TY - JOUR
T1 - The role of cytoreductive nephrectomy in metastatic renal cell carcinoma in immune-oncology era (SEVURO-CN)
T2 - study protocol for a multi-center, prospective, randomized trial
AU - Park, Jee Soo
AU - Kim, Jongchan
AU - Jeon, Jinhyung
AU - Lee, Jongsoo
AU - Jang, Won Sik
AU - Lee, Seung Hwan
AU - Han, Woong Kyu
AU - Choi, Young Deuk
AU - Koo, Kyo Chul
AU - Cho, Kang Su
AU - Chung, Byung Ha
AU - Ham, Won Sik
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - Background: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) remains unclear in the immuno-oncology (IO) era. The results of two randomized trials, CARMENA and SURTIME, questioned the role and timing of CN. However, despite the latest advances in the systemic treatment of mRCC, previous trials have only used targeted therapy, and no studies have fully investigated the role of CN in immune checkpoint inhibitor (CPI) settings, and there is an urgent need for future studies to better define the role and timing of CN. Methods: This study is an open-label, multi-center, parallel, prospective, randomized, interventional clinical study to evaluate the efficacy of CN in combination with CPIs in mRCC patients with International mRCC Database Consortium (IMDC) intermediate- and poor-risk. Synchronous mRCC patients with ≤ 3 IMDC risk features will be randomly allocated to three groups (1, upfront CN; 2, deferred CN; and 3, systemic therapy [ST] only). For ST, the nivolumab plus ipilimumab combination regimen, one of the standard regimens for intermediate- and poor-risk mRCC, is chosen. The primary endpoint is overall survival. The secondary endpoints are progression-free survival, objective response rate, number of participants with treatment-related adverse events, and number of participants with surgical morbidity. We will analyze the genetic mutation profiles of the tumor tissue, circulating tumor DNA, urine tumor DNA, and tumor-infiltrating lymphocytes. The gut and urine microbial communities will be analyzed. The study will begin in 2022 and will enroll 55 patients. Discussion: This study is one of the few prospective randomized trials to evaluate the benefit of CN in the treatment of synchronous mRCC in the IO era. The SEVURO-CN trial will help identify the role and timing of CN, thereby rediscovering the value of CN. Trial registration: ClinicalTrials.gov, NCT05753839. Registered on 3 March 2023.
AB - Background: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) remains unclear in the immuno-oncology (IO) era. The results of two randomized trials, CARMENA and SURTIME, questioned the role and timing of CN. However, despite the latest advances in the systemic treatment of mRCC, previous trials have only used targeted therapy, and no studies have fully investigated the role of CN in immune checkpoint inhibitor (CPI) settings, and there is an urgent need for future studies to better define the role and timing of CN. Methods: This study is an open-label, multi-center, parallel, prospective, randomized, interventional clinical study to evaluate the efficacy of CN in combination with CPIs in mRCC patients with International mRCC Database Consortium (IMDC) intermediate- and poor-risk. Synchronous mRCC patients with ≤ 3 IMDC risk features will be randomly allocated to three groups (1, upfront CN; 2, deferred CN; and 3, systemic therapy [ST] only). For ST, the nivolumab plus ipilimumab combination regimen, one of the standard regimens for intermediate- and poor-risk mRCC, is chosen. The primary endpoint is overall survival. The secondary endpoints are progression-free survival, objective response rate, number of participants with treatment-related adverse events, and number of participants with surgical morbidity. We will analyze the genetic mutation profiles of the tumor tissue, circulating tumor DNA, urine tumor DNA, and tumor-infiltrating lymphocytes. The gut and urine microbial communities will be analyzed. The study will begin in 2022 and will enroll 55 patients. Discussion: This study is one of the few prospective randomized trials to evaluate the benefit of CN in the treatment of synchronous mRCC in the IO era. The SEVURO-CN trial will help identify the role and timing of CN, thereby rediscovering the value of CN. Trial registration: ClinicalTrials.gov, NCT05753839. Registered on 3 March 2023.
KW - Cytoreductive nephrectomy
KW - Immune checkpoint inhibitors
KW - Ipilimumab
KW - Kidney neoplasms
KW - Nivolumab
KW - Prospective studies
KW - Renal cell carcinoma
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U2 - 10.1186/s13063-024-08234-2
DO - 10.1186/s13063-024-08234-2
M3 - Article
C2 - 38961439
AN - SCOPUS:85197476720
SN - 1745-6215
VL - 25
JO - Trials
JF - Trials
IS - 1
M1 - 447
ER -