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

Study Overview
=================
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;

Official Title
-----------------
A Multicenter Phase II Clinical Study of Radiotherapy Combined With Tislelizumab and Irinotecan in MSS/pMMR Inoperable Recurrence and Metastatic Colorectal Cancer

Conditions
-----------------
Mismatch Repair-proficient, Colorectal Cancer Metastatic, Microsatellite Stable

Intervention / Treatment
-----------------
* Drug: Tislelizumab
* Drug: Irinotecan
* Radiation: radiotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Voluntary signing of informed consent; Aged 18-70 years old, regardless of gender; Histologically confirmed as inoperable recurrent or metastatic colorectal adenocarcinoma; Previously received oxaliplatin and fluorouracil based chemotherapy; No previous treatment with irinotecan; NGS sequencing or immunohistochemistry prompts MSS/pMMR At least one measurable lesion; Palliative radiotherapy is required for clinical evaluation (except radiotherapy for bone or brain metastasis); ECOG scores 0-2; Expected survival ≥ 6 months; The organ function of the patient was normal within 7 days before treatment, and the function of important organs met certain requirements. Exclusion Criteria: Pregnant or breastfeeding women; There were primary lesions or metastases in the radiation field and had received radiotherapy before; Previously received PD-1, PD-L1 or PD-L2 for any indication; Those with other history of malignant disease in the past 5 years, except for cured skin cancer and cervical carcinoma in situ; 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; 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; Organ transplantation requires immunosuppressive therapy Severe uncontrolled recurrent infections, or other serious uncontrolled concomitant diseases; 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).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>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. | Drug: Tislelizumab<br>* 200mg ivgtt d1 q3w<br>Drug: Irinotecan<br>* Concurrent Chemoradiotherapy: 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) Consolidation therapy: 2 weeks after the completion of chemoradiotherapy. Irinotecan: 200mg/m2 ivgtt d1 q3w.<br>Radiation: radiotherapy<br>* radiotherapy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | in radiation field | 18 weeks after treatment completion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Tislelizumab, Irinotecan, colorectal cancer, mismatch repair-proficient, microsatellite stable