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

NCT06903312 | Recruiting Phase 4

• 1 other identifier: 7056
• Study Type: interventional
• Target: 409
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

renal cancer; primary tumor; cytoreductive nephrectomy; immunothreapy; radiotherapy

Outcome Measures

Primary Outcomes (1)

• 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.

  30 months

Secondary Outcomes (8)

• Median overall survival for surgery vs. control

  30 months

• Median Progression Free Survival for surgery vs. control

  30 months

• Median Overall Survival for radiotherapy vs. control

  30 months

• Median Progression Free Survival for radiotherapy vs. control

  30 months

• Incidence of adverse events

  30 months

Other Outcomes (1)

• Difference in the proteomic profile

  Before and 8 weeks after surgery or radiotherapy.

Study Arms (3)

Radiotherapy

EXPERIMENTAL

Patients with tumors up to 4 cm can receive RT single shot of 25 Gy (or with multiple fractions with equivalent biological dose).

Radiation: Radiotherapy + medical treatment

Deferred Cytoreductive Nephrectomy

EXPERIMENTAL

Patients randomized to Deferred Cytoreductive Nephrectomy can be treated with one among radical nephrectomy; partial nephrectomy or lumpectomy.

Procedure: Deferred Cytoreductive Nephrectomy + medical treatment

Control

ACTIVE COMPARATOR

patients in the control arm continue to receive immuno-based medical treatment for mRCC.

Drug: Medical therapy

Interventions

Deferred Cytoreductive Nephrectomy + medical treatment PROCEDURE

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.

Deferred Cytoreductive Nephrectomy

Radiotherapy + medical treatment RADIATION

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.

Radiotherapy

Medical therapy DRUG

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.

Also known as: Standard of Care (SOC)

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Measurable or not measurable metastatic disease according to Response Evaluation Criteria in Solid Tumors criteria, version 1.1 \[22\].
• Eastern Cooperative Oncology Group performance status of ≤1.
• Life expectancy of at least 9 months.
• Under treatment with one anti-PD1 based therapy (SOC) among axitinib + pembrolizumab or cabozantinib + nivolumab or lenvatinib + pembrolizumab or nivolumab alone after nivolumab + ipilimumab for at least 24 but not more than 52 weeks at the time of the signed informed consent and without evidence of progressive disease based on RECIST criteria v 1.1 \[21\].
• Eligible to continue the combination of therapies for mRCC (or nivolumab alone in case of nivolumab + ipilimumab).
• Women of childbearing potential and men must agree to use adequate contraception since signing of the informed consent form until at least 3 months after the last study drug administration. The investigator or a designated associate is requested to advise the subject how to achieve an adequate birth control. Adequate contraception is defined in the study as any medically recommend method (or combination of methods) as per standard of care.
• Adequate bone-marrow, liver, and renal function as assessed by the following laboratory requirements conducted within 7 days of starting to study treatment:
• Creatinine value \<2.5 mg/dl and creatinine clearance \> 30 ml/min evaluated by the Cockcroft-Gault Formula.
• Total bilirubin ≤1∙5 × the upper limit of normal (ULN);
• Alanine aminotransferase and aspartate aminotransferase ≤2 × ULN (≤5 × ULN for patients with liver involvement of their cancer);
• International normalized ratio (INR) and partial thromboplastin time (PTT) ≤1∙5 × ULN. Subjects who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate if no prior evidence of an underlying abnormality in coagulation parameters exists. Close monitoring of at least weekly evaluations will be performed until INR and PTT are stable based on a pre-dose measurement as defined by the local standard of care;

You may not qualify if:

• 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).
• Concurrent or previous cancer within 3 years before enrolment EXCEPT curatively treated cervical cancer in situ, non-melanoma skin cancer and pT2 prostate cancer with PSA\<0.01 or non-muscle invasive bladder cancer.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before the signed informed consent.
• Pregnancy or breast-feeding. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before surgery or radiotherapy on primary tumor, and a negative result must be documented before start of treatment.
• Any cardiological condition among:
• Congestive heart failure of New York Heart Association class 3 or worse.
• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before start of study drug.
• Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted).
• Uncontrolled hypertension (systolic blood pressure \>150 mmHg or diastolic pressure \>90 mmHg despite optimal medical management).
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), pulmonary embolism within the 4 months before start of study.
• Ongoing infection higher than National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 6.0 grade 2.
• Known history of human immunodeficiency (HIV) virus infection or known history of chronic hepatitis B or C.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead
• AIRC (Italian Association for Cancer Research): collaborator

Study Sites (1)

Fondazione Policlinico Universitario A. Gemelli IRCCS

Roma, 00168, Italy

RECRUITING

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

Radiotherapy; Nutrition Therapy; Standard of Care

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Roberto Iacovelli, M.D.; Ph.D.

  Catholic University of Rome, Italy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Roberto Iacovelli, M.D.; Ph.D.

CONTACT

+390630157373; roberto.iacovelli@policlinicogemelli.it

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be valuated for local therapy (ie: surgery or radiotherapy) while they are receiving immunotherapy-based therapy.

Study Record Dates

• First Submitted: March 24, 2025
• First Posted: March 30, 2025
• Study Start: June 15, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: July 3, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)