RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of combretastatin A4 phosphate in treating patients who have advanced malignant solid tumors .

OBJECTIVES: I. Determine the toxicity profile, including dose limiting toxicity, and maximum tolerated dose (MTD) of combretastatin A4 phosphate in patients with advanced solid malignant tumors. II. Determine the pharmacokinetics of combretastatin A4 phosphate. III. Assess the effects of combretastatin A4 phosphate on tumor blood flow using PET and MRI scanning techniques, and establish the dose at which these effects occur. IV. Recommend a dose of combretastatin A4 phosphate for phase II evaluation based on tumor blood flow effect and the MTD. V. Evaluate possible antitumor effects of this regimen in these patients.

PROTOCOL OUTLINE: This is an open label, dose escalation, multicenter study. Patients receive IV combretastatin A4 phosphate over 10 minutes once a week for 3 weeks. Patients not experiencing unacceptable toxic effects begin individual dose escalation, receiving a maximum of 3 dose levels with 2 weeks of rest between each dose level. Dose escalation stops when 2 patients have experienced dose limiting toxicity (DLT) at a particular dose level. Once DLT is established, at least 6 patients are treated at a lower dose to determine the maximum tolerated dose. Patients may receive up to 6 courses of 3 infusions each. Patients are followed for 4 weeks.

PROJECTED ACCRUAL: Approximately 30-35 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed solid tumor that is not amenable to any standard curative therapy or is refractory to conventional therapy
• Tumor suitable for MRI or PET imaging
• No active brain metastases

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: At least 6 weeks since prior nitrosoureas or mitomycin and recovered
• Endocrine therapy: Concurrent steroid use allowed
• Radiotherapy: At least 6 weeks since prior radiotherapy (except radiotherapy to small isolated fields not including significant areas of bone marrow) and recovered; No prior radiotherapy to tumor site(s) that will be imaged by MRI/PET scanning or used to assess tumor response
• Surgery: No concurrent open surgery
• Other: At least 4 weeks since all other prior anticancer therapies and recovered; No concurrent heparin or warfarin; Concurrent NSAIDs allowed

--Patient Characteristics--

• Age: 18 and over
• Performance status: WHO 0-2
• Life expectancy: At least 4 months
• Hematopoietic: WBC at least 4,000/mm3; Platelet count at least 100,000/mm3; Hemoglobin at least 10 g/dL
• Hepatic: Bilirubin less than 1.17 mg/dL; ALT or AST less than 2 times upper limit of normal; (ULN) Alkaline phosphatase less than 2 times ULN (unless due to liver or bone metastases)
• Renal: Creatinine less than 1.5 mg/dL
• Cardiovascular: No ischemic heart disease
• Other: Not pregnant or nursing; Fertile patients must use effective contraception at least 4 weeks before, during, and for 4 weeks after the study; No other serious medical condition or serious infection within past 28 days; No other active concurrent malignancies, except: Carcinoma in situ of the cervix Adequately treated basal or squamous cell carcinoma of the skin; No autoimmune disorders; No inflammatory bowel disease; No diabetes