This phase I/II trial studies the side effects and best dose of pazopanib hydrochloride and bevacizumab and to see how well they work in treating patients with previously untreated kidney cancer that has spread to other places in the body (metastatic). Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Pazopanib hydrochloride may also stop the growth of tumor cells by blocking blood flow to the tumor. Monoclonal antibodies, such as bevacizumab, can prevent tumor growth by blocking the ability of tumor cells to grow and spread. Giving pazopanib hydrochloride together with bevacizumab may kill more tumor cells.
PRIMARY OBJECTIVES: * I. To determine the safe phase II dose of this novel regimen. (Phase I) * II. To determine the median progression free survival (PFS) from this novel regimen. (Phase II) SECONDARY OBJECTIVES: * To evaluate the safety and toxicity of the proposed regimen. (Phase I) * To evaluate the response rate. (Phase I) * To evaluate the pharmacokinetics of pazopanib (pazopanib hydrochloride). (Phase I) * To evaluate the vascular endothelial growth factor (VEGF) levels and myeloid derived suppressor cell (MDSC) levels at various time points and correlate with response. (Phase I) * To evaluate the safety and toxicity of this new regimen. (Phase II) * To evaluate the VEGF levels, interleukin (IL)-8 levels and MDSC levels at various time points and correlate with outcome. (Phase II) * To evaluate the PFS rate at 12 months. (Phase II) * To evaluate overall survival. (Phase II) OUTLINE: This is a phase I, dose-escalation study followed by a phase II study. Patients receive pazopanib hydrochloride orally (PO) on days 1-28, and bevacizumab intravenously (IV) over 30-90 minutes on days 36 and 50. Courses repeat every 70 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and Phase II patients are followed up by telephone every 12 months
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
51
The University of Kansas Cancer Center
Westwood, Kansas, United States
Karamanos Cancer Institute
Detroit, Michigan, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Median PFS (Phase II)
Distributions of continuous variables will be summarized with commonly used statistics (mean, standard deviation, median, etc.), with sub-group associations tested using the Wilcoxon Rank Sum test.
Time frame: Up to 30 days post-treatment
Optimal phase II dose, defined as the largest dose level at which less than 2 out of the 6 patients experienced dose-limiting toxicity, graded according to Common Terminology Criteria for Adverse Events version 4.0 (Phase I)
The frequency of toxicities will be tabulated for the dose estimated to be the maximum-tolerated dose.
Time frame: Up to 140 days
Incidence of grade 3 or higher toxicities, graded according to CTCAE version 4.0
Categorical variables will be summarized in contingency tables, with associations of interest assessed using Fisher's exact test. The frequency of toxicities will be tabulated by grade across all dose levels and courses.
Time frame: Up to 30 days post-treatment
Overall survival (Phase II)
Will be obtained using Kaplan-Meier and Proportional Hazards methods.
Time frame: From the date of study enrollment to the date of death from any cause, assessed up to 30 days post-treatment
PFS rate at 12 months (Phase II)
Distributions of continuous variables will be summarized with commonly used statistics (mean, standard deviation, median, etc.), with sub-group associations tested using the Wilcoxon Rank Sum test.
Time frame: At 12 months
Response rate according to RECIST 1.1 (Phase I)
Time frame: Up to 30 days post-treatment
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