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

NCT04518280 | Completed Phase 2

• 1 other identifier: FDRT-2020-236-2156
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 3

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

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.

  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.

Secondary Outcomes (6)

• Grade 3-4 adverse effects rate

  From date of randomization until the date of death from any cause, assessed up to 5 years

• 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 overall survival rate

  From date of randomization until the date of death from any cause, assessed up to 36 months.

• 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.

Study Arms (2)

Group A

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; Drug: Oxaliplatin; Radiation: Short-course radiotherapy

Group B

EXPERIMENTAL

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.

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

Interventions

PD-1 antibody DRUG

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

Also known as: Toripalimab

Group A; Group B

Capecitabine DRUG

Capecitabine: 1000mg/m2 bid d1-14 q3w

Also known as: Xeloda

Group A; Group B

Oxaliplatin DRUG

Oxaliplatin: 130mg/m2 d1 q3w

Group A; Group B

Short-course radiotherapy RADIATION

Shor-course radiotherapy: 25Gy/5Fx

Group A; Group B

Eligibility Criteria

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

You may qualify if:

• Pathological confrmed adenocarcinoma
• Clinical stage T3-4 and/or N+
• The distance from anal verge ≤12 cm
• Without distance metastases
• Age 18-70 years old, female and male
• KPS \> =70
• 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 previous anti-tumor treatment, including radiotherapy, chemotherapy, immune checkpoint inhibitors, T cell-related therapy, etc
• 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 immunodefciencies, known history of organ transplantation or systematic use of immunosuppressive agents
• Known history of human immunodefciency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection
• 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)
• Allergic to any component of the therapy

Sponsors & Collaborators

• Fudan University: lead

Study Sites (3)

Shanghai Changhai Hospital

Shanghai, Shanghai Municipality, 200032, China

Location

Zhen Zhang

Shanghai, Shanghai Municipality, 200032, China

Location

Shanghai East Hospital

Shanghai, China

Location

Related Publications (2)

• 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.

  PMID: 38950321 DERIVED

• 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.

  PMID: 35291966 DERIVED

Related Links

• TORCH JCO 2024

MeSH Terms

Interventions

spartalizumab; toripalimab; Capecitabine; Oxaliplatin

Intervention Hierarchy (Ancestors)

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

Study Officials

• Zhen Zhang, M.D, PH.D

  Fudan University

  PRINCIPAL INVESTIGATOR

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: Professor

Study Record Dates

• First Submitted: August 15, 2020
• First Posted: August 19, 2020
• Study Start: May 1, 2021
• Primary Completion: September 1, 2023
• Study Completion: January 1, 2025
• Last Updated: January 17, 2025

Record last verified: 2025-01

Locations

CN (3)