The Combination of Immunotherapy and Neoadjuvant Short-course Radiotherapy in Early Rectal Cancer (TORCH-E)

A Prospective Phase II Trial of Immunotherapy Combined With Short-course Radiotherapy in Early Low Rectal Cancer

The study evaluates the combination of immunotherapy of PD-1 antibody and neoadjuvant short-course radiotherapy in early low rectal cancer. A total of 34 patients will receive 5*5Gy short-course radiotherapy, followed by 4 cycles of capecitabine plus oxaliplatin (CAPOX) chemotherapy and PD-1 antibody, finally receive the local excision(TEM) or total mesorectal excision (TME). The rate of complete response (cCR+pCR), Organ retention rate, long-term prognosis, and adverse effects will be analyzed.

Study Overview

• Status: Recruiting
• Conditions: Early Low Rectal Cancer
• Intervention / Treatment: Drug: PD-1 antibody; Drug: Capecitabine; Drug: Oxaliplatin; Radiation: Short-course radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 34
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhen Zhang, M.D, PH.D; Phone Number: 18801735029 18801735029; Email: zhen_zhang@fudan.edu.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Zhen Zhang, M.D, PH.D; Phone Number: 19521280960; Email: zhen_zhang@fudan.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. age 18-70 years old, female and male
2. pathological confirmed adenocarcinoma
3. clinical stage T1-3bN0, 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm; A total of 34 patients will receive 5*5Gy short-course radiotherapy, followed by 4 cycles of CAPOX chemotherapy and PD-1 antibody, finally receive the TEM or TME surgery.	Drug: PD-1 antibody; PD-1 antibody (Toripalimab): 240mg d1 q3w; Other Names: Toripalimab; Drug: Capecitabine; Capecitabine: 1000mg/m2 d1-14 q3w; Other Names: Xeloda; Drug: Oxaliplatin; Oxaliplatin: 130mg/m2 d1 q3w; Radiation: Short-course radiotherapy; Shor-course radiotherapy: 25Gy/5Fx

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Grade 3-4 adverse effects rate	Rate of chemotherapy, radiotherapy and immunotherapy related adverse events	From date of initiation of treatment until the date of death from any cause, assessed up to 5 years
3 year disease free survival rate	Rate of 3 year disease free survival	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.
3 year local recurrence free survival rate	Rate of 3 year local recurrence free survival	From date of initiation of treatment until the date of first documented pelvic failure, assessed up to 36 months.
3 year overall survival rate	Rate of 3 year overall survival	From date of initiation of treatment until the date of death from any cause, assessed up to 36 months.
10 year Quality of Life	Quality of life will be evaluated using EORTC QLQ-C30, EORTC QLQ-CR29, LARS score and Wexner score.	From date of initiation of treatment until the date of death from any cause, assessed up to 10 years
Organ preservation rate	Rate of patients who underwent organ preservation via WW or TEM after neoadjuvant therapy	from date of receiving neoadjuvant therapy, assessed up to 2 years

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2022
• Primary Completion (Actual): March 12, 2024
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: September 22, 2022
• First Submitted That Met QC Criteria: September 22, 2022
• First Posted (Actual): September 27, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 13, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Capecitabine; Oxaliplatin; Antibodies
• Other Study ID Numbers: FDRT-2022-227-2945

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in the related article, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years following related article publication.
• IPD Sharing Access Criteria: Proposals should be directed to xxx@yyy. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at a third party website (Link will to be included).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No