Effect of Gut Microbiota and Its Metabolites on the Efficacy of Immunotherapy in Metastatic Colorectal Cancer

Multi-omics Study of Intestinal Microecology in Patients with Colorectal Cancer Related to Immunotherapy

The purpose of this observational study is to understand the effect of gut microbiota on the efficacy of immunotherapy in patients with metastatic colorectal cancer and to explore the specific mechanisms of this process. In this way, it provides new ideas for the clinical treatment of colorectal cancer.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Neoplasms Malignant
• Intervention / Treatment: Other: treatment option-sintilimab plus fruquintinib; Other: treatment option-fruquintinib alone

Detailed Description

This study is a single-center, prospective, observational study. This study plans to enroll 50 patients with mCRC who received immunotherapy. Stool and blood samples were collected from patients with mCRC before receiving immunotherapy (baseline) and after one cycle of immunotherapy and stored immediately in a -80°C freezer. Six months after treatment with a PD-1 inhibitor in combination with fruquintinib, patients with mCRC were evaluated radiographically according to the modified RECIST1.1 criteria for immunotherapy (iRECIST) and were divided into responsive and non-responsive groups.

In this study, we intend to use metagenomic sequencing to screen the key intestinal microbiota that affect the efficacy of PD-1 inhibitors and predict their possible functional pathways in patients with metastatic colorectal cancer receiving anti-PD-1 immunotherapy. Then, proteomics and metabolomics methods were used to screen differential proteins and metabolites, and the correlation analysis with key intestinal microbiota was carried out, and the efficacy of immunotherapy in patients with mCRC was evaluated. Finally, the above findings were verified in animal models, and then the specific mechanism of intestinal microbiota affecting the efficacy of PD-1 inhibitors was explained by taking the changes in body metabolism and immunity as the starting point.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Nan Zhang; Phone Number: 18686440802; Email: zhangnan@jlu.edu.cn

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130021
      • Recruiting
      • The First Hospital of Jilin University
      • Contact: Nan Zhang; Phone Number: +8618686440802; Email: zhangnan@jlu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

A total of 50 patients with metastatic colorectal cancer who received immunotherapy from the First Hospital of Jilin University from 2024 to 2026 were included

Description

Inclusion Criteria:

• Clinical and pathological diagnosis of metastatic colorectal cancer
• 35-75 years old (both ends inclusive)
• complete clinical information
• signed informed consent

Exclusion Criteria:

• combined with severe respiratory and circulatory diseases
• combined with other malignant tumors
• recent severe active bleeding, uncontrolled active infection or active peptic ulcer
• moderate to severe renal insufficiency
• other circumstances that are judged by the investigator to be unsuitable for participating in this study

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Experimental group; sintilimab + fruquintinib	Other: treatment option-sintilimab plus fruquintinib; sintilimab plus fruquintinib
Control group; fruquintinib	Other: treatment option-fruquintinib alone; fruquintinib alone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of efficacy	Six months after treatment with a PD-1 inhibitor in combination with fruquintinib, patients with mCRC were evaluated radiographically according to the modified RECIST1.1 criteria for immunotherapy (iRECIST) and were divided into responsive and non-responsive groups. Patients are classified as responders if they achieve an objective response (complete or partial response or stable disease for at least 6 months), while patients are classified as non-responders if they have progressed on treatment or have stable disease for less than 6 months.	six months after treatment

Collaborators and Investigators

• Sponsor: The First Hospital of Jilin University
• Investigators: Study Director: Nan Zhang, The First Hospital of Jilin University

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: December 2, 2024
• First Submitted That Met QC Criteria: December 2, 2024
• First Posted (Estimated): December 4, 2024

Study Record Updates

• Last Update Posted (Estimated): December 4, 2024
• Last Update Submitted That Met QC Criteria: December 2, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Prognosis; Immunotherapy; Gut microbiota; Metastatic colorectal cancer; Metabolism
• Additional Relevant MeSH Terms: Neoplasms by Site; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Neoplasms; Colorectal Neoplasms
• Other Study ID Numbers: 2024-HS-147

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No