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 stage IIC or stage III soft tissue sarcoma.

OBJECTIVES:

• Determine the maximum tolerated dose of SU5416 when administered with neoadjuvant chemotherapy and radiotherapy and adjuvant chemotherapy in patients with high-grade stage IIC-III soft tissue sarcoma.
• Determine the disease-free survival, local control, and overall survival in patients treated with this regimen.
• Determine histological response in patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.
• Determine the quantitative antiangiogenic effects of SU5416 in patients treated with this regimen.

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.

• Biological: filgrastim
• Drug: dacarbazine
• Drug: doxorubicin hydrochloride
• Drug: ifosfamide
• Drug: semaxanib
• Procedure: conventional surgery
• Radiation: radiation therapy

DISEASE CHARACTERISTICS:

• Histologically confirmed stage IIC-III primary or locally recurrent soft tissue sarcoma

  • Grade 2 or 3 on grade 1-3 scale OR
  • Grade 3 or 4 on grade 3-4 scale
  • Tumor size at least 8 cm in diameter
• 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

  • Lesions no greater than 1 cm in diameter allowed if stable for at least 1 year and fit criteria for granulomas

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 150,000/mm^3
• No prior bleeding or clotting diathesis

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• AST and ALT no greater than 1.5 times upper limit of normal
• PT and PTT less than 1.25 times normal (not on coumadin)

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• LVEF greater than 50%
• History of atherosclerotic coronary artery disease (CAD) requiring bypass surgery allowed provided surgery occurred at least 1 year prior to study entry
• No uncompensated CAD on electrocardiogram or physical examination
• No myocardial infarction or severe or unstable angina within the past 6 months
• No New York Heart Association class II-IV heart disease
• No congestive heart failure
• No severe peripheral vascular disease
• No peripheral vascular disease with diabetes mellitus
• No deep venous or arterial thrombosis (including pulmonary embolism) within the past 3 months

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Fibrin split products less than 2 times normal
• Fibrinogen greater than 200 mg/dL
• No active uncontrolled bacterial, viral, or fungal infection
• No known hypersensitivity to E. coli-derived proteins
• No contraindications to limb-salvage surgery
• No other prior or concurrent malignancy within the past 5 years except surgically treated carcinoma in situ of the cervix or squamous or basal cell skin cancer
• No other serious medical or psychiatric illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior biologic therapy

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• More than 2 weeks since minor surgery
• More than 4 weeks since major surgery