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 solid tumors that have not responded to previous therapy.

Condition	Treatment or Intervention	Phase
unspecified adult solid tumor, protocol specific	Drug: combretastatin A4 phosphate	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the maximum tolerated dose of combretastatin A4 phosphate when administered at single doses every 21 days in patients with advanced solid tumors. II. Determine both the toxicity and dose limiting toxicity of this regimen in these patients. III. Determine the plasma and urine pharmacokinetics of combretastatin A4 and combretastatin A4 phosphate. IV. Gather preliminary data regarding possible antitumor effects in those patients with measurable disease.

PROTOCOL OUTLINE: This is an open label, dose escalation study. Patients receive combretastatin A4 phosphate IV over 10-60 minutes. Treatment repeats every 3 weeks in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of combretastatin A4 phosphate 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 at 3 weeks.

PROJECTED ACCRUAL: A maximum of 21 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically or cytologically proven advanced solid tumors that have failed standard therapy or for which no curative therapy exists; No leukemia, lymphoma, or multiple myeloma
• No brain metastases

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks for mitomycin and nitrosoureas) and recovered; No other concurrent cytotoxic therapy
• Endocrine therapy: Not specified
• Radiotherapy: At least 4 weeks since prior radiotherapy and recovered
• Surgery: At least 6 weeks since prior major surgery
• Other: At least 4 weeks since any other prior investigational agent; No concurrent anticonvulsant therapy; No concurrent aspirin greater than 100 mg per day, heparin, or nonsteroidal antiinflammatory medication; No concurrent calcium channel blockers, antiarrhythmias, or anti-angina therapy; Concurrent beta-blocking agents for hypertension or anxiety allowed

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-2
• Life expectancy: At least 12 weeks
• Hematopoietic: WBC at least 3,000/mm3; Granulocyte count at least 1,500/mm3; Platelet count at least 100,000/mm3; Hemoglobin at least 9.0 g/dL
• Hepatic: Bilirubin normal; SGOT/SGPT no greater than 3 times upper limit of normal (ULN); PT/PTT less than ULN OR International normalized ratio (INR) less than 1.1
• Renal: Creatinine no greater than 2.0 mg/dL OR Creatinine clearance greater than 60 mL/min
• Cardiovascular: No clear evidence of acute ischemic heart disease on EKG; No history of myocardial infarction within past 6 months; No history of angina; No peripheral vascular disorder
• Neurologic: No active seizure disorder
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception; No evidence of hematemesis, melena, or hematochezia; No history of inflammatory bowel disease, autoimmune disease, or bleeding disorders; No Type I diabetes mellitus or Type II diabetes with peripheral vascular disorders; No active infections or any serious concurrent systemic disorders incompatible with study

Ohio
      Ireland Cancer Center, Cleveland,  Ohio,  44106-5065,  United States

Study chairs or principal investigators

Scot C. Remick,  Study Chair,  Ireland Cancer Center   

Study ID Numbers:  CDR0000066894; CWRU-ILEX-1Y98; NCI-G99-1502; ILEX-1Y98; ILEX-CA4P101-A3
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  April 6, 2000
ClinicalTrials.gov Identifier:  NCT00003768
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08