Radiotherapy Combined With Tislelizumab and Irinotecan in MSS/pMMR Recurrence and Metastatic Colorectal Cancer

Phase 2

Recruiting

• Conditions: Colorectal Cancer Metastatic; Microsatellite Stable; Mismatch Repair-proficient
• Interventions: Drug: Tislelizumab; Drug: Irinotecan; Radiation: radiotherapy

• Registration Number: NCT05160727
• Lead Sponsor: Zhejiang Cancer Hospital

Brief Summary

Explore the efficacy of radiotherapy combined with Tislelizumab and irinotecan in MSS/pMMR inoperable recurrent and metastatic colorectal cancer patients; To evaluate the safety and tolerability of radiotherapy combined with Tislelizumab and irinotecan in MSS/pMMR inoperable recurrent and metastatic colorectal cancer; To evaluate the radiosensitization effects of Tslelizumab and irinotecan;

Detailed Description

Not available

Study Timeline

• Study Start: 2021-10-01
• Study First Submitted: 2021-11-16
• Status Verified: 2021-12
• Study First Submitted QC: 2021-12-02
• Study First Posted: 2021-12-16
• Last Update Submitted: 2021-12-17
• Last Update Posted: 2021-12-20
• Primary Completion: 2024-10
• Study Completion: 2024-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

1. Voluntary signing of informed consent;
2. Aged 18-70 years old, regardless of gender;
3. Histologically confirmed as inoperable recurrent or metastatic colorectal adenocarcinoma;
4. Previously received oxaliplatin and fluorouracil based chemotherapy; No previous treatment with irinotecan;
5. NGS sequencing or immunohistochemistry prompts MSS/pMMR
6. At least one measurable lesion;
7. Palliative radiotherapy is required for clinical evaluation (except radiotherapy for bone or brain metastasis);
8. ECOG scores 0-2;
9. Expected survival ≥ 6 months;
10. The organ function of the patient was normal within 7 days before treatment, and the function of important organs met certain requirements.

Exclusion Criteria

1. Pregnant or breastfeeding women;
2. There were primary lesions or metastases in the radiation field and had received radiotherapy before;
3. Previously received PD-1, PD-L1 or PD-L2 for any indication;
4. Those with other history of malignant disease in the past 5 years, except for cured skin cancer and cervical carcinoma in situ;
5. If there is an uncontrolled history of epilepsy, central nervous system disease or mental disorder, the investigator may determine that the clinical severity may hinder the signing of informed consent or affect the patient's oral medication compliance;
6. Clinically severe (ie, active) heart disease, such as symptomatic coronary heart disease, New York Heart Association (NYHA) class II or more severe congestive heart failure or severe arrhythmia requiring medication intervention (see appendix 12), or a history of myocardial infarction in the last 12 months;
7. Organ transplantation requires immunosuppressive therapy Severe uncontrolled recurrent infections, or other serious uncontrolled concomitant diseases;
8. Subject blood routine and biochemical indicators do not meet the following criteria: hemoglobin ≥ 90g / L; absolute neutrophil count (ANC)≥ 1.5 × 109 / L; Alanine transaminase (ALT), aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal; alkaline phosphatase (ALP).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment group	radiotherapy	Concurrent Chemoradiotherapy: Radiation: The dose is determined according to the treatment site and the purpose of treatment. Irinotecan: 80mg/m2/w (UGT1A1\*28 and \*6: 6/6+GG) or 65mg/m2/w (UGT1A1\*28 and \*6: 6/7+GG or 6/6+GA) or 50mg/m2/w (UGT1A1\*28 and \*6: 7/7+GG or 6/6+AA or 6/7+GA) Tislelizumab: 200mg ivgtt d1 q3w Consolidation therapy: 2 weeks after the completion of chemoradiotherapy. Irinotecan: 200mg/m2 ivgtt d1 q3w. Tislelizumab: 200mg ivgtt d1 q3w. Efficacy assessment every 3 cycles.
Treatment group	Tislelizumab	Concurrent Chemoradiotherapy: Radiation: The dose is determined according to the treatment site and the purpose of treatment. Irinotecan: 80mg/m2/w (UGT1A1\*28 and \*6: 6/6+GG) or 65mg/m2/w (UGT1A1\*28 and \*6: 6/7+GG or 6/6+GA) or 50mg/m2/w (UGT1A1\*28 and \*6: 7/7+GG or 6/6+AA or 6/7+GA) Tislelizumab: 200mg ivgtt d1 q3w Consolidation therapy: 2 weeks after the completion of chemoradiotherapy. Irinotecan: 200mg/m2 ivgtt d1 q3w. Tislelizumab: 200mg ivgtt d1 q3w. Efficacy assessment every 3 cycles.
Treatment group	Irinotecan	Concurrent Chemoradiotherapy: Radiation: The dose is determined according to the treatment site and the purpose of treatment. Irinotecan: 80mg/m2/w (UGT1A1\*28 and \*6: 6/6+GG) or 65mg/m2/w (UGT1A1\*28 and \*6: 6/7+GG or 6/6+GA) or 50mg/m2/w (UGT1A1\*28 and \*6: 7/7+GG or 6/6+AA or 6/7+GA) Tislelizumab: 200mg ivgtt d1 q3w Consolidation therapy: 2 weeks after the completion of chemoradiotherapy. Irinotecan: 200mg/m2 ivgtt d1 q3w. Tislelizumab: 200mg ivgtt d1 q3w. Efficacy assessment every 3 cycles.

Primary Outcome Measures

Name	Time	Method
Objective response rate	18 weeks after treatment completion	in radiation field

Trial Locations

Locations (1)

Zhejiang Cancer Hospital; 🇨🇳 Hangzhou, Zhejiang, China