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

doi:10.3389/fonc.2023.1274487

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)

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

Authors

Shujuan Zhou^{1

2

3

4}, Chenchen Wang⁵, Lijun Shen^{1

2

3

4}, Yan Wang^{1

2

3

4}, Hui Zhang^{1

2

3

4}, Ruiyan Wu^{1

2

3

4}, Yaqi Wang^{1

2

3

4}, Yajie Chen^{1

2

3

4}, Yan Xuan^{1

2

3

4}, Fan Xia^{1

2

3

4}, Zhen Zhang^{1

2

3

4}, Juefeng Wan^{1

2

3

4}

Affiliations

¹ Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
³ Shanghai Clinical Research Center for Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
⁴ Shanghai Key Laboratory of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
⁵ Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

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

Keywords: clinical protocol; immunotherapy; low-dose radiotherapy; metastatic colorectal cancer; regorafenib.

Associated data

ClinicalTrials.gov/NCT05963490

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the grants from the Key Clinical Specialty Project of Shanghai, the Shanghai Anticancer Association (HYXH2021096), the National Nature Science Foundation of China (82003229), the Guangzhou Shared Future Foundation (2021-DF-015).