Immediate Versus Deferred Cytoreductive Nephrectomy With Ipilimumab/Nivolumab in mRCC

NCT07233668 | Not Yet Recruiting DMC

• 1 other identifier: 2502-014-1611
• Study Type: interventional
• Target: 172
• Locations: 0 countries
• Sites: N/A

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

Conditions

Metastatic Renal Cell Carcinoma ( mRCC)

Keywords

Metastatic Renal Cell Carcinoma; Immune Checkpoint Inhibitor; Cytoreductive Nephrectomy; Progression-Free Survival; Randomized Clinical Trial

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 15 months after treatment initiation

Secondary Outcomes (11)

• Overall Survival (OS)

  Up to 15 months after treatment initiation

• Rate and Severity of Perioperative Complications Assessed by Clavien-Dindo Classification

  Within 90 days after cytoreductive nephrectomy

• Rate and Severity of Perioperative Adverse Events Assessed by CTCAE v4.0

  Within 90 days after cytoreductive nephrectomy

• Radiologic Tumor Response Rate Assessed by RECIST v1.1

  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

  At the time of planned deferred cytoreductive nephrectomy

Study Arms (2)

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.

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

Drug: Ipilimumab plus Nivolumab; Procedure: Cytoreductive Nephrectomy

Interventions

Cytoreductive Nephrectomy 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); Upfront Cytoreductive Nephrectomy (CN)

Ipilimumab plus Nivolumab 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).

Deferred Cytoreductive Nephrectomy (CN); Upfront Cytoreductive Nephrectomy (CN)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Seoul National University Hospital: lead

Related Publications (10)

• 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.

  PMID: 39289076 BACKGROUND

• Yoshino 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.

  PMID: 35780441 BACKGROUND

• Gross 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.

  PMID: 36441070 BACKGROUND

• Powles 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.

  PMID: 21612860 BACKGROUND

• Bex 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.

  PMID: 30543350 BACKGROUND

• Mejean 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.

  PMID: 29860937 BACKGROUND

• Singla 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.

  PMID: 32253116 BACKGROUND

• Mazzaschi 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.

  PMID: 33667661 BACKGROUND

• Zambrana 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.

  PMID: 34157582 BACKGROUND

• Du 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.

  PMID: 32435498 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney 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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Chang Wook Jeong, MD, PhD

  Seoul National Universtiy Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chang Wook Jeong, MD, PhD

CONTACT

+82-2-2072-3899; drboss@snu.ac.kr

Jang Hee Han, MD, PhD

CONTACT

+82-2-2072-1486; urohan@snu.ac.kr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 3, 2025
• First Posted: November 18, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): February 1, 2029
• Last Updated: December 3, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share