All solid tumors above 1-2 mm in diameter need their own vasculature for continued growth. Tumor cells are known to release factors which cause endothelial cells to divide, and migrate into the tumor mass, leading to the formation of new blood vessels, or angiogenesis. Vascular targeting is an alternative approach to antiangiogenic cancer therapy, aiming to exploit differences between tumor and normal vessels and to produce a rapid and irreversible shutdown (or occlusion) of tumor-specific blood vessels. Combretastatin A4 (CA4) is a novel, natural product tubulin inhibitor that was isolated from the South African tree Combretum caffrum. CA4P (the disodium phosphate formulation developed by OXiGENE Inc) has exhibited both in vitro and in vivo activity against tumor cells. The primary objective of this study is 1) to determine the maximum tolerated dose of CA4P in patients with malignant diseases (solid tumors) in advanced stages when administered at single doses every 21 days. The secondary objectives are: 1) to determine both the toxicity and dose-limiting toxicity of CA4P, 2) to determine the plasma pharmacokinetics of CA4P, 3) to gather preliminary data regarding possible antitumor effects in those patients with measurable disease and 4) to evaluate the effects of CA4P on tumor blood flow at MTD when possible. This is a Phase I, open-label, dose-escalating study of CA4P in patients with solid tumors who have failed standard therapy or for whom no such therapy exists. Patients will be enrolled at increasing dose levels to assess the safety of CA4P. At each dose level, patients will receive a single IV administration of CA4P repeated every 21 days. Blood and urine samples will be collected at each dose level to characterize the pharmacokinetics of CA4P during cycle 1. GCRC nurses will administer the drug, monitor the subjects for side effects, collect required pharmacokinetic samples, and perform couplex sample processing. The protocol requires that this drug be administered only under yellow lights, and that all blood and urine samples must be collected and processed in the presence of only yellow lights.
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