Tislelizumab Combined With Chemotherapy (CAPOX) in the Perioperative Treatment of MSI-H/dMMR Stage II or III Colorectal Cancer

Phase 2

Not yet recruiting

• Conditions: MSI-H Colorectal Cancer; Tislelizumab; Oxaliplatin; Capecitabine
• Interventions: Drug: Tislelizumab

• Registration Number: NCT05841134
• Lead Sponsor: The First Affiliated Hospital of Zhengzhou University

Brief Summary

This study is a multi-center, single-arm, open-label phase II clinical trial, aiming to observe and evaluate the perioperative treatment of tislelizumab combined with chemotherapy (CAPOX) in stage II or III colorectal cancer with MSI-H/dMMR Patient efficacy and safety.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-04-23
• Study First Submitted QC: 2023-04-23
• Status Verified: 2023-05
• Study First Posted: 2023-05-03
• Last Update Submitted: 2023-05-05
• Last Update Posted: 2023-05-09
• Study Start: 2023-06-01
• Primary Completion: 2024-12-31
• Study Completion: 2027-01-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

1. ECOG: 0~1;
2. Patients with colon or rectal adenocarcinoma confirmed by histology or cytology;
3. The tissue specimens are confirmed as MSI-H by PCR or NGS. If the patients are dMMR by immunohistochemistry, they need to be confirmed as MSI-H by PCR (2021 Expert Consensus on Immunotherapy for Patients with Colorectal Cancer);
4. Patients with clinical stage II or III (cT3-T4 N0 M0 or Tany N+M0, clinically positive lymph nodes are defined as any lymph node ≥ 1.0 cm);
5. Expected survival period ≥ 12 weeks;
6. The subjects voluntarily joined the study, signed the informed consent form, had good compliance, and cooperated with follow-up visits.

Exclusion Criteria

1. Have received anti-tumor therapy;
2. Have received PD-(L)1 or CTLA-4 treatment;
3. The patient has any active autoimmune disease or has a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis , hyperthyroidism; patients with vitiligo; asthma that has been completely remitted in childhood and does not require any intervention in adulthood can be included; patients with asthma requiring medical intervention with bronchodilators cannot be included);
4. Patients are using immunosuppressants or systemic hormone therapy to achieve the purpose of immunosuppression (dose>10mg/day prednisone or other equivalent hormones), and continue to use within 2 weeks before enrollment;
5. Patients with any severe and/or uncontrolled diseases
6. Urine routine prompts urine protein ≥ ++, and confirmed 24-hour urine protein quantity > 1.0g;
7. Pregnant or lactating women;
8. Patients with other malignant tumors within 5 years (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix);
9. Those who have a history of psychotropic drug abuse and cannot quit or patients with mental disorders;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tislelizumab combined with CAPOX	Tislelizumab	Successfully screened subjects will receive 4 cycles of neoadjuvant therapy with tislelizumab combined with chemotherapy (CAPOX) before surgery； undergo radical surgery 4-6 weeks after the end of the last medication; tislelizumab will be given after surgery Monoclonal antibody ± chemotherapy adjuvant therapy (the investigator judges whether to add chemotherapy based on the patient's comprehensive condition), until disease progression or unacceptable toxicity, the longest treatment is 12 months.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Pathological Complete Response (pCR)	Up to 24 months	After receiving tislelizumab combined with CAPOX neoadjuvant, the rate of pathological complete remission (after neoadjuvant therapy, for those who insist on organ preservation, combined with imaging and endoscopic examination to achieve cCR, and the biopsy result of the microscope is pathological Complete remission can be judged as pCR)

Secondary Outcome Measures

Name	Time	Method
R0 resection rates	Up to 24 months	The proportion of patients achieved a complete resection with negative margin.
Overall survival (OS)	Up to 36 months	Defined as the time from randomization to death from any cause.
Event-free survival (EFS)	Up to 36 months	Event-free survival is the time from the beginning of enrollment to the occurrence of any event, including death, disease progression, change to chemotherapy, change to chemotherapy, addition of other treatments, and occurrence of fatal or intolerable side effects
Incidence of adverse events during the treatment and follow-up (safety)	until 100 days after last patient last study drug treatment	Adverse events will be assessed during treatment and follow-up.