COL-3 in HIV associated Kaposi's Sarcoma

Massachusetts General Hospital, Boston MA

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Abstract

This study is to determine the safety and toxicity of COL-3 in subjects with HIV-related KS; to evaluate the tumor response rate of treatment with COL-3 in subjects with HIV related KS; to evaluate the effects of COL-3 on CD4 and CD8 cell counts and percentages as well as on viral load; to characterize the pharmacokinetics of COL-3; to describe the relationship between tumor response and serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF); to evaluate the effect of COL-3 on serum levels of MMP-2 and MMP-9 and to evaluate the effects of serum from COL-3 treated subjects on angiogenesis using a rat angiogenesis model or other model of matrix metalloproteinaise inhibiton. KS is most common malignancy occurring in the setting of HIV infection. It is estimated that 20-30% of infected people will develop KS. To date, therapy has focused on immunologic modulation with interferon and systemic chemotherapy with various agents. Although not curative, these therapies are effective in palliating symptoms but are associated with multiple toxicities, including bone marrow suppression. Therefore, new and potentially less toxic agents are needed to treat this disease. Vascular endothelial proliferation and rapid formation of new blood vessels is necessary to the pathophysiology of KS. Therefore novel agents which inhibit this process could be potentially be useful in the treatment of KS. COL-3 is a chemically modified tetracycline that appears to inhibit the development of blood vessels that are essential for the tumor to grow.