This Month
| June 2008 |
| Sun |
Mon |
Tue |
Wed |
Thu |
Fri |
Sat |
|
1
|
2
|
3
|
4
|
5
|
6
|
7
|
|
8
|
9
|
10
|
11
|
12
|
13
|
14
|
|
15
|
16
|
17
|
18
|
19
|
20
|
21
|
|
22
|
23
|
24
|
25
|
26
|
27
|
28
|
|
29
|
30
|
|
Tuesday, June 3
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)
by
Barry Sugarman
on Tue 03 Jun 2008 11:25 PM PDT
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
by
Barry Sugarman
on Tue 03 Jun 2008 11:15 PM PDT
June 02, 2008 04:02 PM Eastern Daylight Time New Pfizer Data Presented on CP-751,871 acrossNon-Small Cell Lung
Cancer and Ewing’s Sarcoma ADVIGO CP-751,871 Global Phase III Clinical Trial Program
Initiated (ADVancing IGF-1R in Oncology)
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 44th
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.
Pfizer Inc
Media:
Vanessa Aristide, 917-697-0481 or
212-733-3784
or
Investors:
Jennifer Davis, 212-733-0717
Monday, June 2
More Frequent Chemotherapy Improves Outcome for Ewing’s Sarcoma Patients, Results of Children's Oncology Group Study Protocol No. AEWS0031
by
Barry Sugarman
on Mon 02 Jun 2008 09:55 PM PDT
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.
Monday, May 12
ZIOPHARM Presents Promising Early Data from Phase Ib Study of Indibulin at 6th International Symposium on Targeted Anticancer Therapies
by
Barry Sugarman
on Mon 12 May 2008 04:30 PM PDT
ZIOPHARM Presents Promising Early Data from Phase Ib Study ofIndibulin at 6th International Symposium on Targeted AnticancerTherapiesResults Shows Indibulin Is Well Tolerated and Active Among Eight
Evaluable Patientshttp://ir.ziopharm.com/releasedetail.cfm?ReleaseID=300540BETHESDA,
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
Tuesday, April 15
Amgen Presents Preclinical and Clinical Data from Oncology Programs Early Data Presented from Investigational Molecules that Target Apoptosis and Growth Regulation Pathways
by
Barry Sugarman
on Tue 15 Apr 2008 11:09 AM PDT
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
Sunday, April 13
In Lab Study, Researchers Find Molecule That Disrupts Ewing’s Sarcoma Oncogene
by
Barry Sugarman
on Sun 13 Apr 2008 12:58 AM PDT
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.
### |
Monday, March 17
Pharmamar Initiates A Phase II Study Of Yondelis® In Children With Recurrent Soft Tissue Sarcomas
by
Barry Sugarman
on Mon 17 Mar 2008 05:10 PM PDT
NEWS RELEASE
PHARMAMAR INITIATES A PHASE II STUDY OF YONDELIS®IN CHILDREN WITH RECURRENT SOFT TISSUE SARCOMAShttp://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. ::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::: For more information: www.pharmamar.com
Wednesday, March 5
Phase I/II Studies of IMC-A12 in Pediatric Cancer Patients Comence Enrollment
by
Barry Sugarman
on Wed 05 Mar 2008 11:12 AM PST
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
Sunday, February 10
Myeloablative therapy with autologous stem cell rescue for patients with Ewing sarcoma
by
Barry Sugarman
on Sun 10 Feb 2008 10:35 PM PST
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
Sunday, October 28
Early Stage Drug Shows Promise Against Cancer Cells from Young Patients
by
Barry Sugarman
on Sun 28 Oct 2007 08:35 PM PDT
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)
Tuesday, October 23
Roche Announces Positive Results in Solid Tumors Using Human Monoclonal Antibody against IGF-1R (R1507)
by
Barry Sugarman
on Tue 23 Oct 2007 08:47 PM PDT
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
Wednesday, June 27
Oncolytics Biotech Inc. Commences Patient Enrollment in U.S. Phase II Sarcoma Clinical Trial
by
Barry Sugarman
on Wed 27 Jun 2007 11:52 PM PDT
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
Tuesday, June 5
Hyperthermia Plus Chemotherapy Nearly Doubles Disease-Free Survival Compared to Chemotherapy Alone for Sarcoma Cancer Patients
by
Barry Sugarman
on Tue 05 Jun 2007 10:43 PM PDT
Hyperthermia Plus Chemotherapy Nearly Doubles Disease-Free Survival
Compared to Chemotherapy Alone for Sarcoma Cancer Patients
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.
Saturday, November 18
First report that apoptotic and anti-angiogenic therapies work better together than alone
by
Barry Sugarman
on Sat 18 Nov 2006 11:06 AM PST
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.
###
Monday, September 25
External Beam Radiation With Intratumoral Injection Of Dendritic Cells As Neo-Adjuvant Treatment for Sarcoma
by
Barry Sugarman
on Mon 25 Sep 2006 08:40 AM PDT
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 tha |
