This phase III trial compares the effect of adding surgery to a standard of care immunotherapy-based drug combination versus a standard of care immunotherapy-based drug combination alone in treating patients with kidney cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, pembrolizumab, and avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Surgery to remove the kidney, called a nephrectomy, is also considered standard of care; however, doctors who treat kidney cancer do not agree on its benefits. It is not yet known if the addition of surgery to an immunotherapy-based drug combination works better than an immunotherapy-based drug combination alone in treating patients with kidney cancer.
STEP 1 REGISTRATION: Participants must have a histologically proven diagnosis of clear cell or non-clear cell renal cell carcinoma. Participants with collecting duct carcinoma histology are not eligible. Participants with multifocal or bilateral tumors are eligible
STEP 1 REGISTRATION: Participants must have primary tumor in place
Computed tomography (CT) scan of the chest (can be performed without contrast if CT contrast cannot be given)
CT of abdomen and pelvis with contrast OR magnetic resonance imaging (MRI) of the abdomen and pelvis with or without contrast
STEP 1 REGISTRATION: Participants must not have known active brain metastases. Participants with previously treated brain metastases are eligible if participant has no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies are not required. If brain imaging studies are performed, they must be negative for disease
Treatment naive participants must not have received any prior lines of systemic therapy for metastatic renal cell carcinoma beyond the line intended as part of protocol therapy
Previously treated participants must not have received any systemic therapy for metastatic renal cell carcinoma beyond the one regimen received off protocol as specified in Step 1 pre-randomization treatment
Treatment naive participants must not have received any pre-randomization treatment.
Parallel
Cytoreductive Nephrectomy
Procedure/SurgeryRadical or partial nephrectomy may be performed using laparoscopic, open, or robotic approaches. Surgery should be performed within 8 weeks of randomization
Active Comparator
DrugNivolumab 240 mg IV 1 q 2 weeks OR Nivolumab 480 mg IV 1 q 4 weeks OR Pembrolizumab 200 mg IV 1 q 3 weeks Axitinib 5 mg oral Daily BID OR Avelumab 10 mg/kg IV 1 q 2 weeks Axitinib 5 mg oral Daily BID
Overall survival
Analysis will be intent-to-treat. Evidence suggesting early termination of the trial and a conclusion that the cytoreductive nephrectomy (CN) approach is superior to treatment alone would be if the null hypothesis is rejected at the one-sided 0.005 level. For the second and third interim analyses, the null and alternative hypotheses with respect to survival will be tested, with superiority tested at the one-sided 0.005 level, and futility determined to be met if the (CN versus no CN) hazard ratio is greater than or equal to 1. A proportional hazards model will be fit to estimate the hazard ratio adjusting for the stratification factors as covariates in the model. Will evaluate whether each of the stratification factors are predictive factors of cytoreductive nephrectomy by placing an interaction term corresponding to each stratification factor and treatment arm in the proportional hazards survival model.
Overall survival in subset who received assigned protocol treatment
Will be included in the proportional hazards regression model adjusting for stratification factors as covariates.
Progression-free survival
A proportional hazards model will be used to compare progression-free survival between arms, adjusting for the stratification factors as covariates.
Objective response
Objective response includes all confirmed and unconfirmed partial and complete responses. Baseline will be disease assessment at randomization. Response Evaluation Criteria in Solid Tumors response rates will be evaluated, excluding the primary tumor in the kidney because that disease will be removed in half the participant's post-randomization. Comparison of response rates will be performed using logistic regression with stratification factors as covariates and an indicator for treatment arm.
Change in maximum diameter of primary tumor
Descriptive statistics will be provided including stratified results by treatment regimen received. Potential additional analyses may include assessment of the interaction between change in primary tumor and randomized treatment arm. This will be modeled as an interaction term in the proportional hazards survival model.
Click on the lead sponsor to view all of their trials.
SWOG Cancer Research Network
Lead sponsor
National Cancer Institute (NCI)
Collaborator
