Radiation Therapy With or Without SU5416 in Treating Patients With Soft Tissue Sarcoma

OBJECTIVES:

• Determine the maximum tolerated dose of SU5416 when combined with neoadjuvant radiotherapy in patients with stage IB or IIA soft tissue sarcoma.
• Determine the antiangiogenic effects of SU5416 in these patients.
• Determine any synergistic antiangiogenic effect of SU5416 with radiotherapy in these patients.
• Compare the disease-free survival, local recurrence, distant metastases, and overall survival rates in patients treated with neoadjuvant radiotherapy with or without SU5416.

OUTLINE: This is a phase I dose-escalation study of SU5416 followed by a phase II randomized study.

Phase I:

• Patients undergo radiotherapy once daily, 5 days a week, for 5 weeks. Patients also receive SU5416 IV over 1 hour twice weekly beginning on week 1 and continuing until 2 days before surgery.
• 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.

Phase II:

• Once the MTD has been determined, additional patients are accrued and then randomized to receive either treatment as in phase I at the MTD vs preoperative radiotherapy alone.

All patients undergo surgical resection 70-80 days after beginning therapy. Patients with positive surgical margins receive additional radiotherapy daily for 8 days and SU5416 IV over 1 hour on days 2, 4, and 9.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 18 patients will be accrued for phase I of this study within 1 year. Approximately 28 patients will be accrued for phase II of this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed primary or locally recurrent stage IB or IIA soft tissue sarcoma

• Grade 1 or 2
• Tumor greater than 5 cm in diameter
• Tumor located on upper extremities (including shoulder), lower extremities (including hip), or body wall
• No sarcoma of the head and neck or intra-abdominal or retroperitoneal sarcoma
• No desmoid tumor or dermatofibrosarcoma protuberans
• No metastatic disease
• No evidence of lung metastases

• Maximum of 4 lung lesions no greater than 5 mm in diameter each on preoperative chest CT scan allowed OR
• Lesion no greater than 1 cm allowed if stable for at least 1 year and fits criteria for granuloma

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Zubrod 0-1

Life expectancy:

• At least 2 years

Hematopoietic:

• WBC at least 4,000/mm^3 OR
• Absolute neutrophil count at least 1,800/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGOT no greater than 50 U/L
• PT and PTT less than 1.25 times normal (not on warfarin)

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance greater than 50 mL/min

Cardiovascular:

• No congestive heart failure or myocardial infarction within the past 6 months
• No uncompensated coronary artery disease
• No severe peripheral vascular disease
• No peripheral vascular disease with diabetes mellitus
• No deep venous or arterial thrombosis within the past 3 months
• Fibrin split products less than 2 times normal
• Fibrinogen greater than 200 mg/dL

Pulmonary:

• No pulmonary embolism within the past 3 months

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No contraindications to surgery
• No active uncontrolled bacterial, viral, or fungal infection
• No other prior or concurrent malignancy within the past 5 years except surgically treated carcinoma in situ of the cervix or squamous cell or basal cell skin cancer
• No other serious medical or psychiatric illness that would preclude informed consent

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior biologic therapy for soft tissue sarcoma

Chemotherapy:

• No prior chemotherapy for soft tissue sarcoma

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy for soft tissue sarcoma

Surgery:

• At least 2 weeks since prior minor surgery (e.g., port placement)
• At least 4 weeks since prior major surgery