Temsirolimus and Bevacizumab in Treating Patients With Stage III or Stage IV Malignant Melanoma
This phase II trial is studying how well giving temsirolimus together with bevacizumab works in treating patients with stage III or stage IV malignant melanoma. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of malignant melanoma by blocking blood flow to the tumor. Giving temsirolimus together with bevacizumab may kill more tumor cells.
Stage IIIA Skin Melanoma
Stage IIIB Skin Melanoma
Stage IIIC Skin Melanoma
Stage IV Skin Melanoma
Procedure: Therapeutic Conventional Surgery
Other: Laboratory Biomarker Analysis
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of CCI-779 in Combination With Bevacizumab in Stage III or IV Melanoma|
- Objective tumor response (complete response and partial response) and progression in participants with stage III or IV melanoma following treatment with temsirolimus and bevacizumab [ Time Frame: Day 11 of courses 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]Evaluated using Response Evaluation Criteria In Solid Tumor (RECIST) criteria.
- Adverse events in participants with stage III or IV melanoma treated with temsirolimus and bevacizumab [ Time Frame: Days 1 and 8 of each course ] [ Designated as safety issue: Yes ]Defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome, or disease which either occurs during the study (having been absent at baseline) or if present at baseline, appears to worsen. Graded using scales found in the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Tabulated by type and severity.
- Progression-free survival [ Time Frame: Day 11 of courses 4, 8, 12, 16, 20, and 24, and then annually for up to 5 years ] [ Designated as safety issue: No ]Defined as the duration of time from start of treatment to time of progression, death or date of last follow-up.
- Comparison of pre- vs post-treatment measurements of biomarkers and vascular system/immune system parameters [ Time Frame: Day 1 of course 1 and day 8 of course 2 ] [ Designated as safety issue: No ]Biomarker expression in tumor and normal skin will be assessed by immunohistochemistry (IHC) or Western blotting, using marker-specific antibodies.
- Association between expression or activation of one biomarker with another, with biochemical and clinical responses, with alterations in cell proliferation and apoptotic markers, and with time to progression [ Time Frame: Day 1 of course 1 and day 8 of course 2 ] [ Designated as safety issue: No ]Biomarker expression in tumor and normal skin will be assessed by IHC or Western blotting, using marker-specific antibodies.
- Comparison of biomarkers to antitumor activity/patient outcomes [ Time Frame: Day 1 of course 1 and day 8 of course 2 ] [ Designated as safety issue: No ]Assessed in both tumor tissue and in serum/plasma samples.
|Study Start Date:||May 2007|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (enzyme inhibitor, monoclonal antibody)
Patients receive temsirolimus 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.
Procedure: Therapeutic Conventional Surgery
Undergo tumor resectionBiological: Bevacizumab
Other Names:Drug: Temsirolimus
Other Names:Other: Laboratory Biomarker Analysis
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00397982
|United States, Pennsylvania|
|Fox Chase Cancer Center|
|Philadelphia, Pennsylvania, United States, 19111|
|United States, Virginia|
|University of Virginia|
|Charlottesville, Virginia, United States, 22908|
|Principal Investigator:||Craig Slingluff||University of Virginia|