Primary Tumor Ablation and Outcome in Metastatic Renal Cell Carcinoma Treated With Immunotherapy Combinations.

This is Phase IV, randomized, multi arm, multicenter, low interventional clinical trial, aiming to evaluate if treatment of primary tumor in mRCC patients with initial benefit to anti-PD1- based therapy (SOC) can improve the overall survival. All patients eligible according to inclusion and exclusion criteria will be enrolled and randomized to different treatment options based on tumor extension of the primary kidney cancer. Those with primary kidney cancer ≤ 4 cm will be randomized 1:1:1 to receive: * Cytoreductive Nephrectomy + standard of care (SOC) or * RT on primary tumor + SOC or SOC alone. Those with primary kidney cancer \> 4 cm will be randomized 1:1 to receive: • Deferred Cytoreductive Nephrectomy + SOC or SOC alone. Patients randomized to Deferred Cytoreductive Nephrectomy can be treated with one among radical nephrectomy; partial nephrectomy or lumpectomy. Patients randomized to RT should be treated with single shot of 25 Gy (or with multiple fractions with equivalent biological dose). The SOC medical therapy is the continuation of the combination of medical therapy for mRCC including one of the available combination among axitinib + pembrolizumab or cabozantinib + nivolumab or lenvatinib + pembrolizumab or nivolumab alone after nivolumab + ipilimumab.

NCT Number	NCT06903312
Lead Sponsor	Fondazione Policlinico Universitario Agostino Gemelli IRCCS Collaborators: Associazione Italiana per la Ricerca sul Cancro
Conditions	Renal Cell Cancer, Kidney Neoplasm, Immunotherapy, Kidney Cancer, Surgery Programmed, Radiotherapy
Enrollment	409 participants
Start Date	2025-06-15
Primary Completion	2027-10-01 (estimated)
Study Completion	2028-04-01 (estimated)
Updated on ClinicalTrials.gov	2025-07-03