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).
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).
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单独或与高剂量放射疗法加上Toripalimab作为转移性结直肠癌患者的第三线治疗：前瞻性，随机，对照II期临床试验（SLOT）的方案。
DOI：
10.3389/fonc.2023.1274487
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发表时间：
2023
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
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作者：
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然是一个未满足的需求。几项单组临床试验显示，瑞戈非尼和ICI之间具有良好的协同作用;然而，也报告了一些相互矛盾的结果。需要随机对照试验来进一步验证瑞格非尼与ICI的组合。此外，低剂量放疗已被证明通过与高剂量放疗和ICI组合时重新编程肿瘤微环境来诱导局部免疫应答。在这项研究中，我们设计了一项前瞻性、随机、对照II期试验，以研究瑞戈非尼联合高/低剂量放疗加托立普利单抗治疗MSS mCRC与瑞戈非尼单药治疗相比的疗效和安全性。将入选结肠或直肠转移性腺癌MSS患者，并随机分为两组：对照组和实验组，对照组患者接受瑞戈非尼单药治疗（120 mg，每日一次，每28天为一周期，第1-21天）。实验组患者将首先接受一个周期的瑞戈非尼（80 mg，每天一次，每28天周期的第1-21天）和托立帕利单抗（240 mg，q3 w），随后接受高剂量（4-8次，8- 12 Gy）和低剂量（1- 10 Gy，0.5- 2 Gy/次）放疗，然后继续瑞戈非尼和托立帕利单抗治疗。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。招聘工作于2023年8月开始，目前仍在进行中。https://clinicaltrials.gov/study/NCT05963490? cond= NCT 05963490&rank =1，标识符NCT 05963490。
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. https://clinicaltrials.gov/study/NCT05963490?cond=NCT05963490&rank=1, identifier NCT05963490.
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影响因子：
254.7
作者：
Ciardiello, Fortunato;Ciardiello, Davide;Cervantes, Andres
通讯作者：
Cervantes, Andres
瑞戈非尼加特瑞普利单抗治疗转移性结直肠癌患者：Ib/II 期临床试验和肠道微生物组分析
DOI：
10.1016/j.xcrm.2021.100383
发表时间：
2021-09-21
期刊：
Cell reports. Medicine
影响因子：
--
作者：
Wang F;He MM;Yao YC;Zhao X;Wang ZQ;Jin Y;Luo HY;Li JB;Wang FH;Qiu MZ;Lv ZD;Wang DS;Li YH;Zhang DS;Xu RH
通讯作者：
Xu RH
影响因子：
10.9
作者：
Menon, Hari;Chen, Dawei;Welsh, James W.
通讯作者：
Welsh, James W.
影响因子：
51.1
作者：
Li, Jin;Qin, Shukui;Kim, Tae Won
通讯作者：
Kim, Tae Won
影响因子：
50.3
作者：
Klug, Felix;Prakash, Hridayesh;Beckhove, Philipp
通讯作者：
Beckhove, Philipp