RIFLE: a Phase II trial of stereotactic ablative radiotherapy combined with fruquintinib and tislelizumab in metastatic colorectal cancer

BACKGROUND: Currently, the prognosis for metastatic colorectal cancer (mCRC) still remains poor. The management of mCRC has become manifold because of the varied advances in the systemic and topical treatment approaches. For patients with limited number of metastases, radical local therapy plus systemic therapy can be a good choice to achieve long-term tumor control. In this study, we aimed to explore the efficacy and safety of the combination of fruquintinib, tislelizumab, and stereotactic ablative radiotherapy (SABR) in mCRC (RIFLE study). METHODS: RIFLE was designed as a single-center, single-arm, prospective Phase II clinical trial. A total of 68 mCRC patients who have failed the first-line standard treatment will be recruited in the safety run-in phase (n = 6) and the expansion phase (n = 62), respectively. Eligible patients will receive SABR followed by fruquintinib (5 mg, d1–14, once every day) and tislelizumab (200 mg, d1, once every 3 weeks) within 2 weeks from completion of radiation. The expansion phase starts when the safety of the treatment is determined (dose limiting toxicity occur in no more than one-sixth of patients in the run-in phase). The primary end point is the objective response rate. The secondary end points include the disease control rate, duration of response, 3-year progression-free survival rate, 3-year overall survival rate, and toxicity. CONCLUSIONS: The results of this trial will provide a novel insight into SABR in combination with PD-1 antibody and vascular endothelial growth factor receptor inhibitor in the systematic treatment of metastatic colorectal cancer, which is expected to provide new therapeutic strategies and improve the prognosis for mCRC patients. TRIAL REGISTRATION: NCT04948034 (ClinicalTrials.gov).