Efficacy and influencing factors of Insect Compound Particle combined with chemotherapy for mismatch repair-related locally advanced stage III CRC who had undergone surgery and achieved R0 resection: a multicenter, double-blind, randomized, placebo-controlled clinical trial protocol.

Background: Colorectal cancer (CRC) is an insidious malignancy and the occurrence of chemotherapy resistance and toxicity seriously limits its clinical efficacy. Insect Compound Particle [Chong Yao Fu Fang (CYFF)] is a traditional Chinese medicine (TCM) compound based on the concepts of "invigorating spleen for strengthening vital qi" and "collateral disease theory". In long-term clinical application, it can reduce the toxicity of CRC chemotherapy and improve the anti-tumor effect. However, there is currently a lack of high-quality clinical evidence to prove the clinical efficacy and safety of CYFF in the treatment of CRC.

Methods: We plan to include 262 patients with locally advanced stage III CRC who had undergone surgery and achieved R0 resection. These patients will be randomized into a CYFF group (treated with CYFF combined with chemotherapy) and a control group (treated with placebo plus chemotherapy) at a 1:1 ratio. The patients were routinely followed-up every 2 weeks within 2 months and every 4 weeks after 2 months after the treatment, every 3 months within 1 year, and every 6 months after 1 year. The primary endpoint is disease-free survival (DFS), defined as the time from random assignment to recurrence of primary CRC or death from any cause. The secondary endpoints include overall survival (OS) (defined as the time from randomization to death from any cause), safety [any adverse events (AEs)], and the Colorectal Cancer-Specific Quality of Life Questionnaire (QLQ-CR38) score.

Conclusions: Compared with previous studies, our current study applies CYFF plus basic adjuvant chemotherapy, which is expected to achieve better efficacy and longer survival than standard chemotherapy, and reduce the toxic and side effects of chemotherapy, improve the safety of clinical treatment. In addition, our present study is the first clinical study to evaluate the safety and efficacy of CYFF in combination with chemotherapy in the treatment of stage III CRC after R0 resection.

Trial Registration: This clinical trial has been registered in the Chinese Clinical Trial Registry (ChiCTR) (registration No. ChiCTR2000037568; August 28, 2020).