TORCH is a prospective, multicentre, randomized phase II trial. 130 LARC (T3-4/N+M0, distance from anal verge ≤12cm) patients will be treated with total neoadjuvant therapy (TNT) and assigned to Group A and Group B. Group A receives SCRT (25Gy/5Fx) followed by 6 cycles of Toripalimab combined with CAPOX (ToriCAPOX). Group B receives 2 cycles of ToriCAPOX followed by SCRT and 4 cycles of ToriCAPOX. TME surgery is scheduled after TNT while a watch and wait (W\&W) option can be applied to patients achieving clinical complete response (cCR). The primary endpoint is complete response (CR, pathological complete response \[pCR\] plus cCR) rate. The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, 3-year DFS rate, etc.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
130
PD-1 antibody (Toripalimab): 240mg d1 q3w
Capecitabine: 1000mg/m2 bid d1-14 q3w
Oxaliplatin: 130mg/m2 d1 q3w
Shor-course radiotherapy: 25Gy/5Fx
Shanghai Changhai Hospital
Shanghai, Shanghai Municipality, China
Zhen Zhang
Shanghai, Shanghai Municipality, China
Shanghai East Hospital
Shanghai, China
Complete response (CR) rate
Rate of complete response (CR), including the rate of pathologic complete response (pCR) after surgery and the rate of cCR with W\&W strategy.
Time frame: The status of cCR will be evaluated after the completion of neoadjuvant therapy. The pCR rate will be evaluated after surgery. The cCR patients who adopted W&W strategy will be included into the CR rate caluculation.
Grade 3-4 adverse effects rate
Rate of chemotherapy, radiotherapy and immunotherapy related adverse events
Time frame: From date of randomization until the date of death from any cause, assessed up to 5 years
3 year disease free survival rate
Rate of 3 year disease free survival
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
3 year local recurrence free survival rate
Rate of 3 year local recurrence free survival
Time frame: From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.
3 year overall survival rate
Rate of 3 year overall survival
Time frame: From date of randomization until the date of death from any cause, assessed up to 36 months.
Rate of Surgical complications
Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.
Time frame: The surgery was scheduled 2-4 weeks after the end of neoadjuvant therapy. And the surgical complications were assessed up to 5 years from the surgery.
Scores of Quality of Life
Quality of life will be evaluated using EORTC QLQ-C30, EORTC QLQ-CR29, LARS score and Wexner score.
Time frame: From date of randomization until the date of death from any cause, assessed up to 10 years
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