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

NCT06281405 | Recruiting Phase 2

• 1 other identifier: FDRT-2023-290-3409
• Study Type: interventional
• Target: 192
• Locations: 1 country
• Sites: 1

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.

Conditions

Locally Advanced Rectal Cancer; Neoadjuvant Therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Grade 3-4 adverse effects rate

  From date of randomization until 3 months after the completion neoadjuvant therapy

• 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 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.

• 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 distant metastasis free survival rate

  From date of randomization until the date of first documented distant metastasis, assessed up to 36 months.

Study Arms (2)

Immunochemotherapy group

EXPERIMENTAL

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: PD-1 antibody; Drug: Capecitabine

Radiation plus immunochemotherapy group

EXPERIMENTAL

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: PD-1 antibody; Drug: Capecitabine; Radiation: Short-course radiotherapy

Interventions

PD-1 antibody DRUG

PD-1 antibody (Toripalimab): 240mg d1 q3w

Also known as: Toripalimab

Immunochemotherapy group; Radiation plus immunochemotherapy group

Capecitabine DRUG

Capecitabine: 1000mg/m2 bid d1-14 q3w

Immunochemotherapy group; Radiation plus immunochemotherapy group

Short-course radiotherapy RADIATION

Short-course radiotherapy: 25Gy/5Fx

Radiation plus immunochemotherapy group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• KPS ≥ 70;
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, China

RECRUITING

MeSH Terms

Interventions

spartalizumab; toripalimab; Capecitabine

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Zhen Zhang, MD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhen Zhang, MD

CONTACT

18801735029; zhen_zhang@fudan.edu.cn

Yaqi Wang, MD

CONTACT

18121299593; 10301010093@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Principal Investigator

Study Record Dates

• First Submitted: February 5, 2024
• First Posted: February 28, 2024
• Study Start: March 28, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: January 27, 2026

Record last verified: 2026-01

Locations

CN (1)