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

NCT ID: NCT04518280

Last Updated: 2025-01-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-01
• Study Completion Date: 2025-01-01

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.

Conditions

Locally Advanced Rectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A

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 Type: EXPERIMENTAL

PD-1 antibody

Intervention Type: DRUG

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

Capecitabine

Intervention Type: DRUG

Capecitabine: 1000mg/m2 bid d1-14 q3w

Oxaliplatin

Intervention Type: DRUG

Oxaliplatin: 130mg/m2 d1 q3w

Short-course radiotherapy

Intervention Type: RADIATION

Shor-course radiotherapy: 25Gy/5Fx

Group B

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 Type: EXPERIMENTAL

PD-1 antibody

Intervention Type: DRUG

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

Capecitabine

Intervention Type: DRUG

Capecitabine: 1000mg/m2 bid d1-14 q3w

Oxaliplatin

Intervention Type: DRUG

Oxaliplatin: 130mg/m2 d1 q3w

Short-course radiotherapy

Intervention Type: RADIATION

Shor-course radiotherapy: 25Gy/5Fx

Interventions

PD-1 antibody

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

Intervention Type: DRUG

Capecitabine

Capecitabine: 1000mg/m2 bid d1-14 q3w

Intervention Type: DRUG

Oxaliplatin

Oxaliplatin: 130mg/m2 d1 q3w

Intervention Type: DRUG

Short-course radiotherapy

Shor-course radiotherapy: 25Gy/5Fx

Intervention Type: RADIATION

Other Intervention Names

Toripalimab; Xeloda

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Zhen Zhang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhen Zhang, M.D, PH.D

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Shanghai Changhai Hospital

Shanghai, Shanghai Municipality, China

Zhen Zhang

Shanghai, Shanghai Municipality, China

Shanghai East Hospital

Shanghai, , China

Countries

China

References

Xia F, Wang Y, Wang H, Shen L, Xiang Z, Zhao Y, Zhang H, Wan J, Zhang H, Wang Y, Wu R, Wang J, Yang W, Zhou M, Zhou S, Chen Y, Zhang Z, Wu X, Xuan Y, Wang R, Sun Y, Tong T, Zhang X, Wang L, Huang D, Sheng W, Yan H, Yang X, Shen Y, Xu Y, Zhao R, Mo M, Cai G, Cai S, Xu Y, Zhang Z. Randomized Phase II Trial of Immunotherapy-Based Total Neoadjuvant Therapy for Proficient Mismatch Repair or Microsatellite Stable Locally Advanced Rectal Cancer (TORCH). J Clin Oncol. 2024 Oct;42(28):3308-3318. doi: 10.1200/JCO.23.02261. Epub 2024 Jul 1.

Reference Type: DERIVED

PMID: 38950321 (View on PubMed)

Wang Y, Shen L, Wan J, Zhang H, Wu R, Wang J, Wang Y, Xu Y, Cai S, Zhang Z, Xia F. Short-course radiotherapy combined with CAPOX and Toripalimab for the total neoadjuvant therapy of locally advanced rectal cancer: a randomized, prospective, multicentre, double-arm, phase II trial (TORCH). BMC Cancer. 2022 Mar 15;22(1):274. doi: 10.1186/s12885-022-09348-z.

Reference Type: DERIVED

PMID: 35291966 (View on PubMed)

Related Links

https://pubmed.ncbi.nlm.nih.gov/38950321/

TORCH JCO 2024

Other Identifiers

FDRT-2020-236-2156

Identifier Type: -

Identifier Source: org_study_id