This phase III trial compares nephrectomy (surgery to remove a kidney or part of a kidney) with nivolumab to the usual approach of nephrectomy followed by standard post-operative follow-up and monitoring, in treating patients with kidney cancer that is limited to a certain part of the body (localized). Nivolumab is a drug that may help stimulate the immune system to attack any cancer cells that may remain after surgery. The addition of nivolumab to the usual surgery could prevent the cancer from returning. It is not yet known whether nivolumab and nephrectomy is more effective than nephrectomy alone in treating patients with kidney cancer.
PRIMARY OBJECTIVE: I. To compare recurrence-free survival (RFS) between patients with renal cell carcinoma randomly assigned to perioperative nivolumab in conjunction with radical or partial nephrectomy with patients randomized to surgery alone. SECONDARY OBJECTIVES: I. To evaluate for differences in recurrence-free survival associated with perioperative nivolumab compared to surgery alone among the subset of patients with clear cell histology. II. To compare the overall survival between the two arms. III. To describe the safety and tolerability of perioperative nivolumab. CORRELATIVE OBJECTIVES: I. To correlate the primary tumor's expression of PD-L1 with outcome. II. To correlate the expression of PD-L1 on tumor tissue at nephrectomy and recurrence with outcome. III. To archive images for potential central confirmation of recurrence and for future correlative work with American College of Radiology Imaging Network (ACRIN), including markers predicting outcome or response. IV. To prospectively collect tumor and biologic specimens (e.g., serum, peripheral blood mononuclear cells \[PBMCs\]) for future correlative studies. V. To characterize the pharmacokinetics of nivolumab and explore exposure response relationships with respect to safety and efficacy. VI. To characterize the immunogenicity of nivolumab. QUALITY OF LIFE OBJECTIVE: I. To evaluate differences in change from baseline in patient-reported symptoms and toxicities among patients randomized to treatment with nivolumab compared to surgery alone. OTHER EXPLORATORY OBJECTIVES: I. To explore descriptively the efficacy of treatment with nivolumab in patients with non-clear cell (including unclassified) histologies. II. To characterize the effects of nivolumab on bone metabolism and bone density. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 14 days for 2 cycles. Patients then undergo partial or radical nephrectomy 7-28 days later. Patient then receive nivolumab over 30 IV on day 1. Treatment repeats every 14 days for 6 cycles, and then every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients enrolled after Amendment 4 receive nivolumab IV over 30 minutes on day 1. Patients then undergo partial or radical nephrectomy 7-28 days later. Patients then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 9 cycles in the absence of disease progression or unacceptable toxicity. ARM B: Patients undergo partial or radical nephrectomy within 8 weeks after registration followed by observation. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and every 12 months for 5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
819
Undergo nephrectomy
Given IV
Undergo observation
Ancillary studies
Ancillary studies
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
Veterans Administration Medical Center - Birmingham
Birmingham, Alabama, United States
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
Cancer Center at Saint Joseph's
Phoenix, Arizona, United States
Banner University Medical Center - Tucson
Tucson, Arizona, United States
Recurrence-free Survival (RFS) Rate at 5 Years
RFS is defined as time from randomization to disease recurrence or death from any cause. Patients who did not undergo nephrectomy or were not disease-free following nephrectomy were considered as having an event at day 1. Patients that are alive without an event were censored at the date of last disease evaluation. RFS rate at 5 years was the proportion of patients who are recurrence-free and alive at 5 years based on Kaplan-Meier estimates.
Time frame: Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 3 years
Recurrence-free Survival (RFS) Rate at 3 Years Among Patients With Clear Cell Histology
RFS is defined as time from randomization to disease recurrence or death from any cause. Patients who did not undergo nephrectomy or were not disease-free following nephrectomy were considered as having an event at day 1. Patients that are alive without an event were censored at the date of last disease evaluation. RFS rate at 3 years was the proportion of patients who are recurrence-free and alive at 3 years based on Kaplan-Meier estimates.
Time frame: Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 1 year
Overall Survival Rate at 5 Years
Overall survival is defined as time from randomization to death from any cause. Overall survival rate at 5 years was the proportion of patients who are alive at 5 years based on Kaplan-Meier estimates.
Time frame: Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 3 years
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University of Arizona Cancer Center-North Campus
Tucson, Arizona, United States
Kaiser Permanente-Anaheim
Anaheim, California, United States
Sutter Auburn Faith Hospital
Auburn, California, United States
AIS Cancer Center at San Joaquin Community Hospital
Bakersfield, California, United States
Kaiser Permanente-Baldwin Park
Baldwin Park, California, United States
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