细胞减积性肾切除术在免疫肿瘤学时代转移性肾细胞癌中的作用（SEVURO-CN）：一项多中心、前瞻性、随机试验的研究方案。
The role of cytoreductive nephrectomy in metastatic renal cell carcinoma in immune-oncology era (SEVURO-CN): study protocol for a multi-center, prospective, randomized trial.
机构信息
Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, South Korea.
Department of Urology, Yongin Severance Hospital, Yonsei University Health System, Seoul, South Korea.
出版信息
Trials. 2024 Jul 3;25(1):447. doi: 10.1186/s13063-024-08234-2.
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.
背景
在免疫肿瘤学（IO）时代，细胞减瘤性肾切除术（CN）在转移性肾细胞癌（mRCC）治疗中的作用仍不清楚。两项随机试验 CARMENA 和 SURTIME 的结果对 CN 的作用和时机提出了质疑。然而，尽管 mRCC 的系统治疗取得了最新进展，但之前的试验仅使用了靶向治疗，尚无研究充分探讨 CN 在免疫检查点抑制剂（CPI）治疗中的作用，因此迫切需要未来的研究来更好地定义 CN 的作用和时机。
方法
本研究是一项开放标签、多中心、平行、前瞻性、随机、干预性临床研究，旨在评估 CN 联合 CPIs 治疗国际肾细胞癌数据库联盟（IMDC）中危和高危 mRCC 患者的疗效。同步 mRCC 患者若有≤3 个 IMDC 风险特征，将被随机分配到三组（1、 upfront CN；2、deferred CN；和 3、systemic therapy [ST] 仅）。对于 ST，选择纳武单抗联合伊匹单抗联合方案，这是中危和高危 mRCC 的标准方案之一。主要终点是总生存期。次要终点是无进展生存期、客观缓解率、治疗相关不良事件参与者人数和手术发病率参与者人数。我们将分析肿瘤组织、循环肿瘤 DNA、尿液肿瘤 DNA 和肿瘤浸润淋巴细胞的基因突变谱。将分析肠道和尿液微生物群落。该研究将于 2022 年开始，将纳入 55 名患者。
讨论
本研究是为数不多的前瞻性随机试验之一，旨在评估 IO 时代 CN 在同步 mRCC 治疗中的获益。SEVURO-CN 试验将有助于确定 CN 的作用和时机，从而重新发现 CN 的价值。
试验注册
ClinicalTrials.gov，NCT05753839。于 2023 年 3 月 3 日注册。
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