Short-course Radiotherapy Based TNT Combined With PD-1 Inhibitor for Locally Advanced Rectal Cancer

Phase 2

Completed

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

• Registration Number: NCT04518280
• Lead Sponsor: Fudan University

Brief Summary

TORCH is a prospective, multicentre, randomized phase II trial. 130 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. Group A receives SCRT (25Gy/5Fx) followed by 6 cycles of Toripalimab combined with CAPOX (ToriCAPOX). Group B receives 2 cycles of ToriCAPOX followed by SCRT and 4 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, 3-year DFS rate, etc.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-08-15
• Study First Submitted QC: 2020-08-15
• Study First Posted: 2020-08-19
• Study Start: 2021-05-01
• Primary Completion: 2023-09-01
• Status Verified: 2025-01
• Study Completion: 2025-01-01
• Last Update Submitted: 2025-01-16
• Last Update Posted: 2025-01-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 130

Inclusion Criteria

1. Pathological confrmed 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 immunodefciencies, known history of organ transplantation or systematic use of immunosuppressive agents
9. Known history of human immunodefciency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection
10. Active Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (i.e., HBsAg positive or HBV DNA positive, HCV RNA positive if anti-HCV antibody testing positive)
11. Allergic to any component of the therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A	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.
Group B	PD-1 antibody	The patients will firstly receive 2 cycles of CAPOX and PD-1 antibody, then receive short-course radiotherapy (25Gy/5Fx), followed by 4 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.
Group A	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.
Group B	Short-course radiotherapy	The patients will firstly receive 2 cycles of CAPOX and PD-1 antibody, then receive short-course radiotherapy (25Gy/5Fx), followed by 4 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.
Group A	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.
Group A	Oxaliplatin	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.
Group B	Oxaliplatin	The patients will firstly receive 2 cycles of CAPOX and PD-1 antibody, then receive short-course radiotherapy (25Gy/5Fx), followed by 4 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.
Group B	Capecitabine	The patients will firstly receive 2 cycles of CAPOX and PD-1 antibody, then receive short-course radiotherapy (25Gy/5Fx), followed by 4 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	The status of cCR will be evaluated after the completion of neoadjuvant therapy. The pCR rate will be evaluated after surgery. The cCR patients who adopted W&W strategy will be included into the CR rate caluculation.	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 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
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
Rate of Surgical complications	The surgery was scheduled 2-4 weeks after the end of neoadjuvant therapy. And the surgical complications were assessed up to 5 years from the surgery.	Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.
Scores of Quality of Life	From date of randomization until the date of death from any cause, assessed up to 10 years	Quality of life will be evaluated using EORTC QLQ-C30, EORTC QLQ-CR29, LARS score and Wexner score.
Grade 3-4 adverse effects rate	From date of randomization until the date of death from any cause, assessed up to 5 years	Rate of chemotherapy, radiotherapy and immunotherapy related adverse events
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

Trial Locations

Locations (3)

Shanghai Changhai Hospital; 🇨🇳 Shanghai, Shanghai, China

Zhen Zhang; 🇨🇳 Shanghai, Shanghai, China

Shanghai East Hospital; 🇨🇳 Shanghai, China