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

Fudan University

Status and phase: Enrolling; Phase 2

Conditions: Locally Advanced Rectal Cancer; Neoadjuvant Therapy

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

Study type: Interventional

Funder types: Other

Identifiers

NCT06281405

FDRT-2023-290-3409

Details and patient eligibility

About

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.

Enrollment: 192 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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192 participants in 2 patient groups

Immunochemotherapy group

Experimental group

Description:

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.

Treatment:

Drug: PD-1 antibody

Drug: Capecitabine

Radiation plus immunochemotherapy group

Experimental group

Description:

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.

Treatment:

Drug: PD-1 antibody

Drug: Capecitabine

Radiation: Short-course radiotherapy