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.
Informed consent obtained before any study-specific procedures. Patients must be able to understand and be willing to sign a written informed consent.
Male or female patient ≥18 years of age.
Histological or cytological documentation of renal cell carcinoma with predominantly clear cell histology.
Evidence of primary renal cancer.
More than one treatment for metastatic or locally advanced renal cell carcinoma.
Solitary kidney
Any contraindication to surgery or radiotherapy on primary renal tumor.
Discontinuation (definitive) of one of the therapies for mRCC due to toxicity (previous discontinuation of ipilimumab in the ipilimumab + nivolumab combo is allowed).
Parallel
Deferred Cytoreductive Nephrectomy + medical treatment
Procedure/SurgeryPatients 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.
Radiotherapy + medical treatment
RadiationPatients 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.
Medical therapy
DrugMedical 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.
30-months Overall Survival for surgery vs. control
The primary endpoint of the study is to assess the difference in 30-months overall survival (OS) between patients who receive or not the deferred citoreductive nephrectomy (CN) while on therapy with SOC for mRCC.
Median overall survival for surgery vs. control
To assess the difference in overall survival (OS) between patients who receive or not the deferred citoreductive nephrectomy (CN) while on therapy with SOC for mRCC from the beginning of the anti-PD1-based therapy.
Median Progression Free Survival for surgery vs. control
To assess the difference in progression-free survival (PFS) between patients who receive or not the deferred citoreductive nephrectomy (CN) while on therapy with SOC for mRCC.
Median Overall Survival for radiotherapy vs. control
To assess the difference in overall survival (OS) between patients who receive or not the radiotherapy on primary tumor while on therapy with SOC for mRCC among those with primary tumor up to 4 cm at randomization.
Median Progression Free Survival for radiotherapy vs. control
To assess the difference in progression-free survival (PFS) between patients who receive or not the radiotherapy on primary tumor while on therapy with SOC for mRCC among those with primary tumor up to 4 cm at randomization.
Difference in the proteomic profile
The study aims also to describe the change of proteome after surgery or radiotherapy on primary tumor compared to the baseline and to evaluate if specific proteome profiles at baseline are related to different outcomes. A blood tumor sample will be performed at the time of randomization for all patients and after eight weeks from CN or the end of RT to assess the proteomic profile.
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Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Lead sponsor
AIRC (Italian Association for Cancer Research)
Collaborator
