Immediate Versus Deferred Cytoreductive Nephrectomy With Ipilimumab/Nivolumab in mRCC

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

172 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-01

Study Completion Date

2029-02-01

Brief Summary

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The goal of this clinical trial is to learn whether the timing of surgery (cytoreductive nephrectomy) improves outcomes when combined with immunotherapy (ipilimumab and nivolumab) in adults with metastatic clear cell renal cell carcinoma.

The main questions this study aims to answer are:

* Does upfront (immediate) surgery before immunotherapy improve survival compared to delayed surgery after immunotherapy?
* What medical problems (side effects or complications) occur with each treatment sequence?
* How do the two strategies affect quality of life?

Researchers will compare two groups:

* Upfront surgery group: Participants will have surgery first, then receive 4 cycles of ipilimumab/nivolumab, followed by nivolumab maintenance.
* Deferred surgery group: Participants will receive 4 cycles of ipilimumab/nivolumab first, then surgery, followed by nivolumab maintenance.

Participants will:

* Be randomly assigned to one of the two groups
* Undergo regular clinic visits, imaging tests, and blood collections for safety and biomarker studies
* Be followed for 15 months to check disease progression, complications, survival, and quality of life

This trial will help determine the best timing for surgery in the era of immunotherapy and provide evidence for improved treatment strategies for patients with metastatic kidney cancer

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Detailed Description

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This is a multicenter, randomized, open-label phase III trial designed to evaluate the optimal timing of cytoreductive nephrectomy (CN) in patients with synchronous metastatic clear cell renal cell carcinoma (mRCC) in the era of immune checkpoint inhibitors.

Although CN has historically been considered standard in mRCC, the timing of surgery (immediate vs deferred) remains controversial, particularly after the introduction of immune checkpoint blockade. Recent retrospective studies and meta-analyses suggest potential survival benefits of deferred CN following systemic therapy, but high-level prospective evidence is lacking.

In this study, participants with intermediate or poor IMDC risk mRCC will be randomized into two groups:

* Upfront CN arm: Patients undergo immediate CN followed by 4 cycles of ipilimumab plus nivolumab (Ipi/Nivo) and then nivolumab maintenance.
* Deferred CN arm: Patients receive 4 cycles of Ipi/Nivo induction first, followed by CN, and then nivolumab maintenance.

The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS), perioperative morbidity, radiologic response, rate of unresectable tumors in the deferred group, impact of CN on early progression, surgical outcomes, and quality of life. Exploratory endpoints include biomarker studies using peripheral blood mononuclear cells (PBMCs) to characterize responders vs non-responders to Ipi/Nivo.

Patients will be followed for 15 months after treatment initiation, with regular imaging, clinical assessments, and laboratory monitoring. Approximately 172 patients across 12 institutions in Korea will be enrolled.

The results of this trial are expected to establish high-level evidence regarding the role and optimal timing of CN in mRCC, improve clinical decision-making, and provide guidance for treatment strategies in the immuno-oncology era

Conditions

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Metastatic Renal Cell Carcinoma ( mRCC)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Upfront Cytoreductive Nephrectomy (CN)

Participants will undergo immediate cytoreductive nephrectomy. About 4 weeks after surgery, they will receive induction therapy with ipilimumab plus nivolumab for 4 cycles, followed by maintenance nivolumab. Regular assessments of progression, perioperative complications, safety, and quality of life will be performed for 15 months.

Group Type EXPERIMENTAL

Ipilimumab plus Nivolumab

Intervention Type DRUG

Participants will receive 4 cycles of ipilimumab combined with nivolumab as induction therapy, followed by nivolumab maintenance depending on randomization schedule (before or after surgery).

Cytoreductive Nephrectomy

Intervention Type PROCEDURE

Surgical removal of the primary kidney tumor (cytoreductive nephrectomy), performed either upfront (before systemic therapy) or deferred (after 4 cycles of ipilimumab/nivolumab induction), depending on randomization arm.

Deferred Cytoreductive Nephrectomy (CN)

Participants will first receive 4 cycles of ipilimumab plus nivolumab induction therapy. After reassessment, they will undergo deferred cytoreductive nephrectomy, followed by maintenance nivolumab. Safety, perioperative complications, progression, and quality of life will be evaluated regularly for 15 months

Group Type EXPERIMENTAL

Ipilimumab plus Nivolumab

Intervention Type DRUG

Participants will receive 4 cycles of ipilimumab combined with nivolumab as induction therapy, followed by nivolumab maintenance depending on randomization schedule (before or after surgery).

Cytoreductive Nephrectomy

Intervention Type PROCEDURE

Surgical removal of the primary kidney tumor (cytoreductive nephrectomy), performed either upfront (before systemic therapy) or deferred (after 4 cycles of ipilimumab/nivolumab induction), depending on randomization arm.

Interventions

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Ipilimumab plus Nivolumab

Participants will receive 4 cycles of ipilimumab combined with nivolumab as induction therapy, followed by nivolumab maintenance depending on randomization schedule (before or after surgery).

Intervention Type DRUG

Cytoreductive Nephrectomy

Surgical removal of the primary kidney tumor (cytoreductive nephrectomy), performed either upfront (before systemic therapy) or deferred (after 4 cycles of ipilimumab/nivolumab induction), depending on randomization arm.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Participants must meet all of the following:
* Age ≥ 19 years (male or female).
* Histologically confirmed synchronous metastatic clear cell renal cell carcinoma.
* ECOG performance status 0-1.
* At least one measurable metastatic lesion (per RECIST v1.1).
* Primary renal tumor considered surgically resectable.
* IMDC intermediate- or poor-risk classification.
* Estimated life expectancy \> 3 months.
* Ability to understand and voluntarily sign informed consent.

Exclusion Criteria

* Prior systemic therapy for metastatic RCC.
* History of another malignancy diagnosed or treated within 2 years (except for cured non-melanoma skin cancer or in-situ cancers).
* Significant comorbid conditions making participation inappropriate, such as:

Moderate to severe cardiovascular, cerebrovascular, pulmonary, or hepatic disease.

* History or suspicion of autoimmune disease incompatible with immune checkpoint inhibitor therapy.
* Requirement for systemic corticosteroid therapy \>10 mg/day prednisone equivalent, or other immunosuppressive drugs.
* Any other condition judged by the investigator to make the patient unsuitable for trial participation.

Minimum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No