Ignite Creation Date:
2025-12-24 @ 5:58 PM
Ignite Modification Date:
2025-12-26 @ 2:05 PM
Study NCT ID:
NCT07233668
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-12-03
First Post:
2025-09-03
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Immediate Versus Deferred Cytoreductive Nephrectomy With Ipilimumab/Nivolumab in mRCC
Sponsor:
Seoul National University Hospital
Organization:
Study Overview
Official Title:
Immediate Versus Deferred Cytoreductive Nephrectomy With Ipilimumab/Nivolumab in Metastatic Clear Cell Renal Cell Carcinoma: A Multicenter, Randomized, Open-Label, Phase III Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2025-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
IVE in mRCC
Brief Summary:
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
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
Detailed Description:
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
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
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: