PHASE I STUDY OF ENDOSTATIN IN ADVANCED CANCER PATIENTS

$0M01FY2000RRNIH

University Of Wisconsin Madison, Madison WI

Investigators

Linked publications & trials

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Abstract

The ability of malignant cancers to grow is dependent on the acquisition of new blood vessels, a process termed angiogenesis. Angiogenesis is a complex process resulting in the sprouting of new vessels from existing vessels that requires the orchestration of vascular basement membrane degradation, endothelial cell migration, endothelial cell proliferation, capillary tube formation and finally differentiation into a mature vessel. Without this angiogenic process, primary tumors and their metastasis remain small and dormant. Tumor angiogenesis is thought to occur by either the increase in angiogenic factors such as vascular endothelial growth factor (VEGF) or the decrease in endogenous inhibitors of angiogenesis. Inhibition of angiogenesis as a method to prevent tumor growth is currently an area of intense investigation. Agents that inhibit angiogenesis represent a new class of anti-neoplastic compounds. Endostatin is a naturally-occurring peptide that has shown to inhibit angiogenesis. We are proposing within this clinical trial to administer Endostatin as an intravenous infusion for one hour every day for 28 days. The mechanism of action is unknown and for thus reason it is an active area of investigation. Hypothesis for its mechanism include its interference with bFGF signaling and that Endostatin binds strongly to epithelial basement membranes. Endostatin has also shown to induce endothelial cell apoptosis, and it has also been shown to bind to zinc. Within this clinical trial we will measure the angiogenesis properties of Endostatin through PET scanning, serial tumor biopsies, ultrasounds, and magnetic resonance imaging. Endostatin will be given as a one hour intravenous infusion. The rational for multiple daily administration comes from initial studies with C57B1/6 mice containing subcutaneously implanted tumors. This schedule was able to induce regressions and sustained tumor dormancy.

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