A Phase I Trial of Combretastatin A4 Phosphate in Patients With Solid Tumours Given by Weekly Intravenous Infusion
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.
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.
Primary Purpose: Treatment
Gordon J.S. Rustin, MD
Mount Vernon Cancer Centre at Mount Vernon Hospital
United States: Federal Government