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by Tom Swartz This issue's Clinical Trial News column is divided into two sections. The first section describes various studies that include liposarcoma patients. This section augments the article Liposarcoma by Drs. Gebhardt and Buecker. The second section is an update on immunotherapy-related (vaccine-based and monoclonal antibody-based) clinical trials that initially appeared in conjunction with the article on Immunotherapy by Dr. Mary Louise Keohan in the April issue of ESUN. We also call your attention to the fact that there are several articles related to clinical trials in the Drug News column of this issue of ESUN.
Clinical Trials that Include Liposarcoma Patients This Phase III trial is currently recruiting patients. The purpose of this trial is to compare the effectiveness of surgery with or without radiation therapy in treating patients who have primary soft tissue sarcoma, including liposarcoma, of the retroperitoneum or pelvis. Patients are stratified according to tumor grade (low [G1] vs. intermediate [G2] vs. high [G3/4]), tumor size (< 15 cm vs. ≥ 15 cm), and tumor histology (liposarcoma vs. non-liposarcoma). Patients are randomized to 1 of 2 treatment arms.
In both arms, treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed at 28 days, 4 months, every 6 months for 5 years, and then annually for 5 years. A total of 370 patients (185 per treatment arm) will be accrued for this study within 4.5 years. Patients 18 years and older are eligible. This study is being conducted at the University of Texas - MD Anderson Cancer Center, Houston, Texas.
Vaccine Therapy and Sargramostim in Treating Patients With Sarcoma or Brain Tumor This Phase I trial is currently recruiting patients. The purpose of this trial is to study the effectiveness of combining vaccine therapy with sargramostim in treating patients who have advanced sarcoma, including liposarcoma, or brain tumor. Patients receive telomerase: 540-548 peptide vaccine subcutaneously (SC) on day 3 and sargramostim (GM-CSF) SC on days 1-4 of weeks 1, 3, 5, 7, 9, 11, 15, 19, and 23. A total of 35 patients (20 adult and 15 pediatric) will be accrued for this study. Patients 2 years of age and older are eligible. This study is being conducted at the Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston, Massachusetts.
Soblidotin in Treating Patients With Advanced or Metastatic Soft Tissue Sarcoma This Phase II trial is currently recruiting patients. The purpose of this trial is to study the effectiveness of soblidotin in treating patients who have advanced or metastatic soft tissue sarcoma, including liposarcoma. Patients receive soblidotin IV over 1 hour on days 1 and 8. Treatment repeats every 3 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. A total of 27 patients will be accrued for this study. Patients 15 years of age and above are eligible. This study is being conducted at centers in Alabama, Indiana, New York, Texas and Puerto Rico.
This Phase III trial is currently recruiting patients. The purpose of this trial is to compare the effectiveness of doxorubicin with or without ifosfamide in treating patients who have locally advanced or metastatic soft tissue sarcoma, including liposarcoma. Patients are stratified according to WHO performance status (0 vs. 1), age group (less than 50 years of age vs. 50 years of age and over), presence of liver metastases (yes vs. no), histological grade (2 vs. 3), and participating center. Patients are randomized to 1 of 2 treatment arms.
In both arms, treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 8 weeks until disease progression and then every 12 weeks thereafter. A total of 450 patients will be accrued for this study within 4 years. Patients 18 to 60 years of age are eligible. This study is being conducted at centers in Belgium and Slovakia.
Exatecan Mesylate in Treating Patients With Advanced Soft Tissue Sarcoma This Phase II trial is currently recruiting patients. The purpose of this trial is to study the effectiveness of exatecan mesylate in treating patients who have advanced soft tissue sarcoma, including liposarcoma. Patients are stratified according to histological diagnosis (leiomyosarcoma vs. other histologies). Patients receive exatecan mesylate IV over 30 minutes daily on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. A total of 32-50 patients (16-25 per stratum) will be accrued for this study. Patients 15 to 75 years of age are eligible. This study is being conducted at centers in Belgium, Denmark, Germany, and Slovakia.
This Phase I trial is currently recruiting patients. The purpose of this trial is to study the effectiveness of combining liposomal doxorubicin with ifosfamide in treating patients who have advanced or metastatic soft tissue sarcoma, including liposarcoma. This is a dose-escalation study of ifosfamide. Patients receive doxorubicin HCl liposome IV over 1 hour on day 1 and ifosfamide IV over 4 hours on days 1-3 OR on days 1-4 (for patients enrolled on dose level 6). Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of ifosfamide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 3-24 patients will be accrued for this study. Patients 18 to 70 years of age are eligible. This study is being conducted at centers in Denmark and Germany.
This Phase III trial is currently recruiting patients. The purpose of this trial is to compare the effectiveness of combination chemotherapy with or without hyperthermia therapy in treating patients with soft tissue sarcoma, including liposarcoma. Hyperthermia is a type of cancer treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells. Patients are stratified according to risk category and disease site (extremity vs. nonextremity). Patients are randomized to one of two treatment arms. In Arm I: Patients receive etoposide IV over 30 minutes on days 1 and 4, ifosfamide IV over 60 minutes on days 1-4, and doxorubicin IV over 30 minutes on day 1. Treatment continues every 21 days for a total of 4 courses. Patients also undergo regional hyperthermia. In Arm II: Patients receive chemotherapy alone as in arm I. Patients in both arms undergo definitive surgery 4-6 weeks after chemotherapy. Patients also undergo radiotherapy beginning 4-6 weeks after surgery. After completion of surgery and radiotherapy, patients with non-resectable tumors showing no disease progression receive an additional 4 courses of chemotherapy with or without regional hyperthermia according to above treatment schedule. A total of 340 patients (170 patients per arm) will be accrued for this study. Patients 18 to 70 years of age are eligible. This study is being conducted at several centers in Germany.
Vaccine-Related Clinical Trials Vaccine Therapy and Sargramostim in Treating Patients With Sarcoma or Brain Tumor This Phase I trial is currently recruiting patients. Vaccines may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim increase the number of immune cells found in bone marrow or peripheral blood. Combining vaccine therapy with sargramostim may cause a stronger immune response and kill more tumor cells. Thus, the purpose of this trial is to study the effectiveness of combining vaccine therapy with sargramostim in treating patients who have advanced sarcoma, including leiomyosarcoma, synovial cell sarcoma, liposarcoma, glialsarcoma or brain tumor. Patients receive telomerase: 540-548 peptide vaccine subcutaneously (SC) on day 3 and sargramostim (GM-CSF) SC on days 1-4 of weeks 1, 3, 5, 7, 9, 11, 15, 19, and 23. A total of 35 patients (20 adult and 15 pediatric) will be accrued for this study. Patients 2 years of age and older are eligible. This study is being conducted at the Dana-Farber Cancer Institute.
Phase II Clinical Trial Dendritic Cell Vaccine Therapy of Sarcoma Patients Post Stem Cell TransplantationImmunotherapy strategies, specifically dendritic cell (DC) based tumor vaccines, against solid tumors have been shown in pre-clinical and early clinical trials to be safe and produce anti-tumor responses in adults and children. Recent experimental evidence indicates that the period of lymphopenia that occurs after autologous hematopoietic stem cell transplant (HSCT) may be an opportune time to improve the immune response to self tumor antigens. Therefore, consolidation of minimal residual disease (MRD) following autologous HSCT with a DC based tumor vaccine represents a logical and attractive approach for the treatment of sarcoma patients. Patients in this proposed Phase II trial will receive high dose chemotherapy and HSCT followed by a series of three autologous monocyte-derived tumor lysate-pulsed mature DC vaccines. Patients will be assessed for both clinical response and specific immunologic anti-tumor response. Please note the following: the National Institutes of Health/National Cancer Institute review process has not made a decision whether to fund this trial. A decision was expected to be made in August '04. Dr. James D. Geiger, Lead Investigator, Tumor Immunologist and Pediatric Surgeon, and Associate Professor at the University of Michigan Medical School Mott Children's Hospital and his research team will open a "Pilot Study" program that is privately funded to allow patients in dire need to receive treatment much sooner. Under this Pilot Study, patients can be treated on an as-needed-basis. The NIH/NCI proposal depends on public dollars and restricts the treatment period and use of the vaccine. A privately funded "Pilot Study" would allow for adaptations.
This Phase I trial is currently recruiting patients. Radiolabeled monoclonal antibodies can locate tumor cells and deliver radioactive tumor-killing substances, such as radioactive iodine, to them without harming normal cells. The purpose of this trial is to study the effectiveness of radiolabeled monoclonal antibody therapy in treating patients who have refractory, recurrent, or advanced CNS or leptomeningeal cancer. Sarcomas eligible for the trial include Ewing's sarcoma, primitive neuroectodermal tumor, osteosarcoma, and rhabdomyosarcoma. Patients receive iodine I 131 monoclonal antibody 8H9 (131I MOAB 8H9) intrathecally on day 1. Treatment repeats every 4 weeks for up to 2 courses (total of 2 injections) in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of 131I MOAB 8H9 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 3-30 patients will be accrued for this study within 2-3 years. Patients of any age are eligible. The study is being conducted at Memorial Sloan-Kettering Cancer Center, New York, New York.
This Phase II trial is currently recruiting patients. Eradication of low tumor burdens can occur in vivo when T-cell mediated responses are generated against specific tumor antigens. The Ewing's sarcoma family of tumors (ESFT) and alveolar rhabdomyosarcoma (AR) display several features which make them candidate diseases for trials of such immunotherapy. Tumor-specific chromosomal translocations resulting in the production of novel fusion proteins have been identified in the great majority of these tumors. Peptides derived from these fusion proteins have been shown to function as tumor antigens for cytolytic T cells in animal studies. Studies of immune reconstitution after intensive cytotoxic therapy have provided evidence that antigen-specific T cells can be generated in vivo when the adoptive transfer of peripheral T cells and antigen are provided during the period of T cell regeneration. This process can be augmented in murine models by the use of HIV active protease inhibitor, indinavir, potentially through inhibition of programmed cell death in expanding T cells. Thus, this trial will attempt to eradicate minimal residual disease in pediatric patients with metastatic ESFT and AR via vaccination with tumor-specific peptides undertaken concomitant with autologous T cell transplantation and indinavir. The patient’s tumor specimen is analyzed for the presence of a fusion protein which corresponds to available peptides. Patients undergo T cell harvest 10 days after an initial priming peptide-pulsed antigen presenting cell (APC) vaccine is performed. Fresh APCs are utilized for initial priming vaccination. All subsequent vaccinations will use cryopreserved APCs. Patients undergo cytoreductive therapy for the treatment of their particular malignancy. This therapy usually consists of multiagent chemotherapy in the context of a separate protocol. Following chemotherapy, infusion of harvested T cells followed by infusion of peptide-pulsed APC vaccinations occurs every 6 weeks for a total of 3 post-priming vaccinations. Influenza vaccine is administered by intramuscular injection concurrent to peptide-pulsed APC vaccines. IL-2 is administered as a continuous IV infusion for 4 days/week for 3 successive weeks starting on the same day as T cell /peptide-pulsed infusions. The expected enrollment for this study is 45 patients. Patients must be less than or equal to 35 years at the time of initial diagnosis. The study is being conducted at the National Cancer Institute.
Chemotherapy With or Without Trastuzumab in Treating Patients With Metastatic OsteosarcomaThis Phase II trial is currently recruiting patients. The purpose of this trial is to study the effectiveness of chemotherapy with or without the monoclonal antibody trastuzumab in treating patients who have metastatic osteosarcoma. Patients are stratified according to tumor status (positive vs. negative). Patients receive induction therapy comprising doxorubicin IV over 20 minutes followed by cisplatin IV over 4 hours on days 1 and 2 of weeks 1 and 6, and methotrexate IV over 4 hours on day 1 of weeks 4, 5, 9, and 10. Patients also receive leucovorin calcium IV or orally every 6 hours beginning 24 hours after each methotrexate dose and continuing for at least 10 doses until methotrexate levels sufficiently decrease. Within 24-36 hours after completion of induction therapy, patients receive filgrastim (G-CSF) daily until blood counts recover. Patients undergo resection of any remaining primary tumor and/or metastatic lesions during week 11. Patient who are unable to undergo resection receive radiotherapy between weeks 11 and 17. Patients receive post-induction therapy comprising doxorubicin IV over 20 minutes on days 1 and 2 of weeks 17, 25, and 29; cisplatin IV over 4 hours on days 1 and 2 of weeks 17 and 25; methotrexate IV over 4 hours on day 1 of weeks 16, 20, 24, 28, 32, and 33; etoposide IV over 1 hour on days 1-5 of weeks 13, 21, and 34; and ifosfamide IV over 4 hours on days 1-5 of weeks 13, 21, 29, and 34. Patients also receive leucovorin calcium and G-CSF as in induction therapy. Patients whose tumors are found to over express HER2 (2+ level of expression) also receive trastuzumab IV over 30-90 minutes once a week for a total of 34 weeks in addition to the chemotherapy regimen. Patients are followed monthly for 1 year, every 2 months for 1 year, every 6 months for 2 years, and then annually thereafter. A total of 80 patients (40 patients per stratum) will be accrued for this study within 2.5 years. Patients up to 30 years of age are eligible. This is a multi-center study, which includes centers in Australia, Canada, New Zealand, Netherlands, Puerto Rico and Switzerland.
V1N5 ESUN Copyright © 2004 Liddy Shriver Sarcoma Initiative.
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