Node-sparing Short-Course Radiation Combined With CAPOX and Tislelizumab for MSS Rectal Cancer

NCT06507371 | Recruiting Phase 3

• 1 other identifier: SRRS-mRCA-III
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Rectal Cancer

Keywords

node-sparing radiation; PD-1; MSS; short-course radioation

Outcome Measures

Primary Outcomes (1)

• pathological complete response (pCR) rate

  Pathological complete response (pCR) rate

  within 10 days after completion of surgery

Secondary Outcomes (9)

• event free survival (EFS)

  3 years after randomization

• overall response rate (ORR)

  within 10 days after completion of chemotherapy

• organ preservation rate

  within 10 days after completion of chemotherapy

• Disease free survival(DFS)

  3 years after chemotherapy or surgery

• Overall survival(OS）

  3 years after chemotherapy or surgery

Study Arms (3)

Treatment Arm

EXPERIMENTAL

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.

Radiation: node-sparing modified short-course radiotherapy; Drug: PD-1 antibody; Drug: Capecitabine; Drug: Oxaliplatin

Standard Arm

EXPERIMENTAL

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; Drug: Oxaliplatin; Radiation: standard short-course radiotherapy

Exploration Arm

OTHER

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

Interventions

node-sparing modified short-course radiotherapy RADIATION

radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes: 25Gy/5Fx

Treatment Arm

PD-1 antibody DRUG

PD-1 antibody (Tislelizumab): 200mg d1 q3w

Exploration Arm; Treatment Arm

Capecitabine DRUG

Capecitabine: 1000mg/m2 d1-14 q3w

Exploration Arm; Standard Arm; Treatment Arm

Oxaliplatin DRUG

Oxaliplatin: 130mg/m2 d1 q3w

Exploration Arm; Standard Arm; Treatment Arm

standard short-course radiotherapy RADIATION

radiation targeting the tumor bed and surrounding tumor-draining lymph nodes: 25Gy/5Fx

Exploration Arm; Standard Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who have a strong willingness to preserve the anus and are willing to receive neoadjuvant therapy.
• Male or Female aged 18-75.
• 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.
• 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.
• Eastern Cooperative Oncology Group (ECOG) score 0-1.
• No previous treatment (including anti-tumor therapy, immunotherapy or pelvic radiation).
• Laboratory tests indicating no contraindications to radiotherapy, chemotherapy and immunotherapy.
• Informed consent form signed.

You may not qualify if:

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

Sponsors & Collaborators

• Sir Run Run Shaw Hospital: lead

Study Sites (1)

Sir Run Run Shao hospital

Hanzhou, Zhejiang, 310016, China

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

spartalizumab; Capecitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

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

Central Study Contacts

Zhangfa Song, M.D, PH.D

CONTACT

+86 13867421652; songzhangfa@zju.edu.cn

Cheng Cai, M.D

CONTACT

18395995912; ColoSurg_cc@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice president

Study Record Dates

• First Submitted: July 3, 2024
• First Posted: July 18, 2024
• Study Start: July 29, 2024
• Primary Completion: February 15, 2026
• Study Completion (Estimated): August 15, 2026
• Last Updated: June 26, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)