CAPOX and PD-1 Antibody Combined With or Without Radiotherapy for MSS Locally Advanced Rectal Cancer

Phase 2

Not yet recruiting

• Conditions: Locally Advanced Rectal Cancer; Neoadjuvant Therapy
• Interventions: Drug: PD-1 antibody; Drug: Capecitabine; Radiation: Short-course radiotherapy

• Registration Number: NCT06281405
• Lead Sponsor: Fudan University

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, anal preservation rate, 3-year DFS rate, etc.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-02
• Study First Submitted: 2024-02-05
• Study First Submitted QC: 2024-02-25
• Last Update Submitted: 2024-02-25
• Study First Posted: 2024-02-28
• Last Update Posted: 2024-02-28
• Study Start: 2024-03-01
• Primary Completion: 2026-06-30
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 198

Inclusion Criteria

1. Pathological confirmed adenocarcinoma;
2. Clinical stage T3-4 and/or N+;
3. The distance from anal verge ≤ 12 cm;
4. Without distance metastases;
5. Age 18-70 years old, female and male;
6. KPS ≥ 70;
7. 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;
8. With good compliance and signed the consent form.

Exclusion Criteria

1. Pregnancy or breast-feeding women;
2. Known history of other malignancies within 5 years;
3. Known history of previous anti-tumor treatment, including radiotherapy, chemotherapy, immune checkpoint inhibitors, T cell-related therapy, etc;
4. Known history of severe neurological or mental illness (such as schizophrenia, dementia or epilepsy);
5. Current severe cardiac disease (cardiac dysfunction and arrhythmia), renal dysfunction and liver dysfunction;
6. Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment;
7. Uncontrolled infection which needs systemic therapy;
8. Active autoimmune disease or immunodeficiencies, known history of organ transplantation or systematic use of immunosuppressive agents;
9. Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection
10. Allergic to any component of the therapy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Immunochemotherapy group	PD-1 antibody	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.
Radiation plus immunochemotherapy group	PD-1 antibody	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.
Radiation plus immunochemotherapy group	Short-course radiotherapy	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.
Immunochemotherapy group	Capecitabine	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.
Radiation plus immunochemotherapy group	Capecitabine	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.

Primary Outcome Measures

Name	Time	Method
Complete response (CR) rate	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 Outcome Measures

Name	Time	Method
3 year overall survival rate	From date of randomization until the date of death from any cause, assessed up to 36 months.	Rate of 3 year overall survival
Grade 3-4 adverse effects rate	From date of randomization until 3 months after the completion neoadjuvant therapy	Rate of chemotherapy, radiotherapy and immunotherapy related adverse events
3 year anal preservation rate	From date of randomization until the date of or date of death from any cause, whichever came first, assessed up to 36 months.	3 year anal preservation rate
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 3 year disease free survival
Rate of surgical complications	The surgical complications were assessed within 3 months after the surgery.	Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.
3 year local recurrence free survival rate	From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.	Rate of 3 year local recurrence free survival

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, China