Metastatic Renal Cell Carcinoma ( mRCC)IVE in mRCCNCT07233668
Immediate Versus Deferred Cytoreductive Nephrectomy With Ipilimumab/Nivolumab in mRCC
A study testing Ipilimumab plus Nivolumab and Cytoreductive Nephrectomy in people with Metastatic Renal Cell Carcinoma ( mRCC), run by Seoul National University Hospital.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Metastatic Renal Cell Carcinoma ( mRCC)
- What is being tested?
- Ipilimumab plus Nivolumab and Cytoreductive Nephrectomy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 172 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2025to 1 Feb 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 9Show fewer
- IMDC intermediate- or poor-risk classification.
- Estimated life expectancy > 3 months.
- Ability to understand and voluntarily sign informed consent.
Who cannot join
- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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
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:
Read more
- 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
Read the 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
- Conditions
- Metastatic Renal Cell Carcinoma ( mRCC)
- Being tested
- Ipilimumab plus Nivolumab, Cytoreductive Nephrectomy
- Keywords
- Metastatic Renal Cell Carcinoma, Immune Checkpoint Inhibitor, Cytoreductive Nephrectomy, Progression-Free Survival, Randomized Clinical Trial
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ipilimumab plus NivolumabDrug
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 NephrectomyProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Upfront Cytoreductive Nephrectomy (CN) | Experimental | 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. Receives: Drug: Ipilimumab plus Nivolumab; Procedure: Cytoreductive Nephrectomy |
| Deferred Cytoreductive Nephrectomy (CN) | Experimental | 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 Receives: Drug: Ipilimumab plus Nivolumab; Procedure: Cytoreductive Nephrectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS) assessed by RECIST version 1.1
Time from randomization to first documented disease progression or death from any cause, whichever occurs first. Disease progression will be assessed according to RECIST version 1.1 criteria and clinical evaluation.
Measured: Up to 15 months after treatment initiation
Secondary outcomes (11)
Overall Survival (OS)
Time from randomization to death from any cause.
Measured: Up to 15 months after treatment initiation
Rate and Severity of Perioperative Complications Assessed by Clavien-Dindo Classification
Proportion of patients experiencing perioperative complications graded using the Clavien-Dindo classification (Grades I-V).
Measured: Within 90 days after cytoreductive nephrectomy
Rate and Severity of Perioperative Adverse Events Assessed by CTCAE v4.0
Severity of postoperative adverse events graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Grade 1-5).
Measured: Within 90 days after cytoreductive nephrectomy
Radiologic Tumor Response Rate Assessed by RECIST v1.1
Rate of complete response (CR) and partial response (PR) to ipilimumab/nivolumab, assessed using RECIST version 1.1.
Measured: At baseline, at 12 weeks (after 4 cycles of ipilimumab/nivolumab induction therapy), and every 12 weeks thereafter up to 15 months
Rate of Unresectable Tumors in the Deferred Arm
Proportion of participants in the deferred arm with tumors deemed unresectable at surgery.
Measured: At the time of planned deferred cytoreductive nephrectomy
Early Disease Progression Rate Within 4 Weeks Post-Nephrectomy
Proportion of patients showing disease progression (PD) within 4 weeks after surgery in both arms.
Measured: Within 4 weeks of cytoreductive nephrectomy
Rate of Open vs Minimally Invasive Surgical Approach
Proportion of surgeries performed using open or minimally invasive techniques.
Measured: At time of cytoreductive nephrectomy
Extent of Surgery (e.g., Radical vs Partial Nephrectomy; Lymphadenectomy Yes/No)
Surgical extent categories documented at time of surgery.
Measured: At time of cytoreductive nephrectomy
Quality of Life Assessed by FACT-Kidney Symptom Index 15-item (FKSI-15)
Quality of life measured using the Functional Assessment of Cancer Therapy - Kidney Symptom Index 15-item (FKSI-15) questionnaire.
The total score ranges from 0 to 60, with higher scores indicating better quality of life and fewer kidney cancer-related symptoms.
Measured: Baseline, at 12 weeks (after 4 cycles of therapy), and every 12 weeks thereafter up to 15 months
Quality of Life Assessed by EORTC QLQ-C30
Patient-reported outcomes evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Scores for each domain range from 0 to 100.
Measured: Baseline, at 12 weeks (after 4 cycles of therapy), and every 12 weeks thereafter up to 15 months
Health Utility Score Assessed by EQ-5D-5L
Health status measured using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire.
The EQ-5D-5L utility index score typically ranges from <0 (health states worse than death) to 1 (full health), with higher scores representing better overall health status.
The EQ-VAS records self-rated health on a 0-100 scale, where higher scores indicate better perceived health.
Measured: Baseline, at 12 weeks (after 4 cycles of therapy), and every 12 weeks thereafter up to 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2025
- Study start1 Dec 2025 (estimated)
- Primary completion1 Oct 2028 (estimated)
- Study completion1 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Metastatic Renal Cell Carcinoma ( mRCC)Studies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 172 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chang Wook Jeong, Seoul National University Hospital
- Investigators
- Chang Wook Jeong, MD, PhD, Principal investigator, Seoul National Universtiy Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07233668
- Sponsor's protocol ID
- 2502-014-1611
- Acronym
- IVE in mRCC
- Status last verified
- Nov 2025
- First submitted
- 3 Sep 2025
- Last updated
- 3 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant-level data will not be shared due to privacy concerns and local regulations. Only aggregate study results will be published in peer-reviewed journals and scientific meetings.
Publications
Esagian SM, Karam JA, Msaouel P, Makrakis D. Upfront Versus Deferred Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma: A Systematic Review and Individual Patient Data Meta-analysis. Eur Urol Focus. 2025 Jan;11(1):100-108. doi: 10.1016/j.euf.2024.08.002. Epub 2024 Sep 16.
PubMed 39289076Yoshino M, Ishihara H, Nemoto Y, Nakamura K, Nishimura K, Tachibana H, Fukuda H, Toki D, Yoshida K, Kobayashi H, Iizuka J, Shimmura H, Hashimoto Y, Tanabe K, Kondo T, Takagi T. Therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. Jpn J Clin Oncol. 2022 Oct 6;52(10):1208-1214. doi: 10.1093/jjco/hyac099.
PubMed 35780441Gross EE, Li M, Yin M, Orcutt D, Hussey D, Trott E, Holt SK, Dwyer ER, Kramer J, Oliva K, Gore JL, Schade GR, Lin DW, Tykodi SS, Hall ET, Thompson JA, Parikh A, Yang Y, Collier KA, Miah A, Mori-Vogt S, Hinkley M, Mortazavi A, Monk P, Folefac E, Clinton SK, Psutka SP. A multicenter study assessing survival in patients with metastatic renal cell carcinoma receiving immune checkpoint inhibitor therapy with and without cytoreductive nephrectomy. Urol Oncol. 2023 Jan;41(1):51.e25-51.e31. doi: 10.1016/j.urolonc.2022.08.013. Epub 2022 Oct 26.
PubMed 36441070Powles T, Blank C, Chowdhury S, Horenblas S, Peters J, Shamash J, Sarwar N, Boleti E, Sahdev A, O'Brien T, Berney D, Beltran L, Nathan P, Haanen J, Bex A. The outcome of patients treated with sunitinib prior to planned nephrectomy in metastatic clear cell renal cancer. Eur Urol. 2011 Sep;60(3):448-54. doi: 10.1016/j.eururo.2011.05.028. Epub 2011 May 17.
PubMed 21612860Bex A, Mulders P, Jewett M, Wagstaff J, van Thienen JV, Blank CU, van Velthoven R, Del Pilar Laguna M, Wood L, van Melick HHE, Aarts MJ, Lattouf JB, Powles T, de Jong Md PhD IJ, Rottey S, Tombal B, Marreaud S, Collette S, Collette L, Haanen J. Comparison of Immediate vs Deferred Cytoreductive Nephrectomy in Patients With Synchronous Metastatic Renal Cell Carcinoma Receiving Sunitinib: The SURTIME Randomized Clinical Trial. JAMA Oncol. 2019 Feb 1;5(2):164-170. doi: 10.1001/jamaoncol.2018.5543.
PubMed 30543350Mejean A, Ravaud A, Thezenas S, Colas S, Beauval JB, Bensalah K, Geoffrois L, Thiery-Vuillemin A, Cormier L, Lang H, Guy L, Gravis G, Rolland F, Linassier C, Lechevallier E, Beisland C, Aitchison M, Oudard S, Patard JJ, Theodore C, Chevreau C, Laguerre B, Hubert J, Gross-Goupil M, Bernhard JC, Albiges L, Timsit MO, Lebret T, Escudier B. Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma. N Engl J Med. 2018 Aug 2;379(5):417-427. doi: 10.1056/NEJMoa1803675. Epub 2018 Jun 3.
PubMed 29860937Singla N, Hutchinson RC, Ghandour RA, Freifeld Y, Fang D, Sagalowsky AI, Lotan Y, Bagrodia A, Margulis V, Hammers HJ, Woldu SL. Improved survival after cytoreductive nephrectomy for metastatic renal cell carcinoma in the contemporary immunotherapy era: An analysis of the National Cancer Database. Urol Oncol. 2020 Jun;38(6):604.e9-604.e17. doi: 10.1016/j.urolonc.2020.02.029. Epub 2020 Apr 3.
PubMed 32253116Mazzaschi G, Quaini F, Bersanelli M, Buti S. Cytoreductive nephrectomy in the era of targeted- And immuno- therapy for metastatic renal cell carcinoma: An elusive issue? A systematic review of the literature. Crit Rev Oncol Hematol. 2021 Apr;160:103293. doi: 10.1016/j.critrevonc.2021.103293. Epub 2021 Mar 2.
PubMed 33667661Zambrana F, Carril-Ajuria L, Gomez de Liano A, Martinez Chanza N, Manneh R, Castellano D, de Velasco G. Complete response and renal cell carcinoma in the immunotherapy era: The paradox of good news. Cancer Treat Rev. 2021 Sep;99:102239. doi: 10.1016/j.ctrv.2021.102239. Epub 2021 Jun 1.
PubMed 34157582Du Z, Chen W, Xia Q, Shi O, Chen Q. Trends and projections of kidney cancer incidence at the global and national levels, 1990-2030: a Bayesian age-period-cohort modeling study. Biomark Res. 2020 May 13;8:16. doi: 10.1186/s40364-020-00195-3. eCollection 2020.
PubMed 32435498
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07233668
- Acronym / sponsor ID
- IVE in mRCC / 2502-014-1611
- Conditions
- Metastatic Renal Cell Carcinoma ( mRCC)
- Keywords
- Metastatic Renal Cell Carcinoma, Immune Checkpoint Inhibitor, Cytoreductive Nephrectomy, Progression-Free Survival, Randomized Clinical Trial
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 172 participants (estimated)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Study start
- 1 Dec 2025 (estimated)
- Primary completion
- 1 Oct 2028 (estimated)
- Study completion
- 1 Feb 2029 (estimated)
- First posted
- 18 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Upfront Cytoreductive Nephrectomy (CN) | Experimental | Drug: Ipilimumab plus Nivolumab, Procedure: Cytoreductive NephrectomyParticipants 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. |
| Deferred Cytoreductive Nephrectomy (CN) | Experimental | Drug: Ipilimumab plus Nivolumab, Procedure: Cytoreductive NephrectomyParticipants 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 |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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).
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ipilimumab plus NivolumabParticipants will receive 4 cycles of ipilimumab combined with nivolumab as induction therapy, followed by nivolumab maintenance depending on randomization schedule (before or after surgery). | Drug | Deferred Cytoreductive Nephrectomy (CN), Upfront Cytoreductive Nephrectomy (CN) |
| Cytoreductive NephrectomySurgical 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. | Procedure or surgery | Deferred Cytoreductive Nephrectomy (CN), Upfront Cytoreductive Nephrectomy (CN) |
Primary outcome
Progression-Free Survival (PFS) assessed by RECIST version 1.1
Time frame: Up to 15 months after treatment initiation
Time from randomization to first documented disease progression or death from any cause, whichever occurs first. Disease progression will be assessed according to RECIST version 1.1 criteria and clinical evaluation.
11 secondary outcomes
Overall Survival (OS)
Time frame: Up to 15 months after treatment initiation
Rate and Severity of Perioperative Complications Assessed by Clavien-Dindo Classification
Time frame: Within 90 days after cytoreductive nephrectomy
Rate and Severity of Perioperative Adverse Events Assessed by CTCAE v4.0
Time frame: Within 90 days after cytoreductive nephrectomy
Radiologic Tumor Response Rate Assessed by RECIST v1.1
Time frame: At baseline, at 12 weeks (after 4 cycles of ipilimumab/nivolumab induction therapy), and every 12 weeks thereafter up to 15 months
Rate of Unresectable Tumors in the Deferred Arm
Time frame: At the time of planned deferred cytoreductive nephrectomy
Early Disease Progression Rate Within 4 Weeks Post-Nephrectomy
Time frame: Within 4 weeks of cytoreductive nephrectomy
Rate of Open vs Minimally Invasive Surgical Approach
Time frame: At time of cytoreductive nephrectomy
Extent of Surgery (e.g., Radical vs Partial Nephrectomy; Lymphadenectomy Yes/No)
Time frame: At time of cytoreductive nephrectomy
Quality of Life Assessed by FACT-Kidney Symptom Index 15-item (FKSI-15)
Time frame: Baseline, at 12 weeks (after 4 cycles of therapy), and every 12 weeks thereafter up to 15 months
Quality of Life Assessed by EORTC QLQ-C30
Time frame: Baseline, at 12 weeks (after 4 cycles of therapy), and every 12 weeks thereafter up to 15 months
Health Utility Score Assessed by EQ-5D-5L
Time frame: Baseline, at 12 weeks (after 4 cycles of therapy), and every 12 weeks thereafter up to 15 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2025.
- Background: PubMed 39289076Esagian SM, Karam JA, Msaouel P, Makrakis D. Upfront Versus Deferred Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma: A Systematic Review and Individual Patient Data Meta-analysis. Eur Urol Focus. 2025 Jan;11(1):100-108. doi: 10.1016/j.euf.2024.08.002. Epub 2024 Sep 16.
- Background: PubMed 35780441Yoshino M, Ishihara H, Nemoto Y, Nakamura K, Nishimura K, Tachibana H, Fukuda H, Toki D, Yoshida K, Kobayashi H, Iizuka J, Shimmura H, Hashimoto Y, Tanabe K, Kondo T, Takagi T. Therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. Jpn J Clin Oncol. 2022 Oct 6;52(10):1208-1214. doi: 10.1093/jjco/hyac099.
- Background: PubMed 36441070Gross EE, Li M, Yin M, Orcutt D, Hussey D, Trott E, Holt SK, Dwyer ER, Kramer J, Oliva K, Gore JL, Schade GR, Lin DW, Tykodi SS, Hall ET, Thompson JA, Parikh A, Yang Y, Collier KA, Miah A, Mori-Vogt S, Hinkley M, Mortazavi A, Monk P, Folefac E, Clinton SK, Psutka SP. A multicenter study assessing survival in patients with metastatic renal cell carcinoma receiving immune checkpoint inhibitor therapy with and without cytoreductive nephrectomy. Urol Oncol. 2023 Jan;41(1):51.e25-51.e31. doi: 10.1016/j.urolonc.2022.08.013. Epub 2022 Oct 26.
- Background: PubMed 21612860Powles T, Blank C, Chowdhury S, Horenblas S, Peters J, Shamash J, Sarwar N, Boleti E, Sahdev A, O'Brien T, Berney D, Beltran L, Nathan P, Haanen J, Bex A. The outcome of patients treated with sunitinib prior to planned nephrectomy in metastatic clear cell renal cancer. Eur Urol. 2011 Sep;60(3):448-54. doi: 10.1016/j.eururo.2011.05.028. Epub 2011 May 17.
- Background: PubMed 30543350Bex A, Mulders P, Jewett M, Wagstaff J, van Thienen JV, Blank CU, van Velthoven R, Del Pilar Laguna M, Wood L, van Melick HHE, Aarts MJ, Lattouf JB, Powles T, de Jong Md PhD IJ, Rottey S, Tombal B, Marreaud S, Collette S, Collette L, Haanen J. Comparison of Immediate vs Deferred Cytoreductive Nephrectomy in Patients With Synchronous Metastatic Renal Cell Carcinoma Receiving Sunitinib: The SURTIME Randomized Clinical Trial. JAMA Oncol. 2019 Feb 1;5(2):164-170. doi: 10.1001/jamaoncol.2018.5543.
- Background: PubMed 29860937Mejean A, Ravaud A, Thezenas S, Colas S, Beauval JB, Bensalah K, Geoffrois L, Thiery-Vuillemin A, Cormier L, Lang H, Guy L, Gravis G, Rolland F, Linassier C, Lechevallier E, Beisland C, Aitchison M, Oudard S, Patard JJ, Theodore C, Chevreau C, Laguerre B, Hubert J, Gross-Goupil M, Bernhard JC, Albiges L, Timsit MO, Lebret T, Escudier B. Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma. N Engl J Med. 2018 Aug 2;379(5):417-427. doi: 10.1056/NEJMoa1803675. Epub 2018 Jun 3.
- Background: PubMed 32253116Singla N, Hutchinson RC, Ghandour RA, Freifeld Y, Fang D, Sagalowsky AI, Lotan Y, Bagrodia A, Margulis V, Hammers HJ, Woldu SL. Improved survival after cytoreductive nephrectomy for metastatic renal cell carcinoma in the contemporary immunotherapy era: An analysis of the National Cancer Database. Urol Oncol. 2020 Jun;38(6):604.e9-604.e17. doi: 10.1016/j.urolonc.2020.02.029. Epub 2020 Apr 3.
- Background: PubMed 33667661Mazzaschi G, Quaini F, Bersanelli M, Buti S. Cytoreductive nephrectomy in the era of targeted- And immuno- therapy for metastatic renal cell carcinoma: An elusive issue? A systematic review of the literature. Crit Rev Oncol Hematol. 2021 Apr;160:103293. doi: 10.1016/j.critrevonc.2021.103293. Epub 2021 Mar 2.
- Background: PubMed 34157582Zambrana F, Carril-Ajuria L, Gomez de Liano A, Martinez Chanza N, Manneh R, Castellano D, de Velasco G. Complete response and renal cell carcinoma in the immunotherapy era: The paradox of good news. Cancer Treat Rev. 2021 Sep;99:102239. doi: 10.1016/j.ctrv.2021.102239. Epub 2021 Jun 1.
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- Individual participant dataSharing planned: No. Individual participant-level data will not be shared due to privacy concerns and local regulations. Only aggregate study results will be published in peer-reviewed journals and scientific meetings.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Chang Wook Jeong, MD, PhD principal investigator
Seoul National Universtiy Hospital
Questions about this trial
What is this clinical trial studying?
A study testing Ipilimumab plus Nivolumab and Cytoreductive Nephrectomy in people with Metastatic Renal Cell Carcinoma ( mRCC), run by Seoul National University Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 3 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chang Wook Jeong, MD, PhD (+82-2-2072-3899, drboss@snu.ac.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival (PFS) assessed by RECIST version 1.1 (time frame: Up to 15 months after treatment initiation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07233668, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2025.