A Phase I/II Study Of Neoadjuvant Chemotherapy, Angiogenesis Inhibitor SU5416 (NSC # 696819; A TK Inhibitor Anti-Angionesises Compound), And Radiation Therapy In The Management Of High Risk, High-Grade, Soft Tissue Sarcomas Of The Extremities And Body Wall
A Phase I/II Study Of Neoadjuvant Chemotherapy, Angiogenesis Inhibitor SU5416 (NSC # 696819; A TK Inhibitor Anti-Angionesises Compound), And Radiation Therapy In The Management Of High Risk, High-Grade, Soft Tissue Sarcomas Of The Extremities And Body Wall
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Drugs such as SU5416 may stop the growth of cancer by stopping blood flow to the tumor. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving chemotherapy, SU5416, and radiation therapy before and after surgery may kill more tumor cells.
PURPOSE: Phase I/II trial to study the effectiveness of chemotherapy, SU5416, radiation therapy, and surgery in treating patients who have soft tissue sarcoma.
OBJECTIVES:
OUTLINE: This is a dose-escalation study of SU5416.
Patients receive neoadjuvant chemotherapy comprising doxorubicin, ifosfamide, and dacarbazine IV continuously on days 1-3, 22-24, and 43-45. Patients also receive filgrastim (G-CSF) subcutaneously once daily beginning on day 5 and continuing until blood counts recover. Patients undergo 2 courses of radiotherapy, given once daily for 11 doses per course over days 7-20 and 28-41. Patients also receive SU5416 IV over 1 hour twice weekly beginning on day 1 and continuing until 2 days before surgery. Patients undergo surgical resection on day 80. Patients then receive adjuvant chemotherapy comprising doxorubicin, ifosfamide, and dacarbazine IV continuously on days 101-103, 122-124, and 143-145. Patients also receive SU5416 IV over 1 hour twice weekly beginning on day 101 and continuing until the end of adjuvant chemotherapy. Patients with positive surgical margins receive additional radiotherapy beginning 2 weeks after resection for a total of 8 doses.
Cohorts of 3-6 patients receive escalating doses of SU5416 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.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: Approximately 68-80 patients will be accrued for this study.
DISEASE CHARACTERISTICS:
Histologically confirmed stage IIC-III primary or locally recurrent soft tissue sarcoma
Tumor located on upper extremities (including shoulder), lower extremities (including hip), or on body wall
No rhabdomyosarcoma, extraosseous Ewing's sarcoma, primitive neuroectodermal tumors, osteosarcoma or chondrosarcoma, Kaposi's sarcoma or angiosarcoma of the scalp or face, or any sarcoma of the head and neck
No evidence of lung metastases
Maximum of 4 chest lesion no greater than 3 mm in diameter each on preoperative chest CT scans
PATIENT CHARACTERISTICS:
Age:
Performance status:
Life expectancy:
Hematopoietic:
Hepatic:
Renal:
Cardiovascular:
Other:
PRIOR CONCURRENT THERAPY:
Biologic therapy:
Chemotherapy:
Endocrine therapy:
Radiotherapy:
Surgery:
Birmingham, Alabama 35294-3300, United States
Tuscallosa, Alabama 35401, United States
Duarte, California 91010-3000, United States
Los Angeles, California 90033-0804, United States
Indianapolis, Indiana 46202, United States
Indianapolis, Indiana 46219, United States
Lexington, Kentucky 40536-0084, United States
Baltimore, Maryland 21231-2410, United States
Jamaica Plain, Massachusetts 02130, United States
Mount Holly, New Jersey 08060, United States
Brooklyn, New York 11203, United States
Syracuse, New York 13217, United States
Winston-Salem, North Carolina 27157-1082, United States
Philadelphia, Pennsylvania 19107-5541, United States
St. John's, Newfoundland and Labrador A1B 3V6, Canada