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 Experimental therapy consists of leukapheresis which is the separation and removal of leukocytes from withdrawn blood, frozen for later use.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

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.

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