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

Summary

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.

Timeline

Start

2025-06-15

Primary completion

2027-10-01

Completion

2028-04-01

Publications

• Iacovelli R, Ciccarese C, Arduini D, Tagliaferri L, Minervini A, Simone G, Ficarra V, Porta C, Calabro F, Zucali P, Troisi P, Francolini G, Morganti AG, Franzese C, Jereczek-Fossa BA, Maria Rocco BC. The ITALIC-RCC: A Randomized Trial on Clinical and Humoral Impact of Primary Tumor Ablation by Surgery or Radiotherapy in Metastatic Renal Cell Carcinoma Treated with Checkpoint Inhibitors. Eur Urol Open Sci. 2026 Jul 3;90:77-83. doi: 10.1016/j.euros.2026.06.004. eCollection 2026 Aug.

Drugs

Indications