Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
BMJ Open. 2022 Mar 18;12(3):e055140. doi: 10.1136/bmjopen-2021-055140.
Total mesorectal excision (TME) and postoperative adjuvant chemotherapy following neoadjuvant chemoradiotherapy (CRT) is the standard treatment for locally advanced rectal cancer (LARC). However, neoadjuvant CRT has no recognised impact on reducing distant recurrence, and patients suffer from a long-lasting impairment in quality of life (QOL) associated with TME. Total neoadjuvant therapy (TNT) is an alternative approach that could reduce distant metastases and increase the proportion of patients who could safely undergo non-operative management (NOM). This study is designed to compare two TNT regimens in the context of NOM for selecting a more optimal regimen for patients with LARC.
NOMINATE trial is a prospective, multicentre, randomised phase II selection design study. Patients must have clinical stage II or III (T3-T4Nany) LARC with distal location (≤5 cm from the anal verge or for those who are candidates for abdominoperineal resection or intersphincteric resection). Patients will be randomised to either arm A consisting of CRT (50.4 Gy with capecitabine) followed by consolidation chemotherapy (six cycles of CapeOx), or arm B consisting of induction chemotherapy (three cycles of CapeOx plus bevacizumab) followed by CRT and consolidation chemotherapy (three cycles of CapeOx). In the case of clinical complete response (cCR) or near cCR, patients will progress to NOM. Response assessment involves a combination of digital rectal examination, endoscopy and MRI. The primary endpoint is the proportion of patients achieving pathological CR or cCR≥2 years, defined as the absence of local regrowth within 2 years after the start of NOM among eligible patients. Secondary endpoints include the cCR rate, near cCR rate, rate of NOM, overall survival, distant metastasis-free survival, locoregional failure-free survival, time to disease-related treatment failure, TME-free survival, permanent stoma-free survival, safety of the treatment, completion rate of the treatment and QOL. Allowing for a drop-out rate of 10%, 66 patients (33 per arm) from five institutions will be accrued.
The study protocol was approved by Wakayama Medical University Certified Review Board in December 2020. Trial results will be published in peer-reviewed international journals and on the jRCT website.
jRCTs051200121.
新辅助放化疗（CRT）后全直肠系膜切除术（TME）和术后辅助化疗是局部进展期直肠癌（LARC）的标准治疗方法。然而，新辅助 CRT 对降低远处复发没有公认的影响，而且 TME 导致患者的生活质量（QOL）长期受损。全新辅助治疗（TNT）是一种替代方法，可以减少远处转移，并增加可以安全接受非手术治疗（NOM）的患者比例。本研究旨在比较两种 TNT 方案在 NOM 背景下选择更优的 LARC 患者治疗方案。
NOMINATE 试验是一项前瞻性、多中心、随机二期选择设计研究。患者必须具有临床 II 期或 III 期（T3-T4Nany）低位 LARC（距肛缘≤5cm 或适合腹会阴切除术或间肛切除术的患者）。患者将被随机分配到 A 组，包括 CRT（50.4Gy 卡培他滨）后巩固化疗（6 个周期 CapeOx），或 B 组，包括诱导化疗（3 个周期 CapeOx 加贝伐珠单抗）后 CRT 和巩固化疗（3 个周期 CapeOx）。在临床完全缓解（cCR）或接近 cCR 的情况下，患者将进行 NOM。反应评估包括直肠指检、内窥镜和 MRI 的组合。主要终点是达到病理完全缓解或 cCR≥2 年的患者比例，定义为在 NOM 开始后 2 年内无局部复发的合格患者比例。次要终点包括 cCR 率、接近 cCR 率、NOM 率、总生存率、无远处转移生存率、无局部区域失败生存率、疾病相关治疗失败时间、TME 无复发生存率、永久性造口无生存、治疗安全性、治疗完成率和 QOL。考虑到 10%的脱落率，从五家机构招募 66 名患者（每组 33 名）。
研究方案于 2020 年 12 月获得和歌山医科大学认证审查委员会的批准。试验结果将发表在同行评议的国际期刊和 jRCT 网站上。
jRCTs051200121。
