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

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)

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 Overview

• Status: Recruiting
• Conditions: Neoadjuvant Therapy; Locally Advanced Rectal Cancer
• Intervention / Treatment: Drug: Capecitabine; Radiation: Short-course radiotherapy; Drug: PD-1 inhibitor; Drug: Oxaliplatin

• Study Type: Interventional
• Enrollment (Estimated): 192
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhen Zhang, MD; Phone Number: 18801735029; Email: zhen_zhang@fudan.edu.cn
• Study Contact Backup: Name: Yaqi Wang, MD; Phone Number: 18121299593; Email: 10301010093@fudan.edu.cn

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: Zhen Zhang, MD, PhD; Phone Number: 18801735029; Email: zhen_zhang@fudan.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Age 18-70 years old, female and male;
2. Pathological confirmed adenocarcinoma;
3. The distance from anal verge ≤ 10 cm;
4. MSI/MMR status: MSS/pMMR;
5. Clinical stage T3-4 and/or N+, without distance metastases;
6. 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;
7. KPS ≥ 70;
8. No radiotherapy, chemotherapy, immunotherapy, or any other anti-tumor therapy had been administered prior to enrollment;
9. 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;
10. 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 severe neurological or mental illness (such as schizophrenia, dementia or epilepsy);
4. Current severe cardiac disease (cardiac dysfunction and arrhythmia), renal dysfunction and liver dysfunction;
5. Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment;
6. Uncontrolled infection which needs systemic therapy;
7. Active autoimmune disease or immunodeficiencies, known history of organ transplantation or systematic use of immunosuppressive agents;
8. Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection;
9. Allergic to any component of the therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Capecitabine; Capecitabine: 1000mg/m2 bid d1-14 q3w; Drug: PD-1 inhibitor; PD-1 inhibitor (Toripalimab): 240mg d1 q3w; Other Names: Toripalimab; Drug: Oxaliplatin; Oxaliplatin 130mg/m2 d1 q3w
Experimental: 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.	Drug: Capecitabine; Capecitabine: 1000mg/m2 bid d1-14 q3w; Radiation: Short-course radiotherapy; Short-course radiotherapy: 25Gy/5Fx; Drug: PD-1 inhibitor; PD-1 inhibitor (Toripalimab): 240mg d1 q3w; Other Names: Toripalimab; Drug: Oxaliplatin; Oxaliplatin 130mg/m2 d1 q3w

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1 month after the surgery or the decision of W&W

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Zhen Zhang, MD, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: February 5, 2024
• First Submitted That Met QC Criteria: February 25, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Oxaliplatin; Immune Checkpoint Inhibitors; toripalimab
• Other Study ID Numbers: FDRT-2023-290-3409

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No