Phase II Study of Intravenous Recombinant Humanized Anti-Vascular Endothelial Cell Growth Factor Antibody (Bevacizumab) in Classical (HIV-Negative) and in AIDS-Associated Kaposi's Sarcoma
This is a phase II study to determine the activity of bevacizumab, a putative antiangiogenic
agent, in Kaposi's sarcoma (KS). Bevacizumab is a humanized recombinant antibody to vascular
endothelial cell growth factor (VEGF), an important cytokine in the pathogenesis of KS.
To assess the antitumor effect of bevacizumab 15 mg/kg administered intravenously once every
three weeks in patients with human immunodeficiency virus (HIV)-associated Kaposi's sarcoma
(KS). Other objectives include assessment of the antitumor effect of bevacizumab 15 mg/kg
administered intravenously once every three weeks in patients with classical KS; assessment
of the toxicity profile of bevacizumab in HIV-infected and HIV-negative patients with KS;
exploration in a preliminary fashion effect of bevacizumab on KS progression free survival;
and study of a number of biochemical parameters, including stromal cell-derived factor-1
(SDF-1) expression in KS lesions; human herpes virus-8 (HHV-8) viral load in peripheral
blood mononuclear cells; serum vascular endothelial growth factor (VEGF) levels over the
course of treatment; and changes in viral interleukin 6 (IL-6) levels over the course of
Key eligibility parameters include HIV-associated or classical Kaposi's sarcoma, age greater
than or equal to 18 years, and life expectancy greater than 6 months. Patients with HIV
infection must have either KS progression on a regimen of highly active antiretroviral
therapy (HAART) for at least one month, or no KS regression while on an optimized regimen of
HAART for 4 months or longer.
Patients will be sequentially enrolled, administered a loading dose of 15 mg/kg bevacizumab
intravenously on day 1, and then administered 15 mg/kg bevacizumab intravenously every 3
weeks beginning one week after the loading dose. The drug will be temporarily discontinued
for toxicity, intercurrent major surgical procedures, or other factors that would pose a
safety concern. Patients will undergo a biopsy of a KS lesion at entry, on cycle 4, day 21,
and at the time of a formal response or when the patient stops treatment. Patients will
undergo a number of other tests as well, including blood tests and non-invasive imaging
studies of KS lesions.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Percentage of participants with a complete response (CR) + partial response (PR)per the Modified AIDS Clinical Trial Group Criteria (ACTG) for HIV-KS. PR is a 50% decrease in the number and/or size of previously existing lesions for 4 weeks; or complete flattening of at least 50% of all previously raised lesions lasting for at least 4 weeks; or a 50% decrease in the sum of the products of the largest perpendicular diameters of the marker lesions lasting for at least 4 weeks; CR is the absence of any detectable residual disease, including tumor associated edema, persisting for at least 4 weeks.
Robert Yarchoan, M.D.
National Cancer Institute, National Institutes of Health
United States: Federal Government
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