A Prospective Randomized Phase II Trial of CAPOX and PD-1 Antibody Combined With or Without Radiotherapy for Microsatellite Stable Locally Advanced Rectal Cancer (TORCH-iTNT)
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Fudan University
- Enrollment
- 192
- Locations
- 1
- Primary Endpoint
- Complete response (CR) rate
Study Overview
Brief Summary
TORCH-iTNT is a prospective, multicentre, randomized phase II trial. 198 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 (1:1). Group A receives 6 cycles of Toripalimab combined with CAPOX (ToriCAPOX). Group B receives SCRT (25Gy/5Fx) followed by 6 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, organ or anal preservation rate, 3-year DFS rate, etc.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 18-70 years old, female and male;
- •Pathological confirmed adenocarcinoma;
- •The distance from anal verge ≤ 10 cm;
- •MSI/MMR status: MSS/pMMR;
- •Clinical stage T3-4 and/or N+, without distance metastases;
- •At least one of the following factors is present: distance from the anus ≤5 cm, cT4, cN2, positive cMRF, positive cEMVI, or positive lateral lymph nodes;
- •No radiotherapy, chemotherapy, immunotherapy, or any other anti-tumor therapy had been administered prior to enrollment;
- •Baseline blood and biochemical indicators meet the following criteria: neutrophils ≥ 1.5 × 10^9/L, Hb ≥ 90 g/L, PLT ≥ 100 × 10^9/L, ALT/ AST ≤ 2.5 ULN, Cr ≤ 1 ULN;
- •With good compliance and signed the consent form.
Exclusion Criteria
- •Pregnancy or breast-feeding women;
- •Known history of other malignancies within 5 years;
- •Known history of severe neurological or mental illness (such as schizophrenia, dementia or epilepsy);
- •Current severe cardiac disease (cardiac dysfunction and arrhythmia), renal dysfunction and liver dysfunction;
- •Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment;
- •Uncontrolled infection which needs systemic therapy;
- •Active autoimmune disease or immunodeficiencies, known history of organ transplantation or systematic use of immunosuppressive agents;
- •Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection;
- •Allergic to any component of the therapy.
Arms & Interventions
Radiation plus immunochemotherapy group
The patients will receive short-course radiotherapy (25Gy/5Fx), followed by 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT while a W&W option can be applied to patients achieving cCR.
Intervention: Short-course radiotherapy (Radiation)
Immunochemotherapy group
The patients will receive 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT while a W&W option can be applied to patients achieving cCR.
Intervention: PD-1 inhibitor (Drug)
Radiation plus immunochemotherapy group
The patients will receive short-course radiotherapy (25Gy/5Fx), followed by 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT while a W&W option can be applied to patients achieving cCR.
Intervention: PD-1 inhibitor (Drug)
Radiation plus immunochemotherapy group
The patients will receive short-course radiotherapy (25Gy/5Fx), followed by 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT while a W&W option can be applied to patients achieving cCR.
Intervention: Oxaliplatin (Drug)
Immunochemotherapy group
The patients will receive 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT while a W&W option can be applied to patients achieving cCR.
Intervention: Oxaliplatin (Drug)
Immunochemotherapy group
The patients will receive 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT while a W&W option can be applied to patients achieving cCR.
Intervention: Capecitabine (Drug)
Radiation plus immunochemotherapy group
The patients will receive short-course radiotherapy (25Gy/5Fx), followed by 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT while a W&W option can be applied to patients achieving cCR.
Intervention: Capecitabine (Drug)
Outcomes
Primary Outcomes
Complete response (CR) rate
Time Frame: 1 month after the surgery or the decision of W&W
Rate of complete response (CR), including the rate of pathologic complete response (pCR) after surgery and the rate of cCR with W\&W strategy.
Secondary Outcomes
- 3 year overall survival rate(From date of randomization until the date of death from any cause, assessed up to 36 months.)
- Grade 3-4 adverse effects rate(From date of randomization until 3 months after the completion neoadjuvant therapy)
- 3 year disease free survival rate(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.)
- Rate of surgical complications(The surgical complications were assessed within 3 months after the surgery.)
- 3 year local recurrence free survival rate(From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.)
- 3 year organ or anal preservation rate(From date of randomization until the resection of rectum or anus, assessed up to 36 months.)
- 3 year distant metastasis free survival rate(From date of randomization until the date of first documented distant metastasis, assessed up to 36 months.)
Investigators
Zhen Zhang
Study Principal Investigator
Fudan University