Nodes-sparing Short-course Radiation Combined With CAPOX and Tislelizumab for MSS Middle and Low Rectal Cancer

NCT05972655 | Recruiting Phase 2

• 1 other identifier: SRRS-mRCAT
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, prospective, multicenter phase II clinical trial to evaluate modified short-course radiation (Radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) combined with CAPOX and PD-1 Inhibitor (Tislelizumab) for patients with MSS middle and low rectal cancer. A total of 32 patients will be enrolled in this trial. The primary endpoint is the rate of pathological complete response (pCR). The organ preservation rate, tumor regression grade, long-term prognosis, and adverse effects will also be analyzed.

Conditions

Low Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR) rate

  The status of pCR will be evaluated after the TME surgery.

  within 10 days after surgery

Secondary Outcomes (8)

• Tumor regression grade

  within 10 days after surgery

• Local recurrence rate(LRR)

  3 years after sugery

• Disease free survival(DFS)

  3 years after surgery

• Overall survival(OS)

  3 years after surgery

• Adverse effects rate

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

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Participants will receive 5\*5Gy 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, followed by total mesorectal excision surgery.

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

Interventions

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

Treatment Arm

Capecitabine DRUG

Capecitabine: 1000mg/m2 d1-14 q3w

Treatment Arm

Oxaliplatin DRUG

Oxaliplatin: 130mg/m2 d1 q3w

Treatment 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 cT2N+M0/cT3-4aN0/+M0, the lymph nodes are limited to the mesorectum, the circumferential resection margin is negative.
• 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) 0-1.
• No previous treatment(including anti-tumor therapy、immunotherapy or pelvic radiation).
• Adequate hematologic, hepatic, renal, thyroid and cardiac function: white blood cells ≥3500/mm3, neutrophils ≥1800/mm3, platelets ≥100,000/mm3, hemoglobin ≥100 g/L; activated partial thromboplastin time, prothrombin time and international normalized ratio ≤1.5 × ULN; aspartate aminotransferase and alanine aminotransferase ≤3.0 × upper limit of normal (ULN), bilirubin ≤1.25 × ULN, serum albumin ≥28 g/L. creatinine clearance ≥50 mL/mi, creatinine ≤1.5 × ULN;
• 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 with poorly differentiated adenocarcinoma, signet ring cell carcinoma, or mucinous adenocarcinoma.
• 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, 310012, China

RECRUITING

Related Publications (1)

• Cai C, Zhang X, Sun X, Wang H, Chen E, Chen L, Gu B, Wang J, Huang X, Lao W, Wang X, Chen M, Ding S, Du J, Song Z. Node-sparing modified short-course Radiotherapy Combined with CAPOX and Tislelizumab for locally Advanced MSS of Middle and low rectal Cancer (mRCAT): an open-label, single-arm, prospective, multicentre clinical trial. BMC Cancer. 2024 Oct 9;24(1):1247. doi: 10.1186/s12885-024-12994-0.

  PMID: 39385104 DERIVED

MeSH Terms

Interventions

spartalizumab; 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

Central Study Contacts

Zhangfa Song, M.D, PH.D

CONTACT

+86 13867421652; songzhangfa@zju.edu.cn

Cheng Cai, master

CONTACT

+86 18395995912; ColoSurg_cc@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2023
• First Posted: August 2, 2023
• Study Start: August 2, 2023
• Primary Completion: August 20, 2024
• Study Completion: May 1, 2026
• Last Updated: January 9, 2025

Record last verified: 2025-01

Locations

CN (1)