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

September 15, 2023 updated by: Zhen Zhang, Fudan University

A Prospective Phase II Trial of Short-course Radiotherapy Based Total Neoadjuvant Therapy Combined With PD-1 Inhibitor for Locally Advanced Rectal Cancer (TORCH）

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

130

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Shanghai, China
        • Recruiting
        • Shanghai East Hospital
        • Contact:
          • Zuolin Xiang
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Recruiting
        • Zhen Zhang
        • Contact:
      • Shanghai, Shanghai, China, 200032
        • Recruiting
        • Shanghai Changhai Hospital
        • Contact:
      • Shanghai, Shanghai, China, 200032
        • Not yet recruiting
        • Shanghai Changzheng Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: PD-1 antibody
PD-1 antibody (Toripalimab): 240mg d1 q3w
Other Names:
  • Toripalimab
Drug: Oxaliplatin
Oxaliplatin: 130mg/m2 d1 q3w
Radiation: Short-course radiotherapy
Shor-course radiotherapy: 25Gy/5Fx
Drug: Capecitabine
Capecitabine: 1000mg/m2 bid d1-14 q3w
Other Names:
  • Xeloda
Experimental: 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.
Drug: PD-1 antibody
PD-1 antibody (Toripalimab): 240mg d1 q3w
Other Names:
  • Toripalimab
Drug: Oxaliplatin
Oxaliplatin: 130mg/m2 d1 q3w
Radiation: Short-course radiotherapy
Shor-course radiotherapy: 25Gy/5Fx
Drug: Capecitabine
Capecitabine: 1000mg/m2 bid d1-14 q3w
Other Names:
  • Xeloda

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete response (CR) rate
Time Frame: 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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
3 year overall survival rate
Time Frame: From date of randomization until the date of death from any cause, assessed up to 36 months.
Rate of 3 year overall survival
From date of randomization until the date of death from any cause, assessed up to 36 months.
Grade 3-4 adverse effects rate
Time Frame: 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
From date of randomization until the date of death from any cause, assessed up to 5 years
3 year disease free survival rate
Time Frame: 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
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
Time Frame: 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
From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.
Rate of Surgical complications
Time Frame: 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.
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.
Scores of Quality of Life
Time Frame: 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.
From date of randomization until the date of death from any cause, assessed up to 10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fudan University

Investigators

  • Principal Investigator: Zhen Zhang, M.D, PH.D, Fudan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2021

Primary Completion (Estimated)

October 1, 2023

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

August 15, 2020

First Submitted That Met QC Criteria

August 15, 2020

First Posted (Actual)

August 19, 2020

Study Record Updates

Last Update Posted (Actual)

September 18, 2023

Last Update Submitted That Met QC Criteria

September 15, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FDRT-2020-236-2156

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Locally Advanced Rectal Cancer

Clinical Trials on PD-1 antibody

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Norway

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe