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

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

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;

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer Metastatic; Microsatellite Stable; Mismatch Repair-proficient
• Intervention / Treatment: Drug: Tislelizumab; Drug: Irinotecan; Radiation: radiotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 44
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ji zhu, MD; Phone Number: +86 0571-88128142; Email: leo.zhu@126.com
• Study Contact Backup: Name: Ning Zhou, MD; Phone Number: +86 0571-88128142; Email: zhouning@zjcc.org.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • Zhejiang Cancer Hospital
      • Contact: Ji zhu, MD; Phone Number: +86 0571-88128142; Email: leo.zhu@126.com
      • Contact: Ning Zhou, MD; Phone Number: +86 0571-88128142; Email: zhouning@zjcc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment group; 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; 200mg ivgtt d1 q3w; Drug: Irinotecan; 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.; Radiation: radiotherapy; radiotherapy

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

Collaborators and Investigators

• Sponsor: Zhejiang Cancer Hospital
• Investigators: Principal Investigator: Ji Zhu, MD, Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Anticipated): October 1, 2024
• Study Completion (Anticipated): October 1, 2024

Study Registration Dates

• First Submitted: November 16, 2021
• First Submitted That Met QC Criteria: December 2, 2021
• First Posted (Actual): December 16, 2021

Study Record Updates

• Last Update Posted (Actual): December 20, 2021
• Last Update Submitted That Met QC Criteria: December 17, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: colorectal cancer; Irinotecan; Tislelizumab; microsatellite stable; mismatch repair-proficient
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Recurrence; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: CARTOnG-2104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No