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.

Conditions

• Renal Cell Cancer
• Kidney Neoplasm
• Immunotherapy
• Kidney Cancer
• Surgery Programmed
• Radiotherapy

Interventions

PROCEDURE

Deferred Cytoreductive Nephrectomy + medical treatment

Patients randomized to Deferred Cytoreductive Nephrectomy can be treated with one among radical nephrectomy; partial nephrectomy or lumpectomy. Patients will continue to receive the ongoing medical treatment before the randomization.

RADIATION

Radiotherapy + medical treatment

Patients randomized to RT should be treated with single shot of 25 Gy (or with multiple fractions with equivalent biological dose). Patients will continue to receive the ongoing medical treatment before the randomization.

DRUG

Medical therapy

Medical therapy is the continuation of the immune-based combo for mRCC including one of the available options among axitinib + pembrolizumab or cabozantinib + nivolumab or lenvatinib + pembrolizumab or nivolumab alone after nivolumab + ipilimumab.

Sponsors & Collaborators

• AIRC (Italian Association for Cancer Research)

  collaborator UNKNOWN

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS

  lead OTHER

Principal Investigators

• Roberto Iacovelli, M.D.; Ph.D. · Catholic University of Rome, Italy

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-06-15

Primary Completion

2027-10-01

Completion

2028-04-01

Countries

• Italy

Study Locations