Deferred Cytoreductive Nephrectomy in Synchronous Metastatic Renal Cell Carcinoma: The NORDIC-SUN-Trial — NORDIC-SUN  

Kidney Cancer Clinical Trial

Official title: Multicenter Randomized Trial of Deferred Cytoreductive Nephrectomy in Synchronous Metastatic Renal Cell Carcinoma Receiving Checkpoint Inhibitors: a DaRenCa and NoRenCa Trial Evaluating the Impact of Surgery or No Surgery. The NORDIC-SUN-Trial

Status Recruiting

Clinical Trial Summary

BACKGROUND: For synchronous metastatic renal cell carcinoma (RCC), surgical resection of the primary tumor in the presence of distant metastases has been the standard of therapy for select patients followed by systemic therapy. In the era of TKIs two randomized trials, CARMENA and SURTIME, have questioned the role and timing of surgery in these patients, results point towards no surgery or a deferred approach. RATIONALE: The antitumor activity of immune checkpoint blockage (ICB) is more potent than other therapy in mRCC. The deferred cytoreductive nephrectomy approach ensures systemic therapy for all patients, avoid systemic treatment delay, and spare surgery in patients with progressive tumors. Current data only point towards a survival benefit for cytoreductive nephrectomy in intermediate risk patients, but not in poor risk patients HYPOTHESIS: Deferred cytoreductive nephrectomy after initial nivolumab combined with ipilimumab or a TKI/IO-combination will improve OS in patients with synchronous metastatic RCC and ≤3 IMDC risk features This is an open, randomized, multicenter comparison trial, designed to evaluate the effect of deferred cytoreductive nephrectomy compared with no surgery following initial nivolumab combined with ipilimumab or a TKI-combination, in mRCC patients with IMDC intermediate and poor risk.

Clinical Trial Description

OUTLINE: This is a multicenter trial, patients are stratified according to institution, treatment choice, number of IMDC risk factors, and combined elevated neutrophil-lymphocyte ratio and hyponatremia. All patients will receive induction checkpoint immunotherapy immediately after inclusion. After 3 months or a total of 4 series of nivolumab combined with ipilimumab or a TKI/IO-combination, the patient will be discussed for resectability at the multidisciplinary meeting (MDT). Whether the patient is eligible for cytoreductive nephrectomy is at the discretion of the urologist at the local MDT. Patients with ≤ 3 IMDC risk factors and deemed suitable for cytoreductive nephrectomy will then undergo randomization. Patients deemed not suitable for surgery or have > 3 IMDC risk features at the 3 month evaluation continue systemic therapy for 3 months, followed by a 2nd evaluation. Patients with ≤ 3 IMDC risk factors and deemed suitable for cytoreductive nephrectomy at 2nd evaluation will then undergo randomization. Patients deemed not suitable for surgery or have > 3 IMDC risk features at the 6 month evaluation continue systemic therapy. Nivolumab may continue until unacceptable toxicity or total treatment length of 2 years from inclusion. ARM A: Deferred cytoreductive nephrectomy, followed by maintenance nivolumab or a TKI/IO-combination. ARM B: No surgery, receive maintenance nivolumab or a TKI/IO-combination. Patients undergo tumor tissue, blood, and stool collection at baseline, 3 and 6 months, for planned translational research. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Kidney Cancer
• Kidney Neoplasms
• Renal Cell Carcinoma Metastatic
• Synchronous Neoplasm

• NCT number: NCT03977571
• Study type: Interventional
• Source: University of Aarhus
• Contact: Niels Fristrup, MD PhD
• Phone: 004520914161
• Email: niels.fristrup@rm.dk
• Status: Recruiting
• Phase: N/A
• Start date: July 6, 2020
• Completion date: September 1, 2028