This randomized phase III trial studies giving everolimus together with bevacizumab to see how well it works compared to everolimus alone in treating patients with advanced kidney cancer that progressed after first-line therapy. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can interfere with tumor growth by blocking the ability of tumor cells to grow and spread. Everolimus and bevacizumab may also stop the growth of kidney cancer by blocking blood flow to the tumor. It is not yet known whether giving everolimus together with bevacizumab is better than everolimus alone in treating patients with advanced kidney cancer that has progressed after first-line therapy.
PRIMARY OBJECTIVES: l. To compare the overall survival of patients receiving bevacizumab plus everolimus and everolimus alone among patients with advanced renal cell carcinoma progressing after first line vascular epidermal growth factor receptor (VEGFR)-tyrosine kinase inhibitor (TKI) treatment. SECONDARY OBJECTIVES: I. To compare the progression-free survival and proportion who experience an objective response (defined as complete clinical response \[cCR\] + partial response \[PR\]) in patients with advanced renal cell carcinoma receiving bevacizumab plus everolimus and everolimus alone. II. To compare grade 3 or higher toxicity in patients receiving each treatment regimen. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive everolimus orally (PO) once daily (QD) on days 1-28. ARM II: Patients receive everolimus PO QD on days 1-28 and bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 8 weeks until disease progression and then every 6 months for up to 5.5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
77
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
Fowler Family Center for Cancer Care
Jonesboro, Arkansas, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Kaiser Permanente-Anaheim
Anaheim, California, United States
Kaiser Permanente-Deer Valley Medical Center
Antioch, California, United States
Overall Survival (OS)
Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Time frame: The time from date of randomization to date of death due to any cause, assessed up to 5.5 years
Progression-free Survival (PFS)
Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Time frame: The time from randomization to disease progression or death from any cause, assessed up to 5.5 years
Objective Response Rate (CR + PR)
The response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients.
Time frame: Up to 5.5 years
Toxicities, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
The number of patients reporting grade 3 or higher adverse events as graded by the NCI's Common Toxicity Criteria (CTCAE) Version 4 are reported here. A complete list of all reported adverse events is reported in the Adverse Events section of this report.
Time frame: Up to 30 days after completion of study treatment
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