NCT04510597

Comparing the Outcome of Immunotherapy-Based Drug Combination Therapy With or Without Surgery to Remove the Kidney in Metastatic Kidney Cancer, the PROBE Trial

Phase III Trial of Immunotherapy-Based Combination Therapy With or Without Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma (PROBE Trial)

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 364 (estimated)
• Sponsor: SWOG Cancer Research Network · Network
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

PRIMARY OBJECTIVE: I. To compare overall survival in participants with newly diagnosed metastatic renal cell carcinoma who are randomized to receive immune checkpoint inhibitor-based combination treatment plus cytoreductive nephrectomy versus immune checkpoint inhibitor-based combination treatment alone. SECONDARY OBJECTIVES: I. To compare overall survival between arms in the subset who received their assigned protocol treatment. II. To assess complications of nephrectomy and post-randomization drug toxicities. III. To compare objective response rate in metastatic sites between the arms in participants with measurable metastatic disease. IV. To assess change in diameter of primary tumor at week 12 disease assessment in participants who have received pre-randomization treatment. BANKING OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: PRE-RANDOMIZATION TREATMENT: Treatment naive patients are assigned to 1 of 3 treatment regimens per standard of care. REGIMEN I: Patients receive nivolumab intravenously (IV) and ipilimumab IV. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV on day 1. Cycles repeat every 2-4 weeks in the absence of disease progression or unacceptable toxicity. REGIMEN II: Patients receive pembrolizumab IV on day 1 and axitinib orally (PO) twice daily (BID) on days 1-21. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. REGIMEN III: Patients receive avelumab IV on day 1 and axitinib PO BID on days 1-14. Cycles repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. NOTE: Some patients may have already completed the standard of care pre-randomization treatment specified above off-trial. RANDOMIZATION TREATMENT: Between 10-14 weeks from the start of on-trial or off-trial pre-randomization treatment, patients are randomized to 1 of 2 arms. ARM I: Patients receive nivolumab IV, pembrolizumab IV, or avelumab IV on day 1. Patients also receive axitinib PO BID. Cycles with nivolumab repeat every 2 or 4 weeks, cycles with pembrolizumab repeat every 3 weeks, and cycles with avelumab repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. ARM II: Within 42 days following randomization, patients undergo radical or partial nephrectomy in addition to nivolumab, pembrolizumab, avelumab, and axitinib as in Arm I in the absence of disease progression or unacceptable toxicity. Axitinib should be stopped at least 24 hours prior to surgery. After completion of trial treatment, patients are followed up every 3 months for the first year, every 6 months for years 2 and 3, and then annually for up to 7 years from randomization.

Conditions

• Metastatic Clear Cell Renal Cell Carcinoma
• Metastatic Renal Cell Carcinoma
• Stage IV Renal Cell Cancer AJCC v8

Interventions

Type	Name	Description
PROCEDURE	Cytoreductive Nephrectomy	Radical or partial nephrectomy may be performed using laparoscopic, open, or robotic approaches. Surgery should be performed within 8 weeks of randomization
DRUG	Active Comparator	Nivolumab 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

Timeline

• Start date: 2021-03-08
• Primary completion: 2033-07-01
• Completion: 2033-07-01
• First posted: 2020-08-12
• Last updated: 2025-09-09

Locations

387 sites across 1 country: United States

Regulatory

• FDA-regulated drug study