Wien). 2004 Aug;146(8):803-12. Epub 2004 Jun 7. Review.

Peller M, Muacevic A, Reinl H, Sroka R, Abdel-Rahman S, Issels R, Reiser MF. [MRI-assisted thermometry for regional hyperthermia and interstitial laser thermotherapy] Radiologe. 2004 Apr;44(4):310-9. German.

McNichols RJ, Gowda A, Kangasniemi M, Bankson JA, Price RE, Hazle JD. MR thermometry-based feedback control of laser interstitial thermal therapy at 980 nm. Lasers Surg Med. 2004;34(1):48-55.

Leonardi MA, Lumenta CB. Stereotactic guided laser-induced interstitial thermotherapy (SLITT) in gliomas with intraoperative morphologic monitoring in an open MR: clinical expierence. Minim Invasive Neurosurg. 2002 Dec;45(4):201-7.

Straube T, Kahn T. Thermal therapies in interventional MR imaging. Laser. Neuroimaging Clin N Am. 2001 Nov;11(4):749-57. Review.

Muacevic A, Peller M, Sroka R, Kalusche B, Pongratz T, Kreth FW, Steiger HJ, Reiser M, Reulen HJ. [Brain protective interstitial laser thermotherapy. Therapy of brain tumors without secondary damage] MMW Fortschr Med. 2001 May 28;143 Suppl 2:87-8. German.

Study ID Numbers: 2001-P-001794
Last Updated: December 8, 2005
Record first received: September 12, 2005
ClinicalTrials.gov Identifier: NCT00207350
Health Authority: United States: Institutional Review Board
ClinicalTrials.gov processed this record on 2006-04-18

High histologic and overall response to dose intensification of ifosfamide, carboplatin, and etoposide with cyclophosphamide, doxorubicin, and vincristine in patients with high-risk ewing sarcoma family tumors

Barry Sugarman — Sat, 01 Apr 2006 10:46:08 -0800

http://www3.interscience.wiley.com/cgi-bin/abstract/112476870

High histologic and overall response to dose intensification of ifosfamide, carboplatin, and etoposide with cyclophosphamide, doxorubicin, and vincristine in patients with high-risk ewing sarcoma family tumors

The Bambino Gesù Children's Hospital experience
Giuseppe Maria Milano, M.D. 1 *, Raffaele Cozza, M.D. 1, Ilaria Ilari, M.D. 1, Luigi De Sio, M.D. 1, Renata Boldrini, M.D. 2, Alessandro Jenkner, M.D. 1, Maretta De Ioris, M.D. 1, Alessandro Inserra, M.D. 3, Carlo Dominici, M.D. 1 4, Alberto Donfrancesco, M.D. 1
1Division of Pediatric Oncology, Ospedale Pediatrico Bambino Gesù-IRCCS, Rome, Italy
2Division of Pathology, Ospedale Pediatrico Bambino Gesù-IRCCS, Rome, Italy
3Division of Pediatric Surgery, Ospedale Pediatrico Bambino Gesù-IRCCS, Rome, Italy
4Department of Pediatrics, La Sapienza University, Rome, Italy
email: Giuseppe Maria Milano (milano_gm@hotmail.com)

*Correspondence to Giuseppe Maria Milano, Dipartimento di Oncoematologia Pediatrica e Servizio Immunotrasfusionale, UO di Oncologia, Ospedale Pediatrico Bambino Gesù-IRCCS, Piazza Sant'Onofrio 4, Rome, 00165, Italy
Fax: (011) 396 68592242

Keywords
Ewing sarcoma family tumors • chemotherapy • dose intensification • histologic response • tumor necrosis • survival

Abstract

BACKGROUND
Ewing sarcoma (ES) and extraosseous ES/primitive neuroectodermal tumors (PNET) share histopathologic features of the ES family of tumors (ESFT). The authors report on their results from a regimen of ifosfamide, carboplatin, and etoposide (ICE) with cyclophosphamide, doxorubicin, and vincristine (CAV) dose intensification in patients with high-risk ESFT.

METHODS
Since 1990, patients with ESFT and with 1 or more of the following risk factors were reviewed: tumor volume > 200 mL, tumor site with a poor prognosis, and pulmonary and/or bone marrow metastases.

RESULTS
Thirty-six patients with ESFT who were involved in the study were divided into 2 arms of 18 patients each. One group received treatment with various regimens, and the other group received treatment with ICE plus CAV. The disease was brought under control more rapidly in the latter patients, for whom surgery was more easily feasible, and up to 90% of patients achieved a major response, with an estimated 3-year overall survival rate of 67% ± 12%.

CONCLUSIONS
The current results showed that ICE plus CAV was tolerated well and was effective in the studied subset of tumors, indicating that dose intensification correlates with better disease control, a high percentage of necrosis, and conservative surgery in patients with high-risk ESFT. Cancer 2006. © 2006 American Cancer Society.

New Federal Health Initiative to Improve Cancer Therapy Patients will Benefit from Rapid Development and Delivery of New Cancer Treatments

Barry Sugarman — Tue, 21 Feb 2006 22:51:23 -0800

http://www.fda.gov/bbs/topics/news/2006/NEW01316.html

Press Release

FOR IMMEDIATE RELEASE
Tuesday, February 14, 2006

FDA Press Office
301-827-6242
NCI Press Office
(301) 496-6641
CMS Press Office
(202) 690-6145

New Federal Health Initiative to Improve Cancer Therapy
Patients will Benefit from Rapid Development and Delivery of New Cancer Treatments

The Food and Drug Administration (FDA), the National Cancer Institute (NCI), part of the National Institutes of Health, and the Centers for Medicare & Medicaid Services (CMS) today announced the Oncology Biomarker Qualification Initiative (OBQI) -- an agreement to collaborate on improving the development of cancer therapies and the outcomes for cancer patients through biomarker development and evaluation.

Biomarkers are biologic indicators of disease or therapeutic effects, which can be measured through dynamic imaging tests, as well as tests on blood, tissue and other biologic samples. This initiative is the first time these three Department of Health and Human Services (HHS) agencies have focused together on biomarkers as a way of speeding the development and evaluation of cancer therapies.

"We are excited about this effort to speed the development and delivery of new cancer treatments for patients," said Secretary of Health and Human Services Mike Leavitt. "By bringing together the scientific, regulatory and delivery expertise of these three agencies, we can bring targeted, more personalized cancer diagnostics, treatments and preventions to patients more rapidly."

The collaboration will develop scientific understanding of how biomarkers can be used to assess the impact of therapies and better match therapies to patients. For instance, OBQI will address questions such as how particular biomarkers can be used to:

Assess after one or two treatments if a patient';s tumor is responding to treatment
Determine more definitively if a tumor is dying, even if it is not shrinking
Identify which cancer patients are at high risk of their tumor coming back after therapy
Determine if a patient';s tumor is likely to respond at all to a specific treatment
Efficiently evaluate whether an investigational therapy is effective for tumor treatment.

The goal of OBQI is to validate particular biomarkers so that they can be used to evaluate new, promising technologies in a manner that will shorten clinical trials, reduce the time and resources spent during the drug development process, improve the linkage between drug approval and drug coverage, and increase the safety and appropriateness of drug choices for cancer patients.

"Almost four years ago, NIH set out to create a "roadmap" for 21st century medical research. Programs like OBQI will be central to that vision, not only because they will lead to vital discoveries about the biology of disease, but because they will be models for scientific collaboration," said NIH Director Elias A. Zerhouni, M.D.

"An enhanced understanding of clinical biomarkers will help make the development of diagnostics and treatments more targeted, one of our most pressing goals under the Critical Path Initiative, FDA';s program to modernize the medical product development process," said FDA Acting Commissioner of Food and Drugs Andrew C. von Eschenbach, M.D. "We believe partnerships that help us standardize the use of new technologies are essential to refining the drug development process, so we can bring personalized medicines to patients more quickly and ultimately improve outcomes."

Under the OBQI, biomarker research will be focused in four key areas: standardizing and evaluating imaging technologies to see in more detail how treatments are working, developing scientific bases for diagnostic assays to enable personalized treatments, instituting new trial designs to utilize biomarkers, and pooling data to ensure that key lessons are shared from one trial to another. By working with academic and industry scientists, as well as professional organizations, the OBQI teams can foster the development of key information on biomarkers through clinical trials.

"By identifying biomarkers for specific cancers and clinically evaluating them, researchers will have an evidence base for their use in targeted drug development and to determine which therapies are likely to work for patients before treatment selection," said NCI Deputy Director Anna D. Barker, Ph.D. "Rather than waiting weeks to months to determine if a specific drug works for a patient, biomarkers could be used to monitor real-time treatment responses."

The first OBQI project to be implemented will serve to validate and standardize the use of Fluorodeoxyglucose - Positron Emission Tomography (FDG-PET) scanning. PET scans are used to characterize biochemical changes in a cancer. Under the collaboration, researchers will use FDG-PET imaging technology in trials of patients being treated for non-Hodgkin';s lymphoma, to determine if FDG-PET is a predictor of tumor response. Data resulting from this type of evidence-based study will help both FDA and CMS work with drug developers based on a common understanding of the roles of these types of assessments.

"There are many steps between a novel scientific idea with tremendous promise and a new drug reliably benefiting patients," said CMS Administrator Mark B. McClellan, M.D., Ph.D. "This collaboration will produce evidence that will help people with Medicare and Medicaid get better care more quickly, as a result of better-targeted treatment decisions for cancer patients."

Over the next several months, the OBQI team will design a number of initiatives to identify and clinically qualify other cancer biomarkers. The new initiatives will bring together scientists from many sources and address agency priorities identified through FDA';s Critical Path and NIH';s Roadmap Initiatives. The OBQI also represents the work of the NCI-FDA Interagency Oncology Task Force (IOTF). The IOTF is a collaboration between NCI and FDA to enhance the efficiency of clinical research and the scientific evaluation of new cancer treatments. The two agencies, along with CMS, share knowledge and resources to facilitate the development of new cancer drugs and diagnostics and speed their delivery to patients as safely and as cost-effectively as possible.

FDA Critical Path

Critical Path is the FDA';s premier initiative to identify and prioritize the most pressing medical product development problems and the greatest opportunities for rapid improvement in public health benefits. Its primary purpose is to ensure that basic scientific discoveries translate more rapidly into new and better medical treatments by creating new tools to find answers about how the safety and effectiveness of new medical products can be demonstrated in faster timeframes with more certainty and at lower costs.

The NIH Roadmap

The NIH Roadmap is a series of new initiatives designed to pursue major opportunities and gaps in biomedical research that no single NIH institute could tackle alone, but which the agency as a whole can address to make the biggest impact possible on the progress of medical research, and to catalyze changes that will serve to transform new scientific knowledge into tangible benefits for public health. Additional information about the NIH Roadmap can be found at its Web site, www.nihroadmap.nih.gov.

For information about the Food and Drug Administration, please visit http://www.fda.gov.
For additional information about the National Cancer Institute, please visit http://www.cancer.gov.
For information about the Centers for Medicare & Medicaid Services, please visit http://cms.hhs.gov.

FDA/NCI/CMS Memorandum of Understanding

###

Clinical Trial: Summary: Study of Gamma Knife Radio Surgery and Temozolomide for Patients with 1- 4 Unresected Brain Metastases

Barry Sugarman — Tue, 21 Feb 2006 17:12:10 -0800

Clinical Trial: Summary: Study of Gamma Knife Radio Surgery and Temozolomide for Patients with 1- 4 Unresected Brain Metastases

http://www.centerwatch.com/patient/studies/stu87321.html

Summary: Study of Gamma Knife Radio Surgery and Temozolomide for Patients with 1- 4 Unresected Brain Metastases
The purpose of this study is to determine if Gamma Knife radiosurgery with Temodar improves the overall survival time of patients with one to four brain metastases (cancer to the brain). All patients will receive stereotactic radiosurgery (Gamma Knife), done on a single day, outpatient procedure and chemotherapy with temodar may be given up to 24 months, depending on your tumor response.

Patient Inclusion Criteria

Confirmed diagnosis of cancer with 1-4 brain metastases.
No previous cranial radiation.
No chemotherapy within one month prior to treatment.
No prior surgery for brain metastases.
No allergy to MRI contrast dye.
Age > 18.
Patient Exclusion Criteria

Diagnosis of lymphoma, small cell lung cancer and germ cell tumor.
Systemic therapy within 1 month prior to treatment.
Major medical illnesses or psychiatric impairments, which in the investigator's opinion will prevent administration of completion of the protocol therapy and/or interfere with follow-up.
All patients who have undergone a complete resection of all known brain metastases.

Contact:

Laszlo Mechtler, MD
Roswell Park Cancer Institute
Elm & Carlton Streets
Buffalo, NY 14263
Telephone: 716-845-3154
Email: Laszlo.mechtler@roswellpark.org

This site is run by CenterWatch, a publishing company that focuses on the clinical trials industry. The information provided in this service is designed to help patients find clinical trials that may be of interest to them, and to help patients contact the centers conducting the research. CenterWatch is neither promoting this research nor involved in conducting any of these trials.

Trial listings updated: February 17, 2006 at 3:52:01 PM

Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Refractory, Recurrent, or Advanced CNS or Leptomeningeal Cancer

Barry Sugarman — Tue, 21 Feb 2006 16:03:19 -0800

Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Refractory, Recurrent, or Advanced CNS or Leptomeningeal Cancer
http://www.clinicaltrials.gov/ct/show/NCT00089245?order=100

This study is currently recruiting patients.
Verified by National Cancer Institute (NCI) August 2004
Sponsors and Collaborators: Memorial Sloan-Kettering Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00089245

Purpose

RATIONALE: Radiolabeled monoclonal antibodies can locate tumor cells and deliver tumor-killing substances, such as radioactive iodine, to them without harming normal cells.

PURPOSE: This phase I trial is studying the side effects and best dose of radiolabeled monoclonal antibody therapy in treating patients with refractory, recurrent, or advanced CNS or leptomeningeal cancer.

Condition                                                                             Intervention                                                    Phase
Adult Brain Tumor                                                                 Drug: iodine I 131 monoclonal antibody 8H9     Phase I
Adult Medulloblastoma                                                          Procedure: antibody therapy
Adult Rhabdomyosarcoma                                                   Procedure: biological response modifier therapy
Adult Soft Tissue Sarcoma                                                     Procedure: isotope therapy
Childhood Medulloblastoma                                                   Procedure: monoclonal antibody therapy
Childhood Rhabdoid Tumor of the Central Nervous System    Procedure: radiation therapy
Childhood Rhabdomyosarcoma                                              Procedure: radioimmunotherapy
Childhood Soft Tissue Sarcoma
Desmoplastic Small Round-Cell Tumor
Disseminated Neuroblastoma
Leptomeningeal Metastases
Metastatic Childhood Soft Tissue Sarcoma
Metastatic Osteosarcoma
Metastatic Tumors of the Ewing's Family
Neuroblastoma
Osteosarcoma
Previously Treated Childhood Rhabdomyosarcoma
Tumors of the Ewing's Family

MedlinePlus related topics: Bone Cancer; Brain Cancer; Cancer; Cancer Alternative Therapies; Neuroblastoma;   Neurologic Diseases; Soft Tissue Sarcoma
Genetics Home Reference related topics: Cancer; Neurologic Diseases

Study Type: Interventional
Study Design: Treatment

Official Title: Phase I Study of Intrathecal Iodine I 131 Monoclonal Antibody 8H9 in Patients With Refractory, Recurrent, or Advanced CNS or Leptomeningeal Cancer

Further study details as provided by National Cancer Institute (NCI):

OBJECTIVES:

   * Determine the maximum tolerated dose of intrathecal iodine I 131 monoclonal antibody 8H9 in patients with refractory,
        recurrent, or advanced CNS or leptomeningeal cancer.
   * Determine the clinical toxic effects of this drug in these patients.
   * Determine the pharmacokinetics and dosimetry of this drug in these patients.
   * Correlate tumor response by MRI with CSF reverse-transcription polymerase chain reaction in patients treated with
this drug.

OUTLINE: This is a dose-escalation study.

Patients receive iodine I 131 monoclonal antibody 8H9 (^131I MOAB 8H9) intrathecally on day 1. Treatment repeats every 4 weeks for up to 2 courses (total of 2 injections) in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of ^131I MOAB 8H9 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study within 2-3 years.

Eligibility
Genders Eligible for Study: Both
Criteria

DISEASE CHARACTERISTICS:

   * Histologically confirmed CNS or leptomeningeal cancer, meeting 1 of the following criteria:
   * Refractory to conventional therapy OR for which no conventional therapy exists
   * Less than 10% chance of cure with conventional therapy
   * Recurrent brain tumor or other solid tumor with a predilection for leptomeningeal dissemination, including, but not
limited to, the following:
   * Medulloblastoma
   * Ewing's sarcoma/primitive neuroectodermal tumor
   * Rhabdoid tumor
   * Neuroblastoma
   * Osteosarcoma
   * Desmoplastic small rounded-cell tumor
   * Rhabdomyosarcoma
   * 8H9 reactivity confirmed by immunohistochemical staining
   * No rapidly progressing or deteriorating neurologic examination
   * Stable neurological deficits as a result of brain tumor allowed
   * No obstructive or symptomatic communicating hydrocephalus

PATIENT CHARACTERISTICS:

Age
    * Any age

Performance status
    * Not specified

Life expectancy
    * Not specified

Hematopoietic
    * Absolute neutrophil count > 1,000/mm^3
    * Platelet count > 50,000/mm^3

Hepatic
    * No hepatic toxicity ≥ grade 2

Renal
    * No renal toxicity ≥ grade 2

Cardiovascular
    * No cardiac toxicity ≥ grade 2

Pulmonary
    * No pulmonary toxicity ≥ grade 2

Other
    * Not pregnant or nursing
    * Negative pregnancy test
    * Concurrent active malignancy outside the CNS allowed
    * No uncontrolled life-threatening infection
    * No gastrointestinal system toxicity ≥ grade 2
    * No other severe major organ toxicity
    * Hearing loss ≤ grade 3

PRIOR CONCURRENT THERAPY:

Biologic therapy
    * Not specified

Chemotherapy
    * At least 3 weeks since prior systemic chemotherapy

Endocrine therapy
    * Prior corticosteroids allowed

Radiotherapy
    * At least 3 weeks since prior cranial or spinal radiotherapy

Surgery
    * Not specified

Location and Contact Information
Please refer to this study by ClinicalTrials.gov identifier NCT00089245

New York
      Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, United States; Recruiting
      Clinical Trials Office for Memorial Sloan-Kettering Cancer Cen 646-227-2149

Study chairs or principal investigators
      Kim Kramer, MD, Study Chair, Memorial Sloan-Kettering Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database
Study ID Numbers: CDR0000378183; MSKCC-03133
Last Updated: February 7, 2006
Record first received: August 4, 2004
ClinicalTrials.gov Identifier: NCT00089245
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2006-02-21

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