Pathological response and safety of FOLFOXIRI for neoadjuvant treatment of high-risk relapsed locally advanced colon cancer: study protocol for a single-arm, open-label phase II trial

INTRODUCTION: Neoadjuvant chemotherapy (NAC) has been demonstrated effective in several tumours, but its benefit has not yet been elucidated in colorectal cancer, especially locally advanced colorectal cancer (LACRC). METHODS AND ANALYSIS: This is a single-arm, open-label, prospective phase II exploratory clinical trial. Patients with LACRC will receive four cycles of NAC with 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI), followed by operation and then adjuvant chemotherapy with capecitabine and oxaliplatin for two to five cycles or single-agent capecitabine for five cycles, or observation. The primary endpoint is the rate of tumour regression grade (TRG) 0–2 in the resected tumour tissue, which is evaluated by experienced pathologists according to the Ryan R TRG grading system. Secondary endpoints include objective response rate, pathologic complete response, microscopically complete resection rate, progression-free survival, distant metastasis-free survival, overall survival, toxicity and compliance to study treatment, molecular markers, quality of life to study treatment and the number of patients with 30-day postoperative mortality. The objective of this study is to analyse the efficacy and safety of FOLFOXIRI as the NAC regimen in patients with LACRC and to identify a promising treatment strategy in this setting. ETHICS AND DISSEMINATION: Written informed consent will be required from and provided by all patients enrolled. The study protocol has been approved by the independent ethics committee of West China Hospital, Sichuan University (approval number: 2021403). This study will demonstrate the potential benefit of NAC with the FOLFOXIRI regimen. Results will be shared with policymakers and the academic community to promote the clinical management of colon cancer. TRIAL REGISTRATION NUMBER: NCT05018182.