Frontiers in Oncology (Oct 2023)
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)
- Shujuan Zhou,
- Shujuan Zhou,
- Shujuan Zhou,
- Shujuan Zhou,
- Chenchen Wang,
- Lijun Shen,
- Lijun Shen,
- Lijun Shen,
- Lijun Shen,
- Yan Wang,
- Yan Wang,
- Yan Wang,
- Yan Wang,
- Hui Zhang,
- Hui Zhang,
- Hui Zhang,
- Hui Zhang,
- Ruiyan Wu,
- Ruiyan Wu,
- Ruiyan Wu,
- Ruiyan Wu,
- Yaqi Wang,
- Yaqi Wang,
- Yaqi Wang,
- Yaqi Wang,
- Yajie Chen,
- Yajie Chen,
- Yajie Chen,
- Yajie Chen,
- Yan Xuan,
- Yan Xuan,
- Yan Xuan,
- Yan Xuan,
- Fan Xia,
- Fan Xia,
- Fan Xia,
- Fan Xia,
- Zhen Zhang,
- Zhen Zhang,
- Zhen Zhang,
- Zhen Zhang,
- Juefeng Wan,
- Juefeng Wan,
- Juefeng Wan,
- Juefeng Wan
Affiliations
- Shujuan Zhou
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Shujuan Zhou
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shujuan Zhou
- Shanghai Clinical Research Center for Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Shujuan Zhou
- Shanghai Key Laboratory of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Chenchen Wang
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Lijun Shen
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Lijun Shen
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Lijun Shen
- Shanghai Clinical Research Center for Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Lijun Shen
- Shanghai Key Laboratory of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Yan Wang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Yan Wang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Yan Wang
- Shanghai Clinical Research Center for Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Yan Wang
- Shanghai Key Laboratory of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Hui Zhang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Hui Zhang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Hui Zhang
- Shanghai Clinical Research Center for Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Hui Zhang
- Shanghai Key Laboratory of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Ruiyan Wu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Ruiyan Wu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Ruiyan Wu
- Shanghai Clinical Research Center for Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Ruiyan Wu
- Shanghai Key Laboratory of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Yaqi Wang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Yaqi Wang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Yaqi Wang
- Shanghai Clinical Research Center for Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Yaqi Wang
- Shanghai Key Laboratory of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Yajie Chen
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Yajie Chen
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Yajie Chen
- Shanghai Clinical Research Center for Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Yajie Chen
- Shanghai Key Laboratory of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Yan Xuan
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Yan Xuan
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Yan Xuan
- Shanghai Clinical Research Center for Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Yan Xuan
- Shanghai Key Laboratory of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Fan Xia
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Fan Xia
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Fan Xia
- Shanghai Clinical Research Center for Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Fan Xia
- Shanghai Key Laboratory of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Zhen Zhang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Zhen Zhang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Zhen Zhang
- Shanghai Clinical Research Center for Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Zhen Zhang
- Shanghai Key Laboratory of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Juefeng Wan
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Juefeng Wan
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Juefeng Wan
- Shanghai Clinical Research Center for Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Juefeng Wan
- Shanghai Key Laboratory of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- DOI
- https://doi.org/10.3389/fonc.2023.1274487
- Journal volume & issue
-
Vol. 13
Abstract
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 Registrationhttps://clinicaltrials.gov/study/NCT05963490?cond=NCT05963490&rank=1, identifier NCT05963490.
Keywords
