A Phase II Study of CCI-779 in Combination With Bevacizumab in Stage III or IV Melanoma
I. Determine the objective tumor response rate (complete response and partial response) in
patients with stage III or IV melanoma treated with temsirolimus and bevacizumab.
I. Describe the adverse event profile of this regimen in these patients. II. Determine the
efficacy of this regimen, in terms of progression-free survival, in these patients.
III. Compare pre- vs post-treatment measurements of biomarkers and vascular system/immune
system parameters in patients treated with this regimen.
IV. Correlate tumor and blood biomarkers with clinical response in these patients.
OUTLINE: This is a multicenter study.
Patients receive temsirolimus intravenously (IV) over 30 minutes on days 1 and 8 and
bevacizumab IV over 30-90 minutes on day 8. Treatment repeats every 14 days for a maximum of
26 courses in the absence of disease progression or unacceptable toxicity. Patients undergo
tumor resection on day 9 of course 2.Blood samples are collected during courses 1 and 2.
Samples are examined by flow cytometry to evaluate peripheral blood mononuclear cells for
molecular effects of study agents. Patients also undergo normal and tumor tissue biopsy (by
core needle biopsy, incisional biopsy, or surgical resection) during courses 1 and 2.
Samples are examined by immunohistochemistry, western blotting, protein array technology,
gene expression analyses, DNA mutation analyses, and genomic analyses for pre-and
post-treatment measurements of target molecules (epidermal growth factor receptor, B-Raf,
MEK, MAPK), downstream pathway components (PI-3 kinase, AKT, mTOR), markers of angiogenesis,
proliferation and apoptosis, markers that may modulate cell signaling or the response to
investigational agents, and vascular and immune system parameters.
After completion of study treatment, patients are followed at 1 month, every 3 months for up
to 2 years, and then periodically for up to 5 years.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Objective tumor response (complete response and partial response) and progression in participants with stage III or IV melanoma following treatment with temsirolimus and bevacizumab
Evaluated using Response Evaluation Criteria In Solid Tumor (RECIST) criteria.
Day 11 of courses 4, 8, 12, 16, 20, and 24
University of Virginia
United States: Food and Drug Administration
|Fox Chase Cancer Center||Philadelphia, Pennsylvania 19111|
|University of Virginia||Charlottesville, Virginia 22908|