Short-course Radiotherapy Combined With CAPOX and PD-1 Antibody Versus Long-course Chemoradiotherapy Combined With CAPOX for Early Low-lying Rectal Cancer

Phase 2

Recruiting

• Conditions: Early Low Rectal Cancer
• Interventions: Radiation: Short-course radiotherapy; Radiation: Long-course radiotherapy; Drug: PD-1 antibody (Toripalimab); Drug: Oxaliplatin; Drug: Capecitabine

• Registration Number: NCT06462053
• Lead Sponsor: Fudan University

Brief Summary

TORCH-E2 is a prospective, multicentre, randomized phase II trial. 134 low-lying early (T1-3b/N0-1M0, distance from anal verge ≤5cm) patients will be recruited and assigned to Group 1 and Group 2 (1:1). Group 1 receives SCRT (25Gy/5Fx) followed by 4 cycles of capecitabine plus oxaliplatin (CAPOX) chemotherapy and PD-1 antibody. Group 2 receives LCRT (50Gy/25Fx) followed by 2 cycles of CAPOX. A WW option can be applied to patients achieving cCR while surgery will be recommended for those who fail to achieve 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

• Study Start: 2024-04-01
• Status Verified: 2024-06
• Study First Submitted: 2024-06-12
• Study First Submitted QC: 2024-06-12
• Last Update Submitted: 2024-06-12
• Study First Posted: 2024-06-17
• Last Update Posted: 2024-06-17
• Primary Completion: 2026-04-01
• Study Completion: 2027-03-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 134

Inclusion Criteria

1. age 18-75 years old, female and male
2. pathological confirmed adenocarcinoma
3. clinical stage T1-3bN0-1, tumor maximum diameter less than 4cm
4. the distance from anal verge less than 5 cm
5. without distance metastases
6. KPS >=70
7. with good compliance
8. microsatellite repair status is MSS/pMMR
9. without previous anti-cancer therapy or immunotherapy
10. signed the inform consent

Exclusion Criteria

1. pregnancy or breast-feeding women
2. pathological confirmed signet ring cell carcinoma
3. clinical stage T1N0 and can be resected locally
4. history of other malignancies within 5 years
5. serious medical illness, such as severe mental disorders, cardiac disease, uncontrolled infection, etc.
6. immunodeficiency disease or long-term using of immunosuppressive agents
7. baseline blood and biochemical indicators do not meet the following criteria: neutrophils≥1.5×10^9/L, Hb≥90g/L, PLT≥100×10^9/L, ALT/AST ≤2.5 ULN, Cr≤ 1 ULN
8. DPD deficiency
9. allergic to any component of the therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Short-course Radiotherapy plus immunochemotherapy group	PD-1 antibody (Toripalimab)	The patients will receive short-course radiotherapy (25Gy/5Fx, SCRT), followed by 4 cycles of CAPOX and PD-1 antibody, finally receive the TEM or TME surgery or adopt WW option.
Short-course Radiotherapy plus immunochemotherapy group	Short-course radiotherapy	The patients will receive short-course radiotherapy (25Gy/5Fx, SCRT), followed by 4 cycles of CAPOX and PD-1 antibody, finally receive the TEM or TME surgery or adopt WW option.
Long-course Radiotherapy plus chemotherapy group	Long-course radiotherapy	The patients will receive long-course radiotherapy (50Gy/25Fx,LCRT, concurrent capecitabine), followed by 2 cycles of CAPOX, finally receive the TEM or TME surgery or adopt WW option.
Short-course Radiotherapy plus immunochemotherapy group	Oxaliplatin	The patients will receive short-course radiotherapy (25Gy/5Fx, SCRT), followed by 4 cycles of CAPOX and PD-1 antibody, finally receive the TEM or TME surgery or adopt WW option.
Short-course Radiotherapy plus immunochemotherapy group	Capecitabine	The patients will receive short-course radiotherapy (25Gy/5Fx, SCRT), followed by 4 cycles of CAPOX and PD-1 antibody, finally receive the TEM or TME surgery or adopt WW option.
Long-course Radiotherapy plus chemotherapy group	Oxaliplatin	The patients will receive long-course radiotherapy (50Gy/25Fx,LCRT, concurrent capecitabine), followed by 2 cycles of CAPOX, finally receive the TEM or TME surgery or adopt WW option.
Long-course Radiotherapy plus chemotherapy group	Capecitabine	The patients will receive long-course radiotherapy (50Gy/25Fx,LCRT, concurrent capecitabine), followed by 2 cycles of CAPOX, finally receive the TEM or TME surgery or adopt WW option.

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
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
Organ preservation rate	from date of receiving neoadjuvant therapy, assessed up to 3 years	Organ preservation rate
3 year local recurrence free survival rate	From date of initiation of treatment until the date of first documented pelvic failure, assessed up to 36 months.	Rate of 3 year local recurrence free survival
3 year overall survival rate	From date of initiation of treatment until the date of death from any cause, assessed up to 36 months.	Rate of 3 year overall survival
3 year Quality of Life	From date of initiation of treatment until the date of death from any cause, assessed up to 3 years	Quality of life will be evaluated using EORTC QLQ-C30, EORTC QLQ-CR29, LARS score and Wexner score.
3 year disease free survival rate	From date of initiation of treatment 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

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, China