Short-course radiotherapy combined with CAPOX and Toripalimab for the total neoadjuvant therapy of locally advanced rectal cancer: a randomized, prospective, multicentre, double-arm, phase II trial (TORCH)

BACKGROUND: For patients with locally advanced (T3-4/N +) rectal cancer (LARC), the standard treatment is neoadjuvant chemoradiotherapy combined with total mesorectal resection, which greatly decreases local recurrence but does not improve overall survival. For patients who achieve a complete clinical response (cCR) after nCRT, a “Watch & Wait” (W&W) approach can be received to improve quality of life. Currently, total neoadjuvant therapy (TNT) has been demonstrated to increase the complete response rate and achieve early control of distant metastasis. Recent studies have shown promising synergistic effects of the combination of immunotherapy (PD-1/PD-L1 antibodies) and radiotherapy. Thus, for LARC patients, the combination of immunotherapy and TNT is likely to further improve the rate of complete response and prognosis. The disparities between induction therapy and consolidation therapy need to be investigated. METHODS: TORCH is a randomized, prospective, multicentre, double-arm, phase II trial of short-course radiotherapy (SCRT) combined with chemotherapy and immunotherapy in LARC. 130 LARC patients will be treated with the TNT approach and assigned to the consolidation arm and induction arm. The consolidation arm will receive SCRT, followed by 6 cycles of capecitabine plus oxaliplatin (CAPOX) and Toripalimab. The induction arm will first receive 2 cycles of CAPOX and Toripalimab, then receive SCRT, followed by 4 cycles of CAPOX and Toripalimab. Both groups will receive curative surgery or the W&W strategy. The primary endpoint is the complete response rate (rate of pCR plus cCR). The secondary endpoints include the grade 3–4 acute adverse effects rate, 3-year disease-free survival (DFS) rate, 3-year local recurrence-free survival (LRFS) rate, 3-year OS rate, rate of surgical complications and quality of life (QoL) scores. The “pick the winner” method is used to investigate the better treatment regimen. The trial was opened on 13th April 2021, and the first patient was recruited on 6th May 2021. DISCUSSION: TORCH will investigate whether SCRT combined with chemotherapy and Toripalimab can achieve better complete response rates, good tolerance and prognosis in LARC patients. This is the first clinical trial to compare the efficacy of induced immunotherapy and consolidative immunotherapy based on the TNT strategy. TRIAL REGISTRATION: Trial Registration Number and Date of Registration: ClinicalTrials.gov NCT04518280, August 15, 2020.