Sunitinib Malate and Bevacizumab in Treating Patients With Kidney Cancer or Advanced Solid Malignancies
This phase I trial studies the side effects and the best dose of sunitinib malate when given together with bevacizumab in treating patients with kidney cancer or advanced solid malignancies. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor to grow and spread. Others find tumor cells and help kill them or carry cancer-killing substances to them. Giving sunitinib malate together with bevacizumab may kill more tumor cells.
Clear Cell Renal Cell Carcinoma
Recurrent Renal Cell Cancer
Stage I Renal Cell Cancer
Stage II Renal Cell Cancer
Stage III Renal Cell Cancer
Stage IV Renal Cell Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: sunitinib malate
Other: pharmacological study
Other: laboratory biomarker analysis
Other: fluorine F 18 fluorothymidine
Procedure: positron emission tomography
Procedure: computed tomography
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Pharmacodynamic Trial of Sequential Sunitinib With Bevacizumab in Patients With Renal Cell Carcinoma and Other Advanced Solid Malignancies|
- Proportion of patients with grade 3 or higher toxicities and recommended phase II dose of sunitinib in the presence of bevacizumab or sunitinib alone graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
- Objective response rate using the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Responses will be summarized using descriptive statistics and frequency tables. Two-sided 95% confidence intervals for the proportions of subjects with a confirmed anti-tumor response will be computed for the two treatment schedules of sunitinib malate
- Pharmacodynamic change in SUV peak and tumor perfusion using FLT PET/CT [ Time Frame: Baseline, at 4 weeks and 6 weeks of course 1 ] [ Designated as safety issue: No ]Summarized in terms of means, standard deviations and ranges. Percentage changes will be computed and formally compared using paired t-tests and/or the nonparametric Wilcoxon Signed Rank test, should the normality assumption be violated.
- Changes in the ration of free-bound plasma VEGF by Enzyme-linked immuno sorbent assay (ELISA) [ Time Frame: Baseline to 2 years ] [ Designated as safety issue: No ]Plasma VEGF will be summarized using descriptive statistics such as means, standard deviations and ranges. Changes from baseline will be evaluated using paired t-tests and/or nonparametric Wilcoxon Signed Rank tests, should the normality assumption be violated and should no normality-improving transformation be found
|Study Start Date:||October 2010|
|Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Experimental: Treatment (sunitinib malate, bevacizumab)
Patients receive sunitinib malate PO on days 1-28 and bevacizumab IV over 30-90 minutes on day 29. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Drug: sunitinib malate
Given POBiological: bevacizumab
Given IVOther: pharmacological study
Correlative studiesOther: laboratory biomarker analysis
Correlative studiesOther: fluorine F 18 fluorothymidine
Undergo FLT PET/CTProcedure: positron emission tomography
Undergo FLT PET/CTProcedure: computed tomography
Undergo FLT PET/CT
I. To evaluate the safety and tolerability of sequential sunitinib (sunitinib malate) with bevacizumab in patients with clear cell kidney cancer.
II. To assess the objective response rate of sequential sunitinib with bevacizumab in patients with clear cell kidney cancer.
I. To determine the pharmacodynamic change in standardized uptake values (SUV) peak and tumor perfusion using fluorine F 18 fluorothymidine positron emission tomography (FLT-PET)/computed tomography (CT) scans at baseline, during sunitinib exposure, and during bevacizumab exposure (during sunitinib withdrawal period) in patients with renal cell and other solid malignancies.
II. To characterize changes in the ratio of free: bound plasma vascular endothelial growth factor (VEGF) in patients treated with sequential sunitinib with bevacizumab.
OUTLINE: This is a dose-escalation study of sunitinib malate.
Patients receive sunitinib malate orally (PO) on days 1-28 and bevacizumab intravenously (IV) over 30-90 minutes on day 29. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics|
|Madison, Wisconsin, United States, 53792|
|Principal Investigator:||Glenn Liu||University of Wisconsin Hospital and Clinics|