瑞戈非尼单药或联合高/低剂量放疗加托瑞帕利单抗作为转移性结直肠癌患者的三线治疗：一项前瞻性、随机、对照II期临床试验（SLOT）方案

Regorafenib alone or in combination with high/low-dose radiotherapy plus toripalimab as third-line treatment in patients with metastatic colorectal cancer: protocol for a prospective, randomized, controlled phase II clinical trial (SLOT).

作者信息

Zhou Shujuan, Wang Chenchen, Shen Lijun, Wang Yan, Zhang Hui, Wu Ruiyan, Wang Yaqi, Chen Yajie, Xuan Yan, Xia Fan, Zhang Zhen, Wan Juefeng

机构信息

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

出版信息

Front Oncol. 2023 Oct 5;13:1274487. doi: 10.3389/fonc.2023.1274487. eCollection 2023.

UNLABELLED

Combination strategies to improve immunotherapy response in microsatellite stable metastatic colorectal cancer (MSS mCRC) remain an unmet need. Several single-arm clinical trials have shown promising synergistic effects between regorafenib and ICIs; however, some contradictory results have also been reported. Randomized controlled trials are needed to further validate the combination of regorafenib with ICIs. In addition, low-dose radiotherapy has been demonstrated to induce local immune responses by reprogramming the tumor microenvironment when combined with high-dose radiotherapy and ICIs. In this study, we designed a prospective, randomized, controlled phase II trial to investigate the efficacy and safety of regorafenib in combination with high/low-dose radiotherapy plus toripalimab in MSS mCRC compared to regorafenib alone. Patients with MSS metastatic adenocarcinoma of the colon or rectum will be enrolled and randomly assigned into two arms: a control arm and an experimental arm. Patients in the control arm will receive regorafenib monotherapy (120 mg once daily on days 1-21 of each 28 days cycle). Patients in the experimental arm will first receive one cycle of regorafenib (80 mg once daily on days 1-21 of each 28 days cycle) and toripalimab (240mg, q3w), followed by high-dose (4-8 fractions of 8-12Gy) and low-dose (1-10Gy at 0.5-2Gy/fraction) radiotherapy, and then continue regorafenib and toripalimab treatment. The primary endpoint is the objective response rate, and the secondary endpoints are disease control rate, duration of remission, median progress-free survival, median overall survival, and adverse events. Recruitment started in August 2023 and is ongoing.

CLINICAL TRIAL REGISTRATION

https://clinicaltrials.gov/study/NCT05963490?cond=NCT05963490&rank=1, identifier NCT05963490.

未标记

改善微卫星稳定转移性结直肠癌（MSS mCRC）免疫治疗反应的联合策略仍是未满足的需求。多项单臂临床试验显示瑞戈非尼与免疫检查点抑制剂（ICIs）之间有前景的协同效应；然而，也有一些矛盾的结果被报道。需要随机对照试验来进一步验证瑞戈非尼与ICIs的联合。此外，低剂量放疗已被证明与高剂量放疗和ICIs联合时，通过重新编程肿瘤微环境可诱导局部免疫反应。在本研究中，我们设计了一项前瞻性、随机、对照II期试验，以研究与单独使用瑞戈非尼相比，瑞戈非尼联合高/低剂量放疗加托瑞帕利单抗在MSS mCRC中的疗效和安全性。患有MSS结肠或直肠转移性腺癌的患者将被纳入并随机分为两组：对照组和试验组。对照组患者将接受瑞戈非尼单药治疗（每28天周期的第1 - 21天，每日一次，120mg）。试验组患者将首先接受一个周期的瑞戈非尼（每28天周期的第1 - 21天，每日一次，80mg）和托瑞帕利单抗（240mg，每3周一次），随后进行高剂量（8 - 12Gy，4 - 8次分割）和低剂量（0.5 - 2Gy/分割，1 - 10Gy）放疗，然后继续瑞戈非尼和托瑞帕利单抗治疗。主要终点是客观缓解率，次要终点是疾病控制率、缓解持续时间、中位无进展生存期、中位总生存期和不良事件。招募于2023年8月开始，正在进行中。