Node-sparing Short-Course Radiation Combined With CAPOX and Tislelizumab for MSS Rectal Cancer (mRCAT-III)

Node-sparing Modified Short-Course Radiation Combined With CAPOX and Tislelizumab for MSS Locally Advanced of Middle and Low Rectal Cancer : An Randomized, Prospective, Multicenter, Open-label, Phase III Clinical Trial (mRCAT-III)

This is a randomized, prospective, multicenter, open-label, Phase III clinical trial to evaluate node-sparing modified short-course radiation (Radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) combined with CAPOX and PD-1 Inhibitor (Tislelizumab) compared with standard short-course radiation combined with CAPOX for patients with MSS middle and low rectal cancer. A total of 170 patients will be enrolled in this trial. The primary endpoint is the rate of pathological complete response (pCR). The EFS rate, ORR, organ preservation rate, long-term prognosis, and adverse effects will also be analyzed.

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: Capecitabine; Drug: Oxaliplatin; Drug: PD-1 antibody; Radiation: node-sparing modified short-course radiotherapy; Radiation: standard short-course radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zhangfa Song, M.D, PH.D; Phone Number: +86 13867421652; Email: songzhangfa@zju.edu.cn
• Study Contact Backup: Name: Cheng Cai, M.D; Phone Number: 18395995912; Email: ColoSurg_cc@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hanzhou, Zhejiang, China, 310016
      • Recruiting
      • Sir Run Run Shao hospital
      • Contact: Zhangfa Song, Dr; Phone Number: +86 13867421652; Email: songzhangfa@zju.edu.cn
      • Principal Investigator: Zhangfa Song, doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients who have a strong willingness to preserve the anus and are willing to receive neoadjuvant therapy.
2. Male or Female aged 18-75.
3. Patients diagnosed with low rectal cancer within 10 cm from the lower edge of the tumor to the anal verge by pelvic MRI and anorectoscopy, the clinical stage is cT3-4bN0/+M0, and the lymph nodes are limited to the mesorectum.
4. Histologically confirmed rectal adenocarcinoma; Genetic testing suggests MSI-L or MSS, or tumor biopsy immunohistochemistry reveals pMMR, that is, MSH1, MSH2, MSH6, and PMS2 are all positive.
5. Eastern Cooperative Oncology Group (ECOG) score 0-1.
6. No previous treatment (including anti-tumor therapy, immunotherapy or pelvic radiation).
7. Laboratory tests indicating no contraindications to radiotherapy, chemotherapy and immunotherapy.
8. Informed consent form signed.

Exclusion Criteria:

1. Patients with a previous history of malignant tumors besides rectal cancer.
2. Patients with distant metastases before enrollment.
3. Patients with positive internal or external iliac lymph nodes are assessed by MRI or CT.
4. Patients with obstruction, perforation, or bleeding that require emergency surgery.
5. Patients with severe concomitant diseases and estimated survival time ≤ 5 years.
6. Allergic to any component of the therapy.
7. Patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of therapy.
8. Patients who have received any other experimental drug (including immunotherapy) or participated in another interventional clinical trial within 30 days before screening.
9. Factors leading to study termination, such as alcoholism, drug abuse, other serious illnesses (including psychiatric disorders) requiring combination therapy, and patients with severe laboratory abnormalities.
10. Patients with congenital or acquired immune deficiency (such as HIV infection).
11. Vulnerable groups, including mentally ill, cognitively impaired, critically ill patients, minors, pregnant or lactating women, illiterate, etc.
12. Other conditions that investigators consider not suitable for this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm; Participants will receive 5*5Gy node-sparing modified short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) concurrently with CAPOX and tislelizumab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and tislelizumab, 200mg intravenous infusion d1 of each cycle. CAPOX and tislelizumab repeat every 3 weeks for 4 cycles. After treatment, digital rectal examination, pelvic MRI, endoscopy, and biopsy will be performed to evaluate the tumor regression grade. Patients will receive TME surgery after the chemo-immunotherapy, pCR rate and TRG grade will be evaluated.	Drug: Capecitabine; Capecitabine: 1000mg/m2 d1-14 q3w; Drug: Oxaliplatin; Oxaliplatin: 130mg/m2 d1 q3w; Drug: PD-1 antibody; PD-1 antibody (Tislelizumab): 200mg d1 q3w; Radiation: node-sparing modified short-course radiotherapy; radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes: 25Gy/5Fx
Experimental: Standard Arm; Participants will receive 5*5Gy standard short-course radiation (radiation targeting the tumor bed and surrounding tumor-draining lymph nodes) concurrently with CAPOX regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14. CAPOX repeat every 3 weeks for 4 cycles. After treatment, digital rectal examination, pelvic MRI, endoscopy, and biopsy will be performed to evaluate the tumor regression grade. Patients will receive TME surgery after the chemo-immunotherapy, pCR rate and TRG grade will be evaluated.	Drug: Capecitabine; Capecitabine: 1000mg/m2 d1-14 q3w; Drug: Oxaliplatin; Oxaliplatin: 130mg/m2 d1 q3w; Radiation: standard short-course radiotherapy; radiation targeting the tumor bed and surrounding tumor-draining lymph nodes: 25Gy/5Fx
Other: Exploration Arm; Participants will receive 5*5Gy standard short-course radiation (radiation targeting the tumor bed and surrounding tumor-draining lymph nodes) concurrently with CAPOX and tislelizumab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and tislelizumab, 200mg intravenous infusion d1 of each cycle. CAPOX and tislelizumab repeat every 3 weeks for 4 cycles. After treatment, digital rectal examination, pelvic MRI, endoscopy, and biopsy will be performed to evaluate the tumor regression grade. Patients will receive TME surgery after the chemo-immunotherapy, pCR rate and TRG grade will be evaluated.	Drug: Capecitabine; Capecitabine: 1000mg/m2 d1-14 q3w; Drug: Oxaliplatin; Oxaliplatin: 130mg/m2 d1 q3w; Drug: PD-1 antibody; PD-1 antibody (Tislelizumab): 200mg d1 q3w; Radiation: standard short-course radiotherapy; radiation targeting the tumor bed and surrounding tumor-draining lymph nodes: 25Gy/5Fx

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pathological complete response (pCR) rate	Pathological complete response (pCR) rate	within 10 days after completion of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse effects rate	Rate of radiotherapy, chemotherapy and immunotherapy related adverse events	From date of initiation of treatment until the date of death from any cause, assessed up to 5 years
event free survival (EFS)	the time from randomization until relapse or progression	3 years after randomization
overall response rate (ORR)	The ORR represents the proportion of patients whose tumor burden decreases by a pre-defined clinically meaningful threshold and is maintained for a minimum required duration, which included complete response (CR) rate and partial response (PR) rate	within 10 days after completion of chemotherapy
organ preservation rate	patients who are able to retain their rectum/anal sphincter after treatment, without requiring a permanent colostomy.	within 10 days after completion of chemotherapy
Disease free survival(DFS)	The three-year disease-free survival of patients.	3 years after chemotherapy or surgery
Overall survival(OS）	The three-year overall survival of patients.	3 years after chemotherapy or surgery
Rectal specific quality of life assessment via QLQ-CR29 Rectal specific quality of life assessment via QLQ-CR29 Rectal specific quality of life assessment via QLQ-CR29	Rectal specific quality of life according to European Organization for Research and Treatment of Cancer ( EORTC) Quality of life questionnaire QLQ-CR29. scale from 0 to 100, A higher scale represents better function and a higher quality of life.	Baseline and months 3, 6, 12, 24, 36, 60 after the chemotherapy or surgery
Quality of life assessment via QLQ-C30	Quality of life according to EORTC Quality of life Questionnaire QLQ-C30 version 3.0. Score range from 0 to 100 points. A higher score represents better function and a higher quality of life	Baseline and months 3, 6, 12, 24, 36, 60 after the chemotherapy or surgery
Validation of the Wexner score	The change of severity of fecal incontinence assessment according to Wexner score. a score from 0-20, where 0 is perfect continence and 20 is complete incontinence.	Baseline and months 3, 6, 12, 24, 36, 60 after the chemotherapy or surgery

Collaborators and Investigators

• Sponsor: Sir Run Run Shaw Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2024
• Primary Completion (Estimated): February 15, 2026
• Study Completion (Estimated): August 15, 2026

Study Registration Dates

• First Submitted: July 3, 2024
• First Submitted That Met QC Criteria: July 17, 2024
• First Posted (Actual): July 18, 2024

Study Record Updates

• Last Update Posted (Actual): June 26, 2025
• Last Update Submitted That Met QC Criteria: June 21, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: PD-1; MSS; node-sparing radiation; short-course radioation
• 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: SRRS-mRCA-III

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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