Tumor Immunotherapy and Microbiome Analysis

Recruiting

• Conditions: Advanced Solid Tumor

• Registration Number: NCT04579978
• Lead Sponsor: Sunnybrook Health Sciences Centre

Brief Summary

The composition of the gut microbiome has been associated with response and the development of toxicities on immune checkpoint inhibitors (ICIs) in multiple tumor types. The aim of this study is to examine the gut microbiome composition in patients undergoing standard of care treatment for advanced/unresectable and/or metastatic solid tumors with ICIs. Fecal samples and peripheral blood samples will be collected to further characterize the diversity of gut bacteria and to study potential mechanisms by which gut bacteria impact the immune response.

Detailed Description

This is a prospective study of gut microbial markers. Patients with histologically confirmed advanced/unresectable or metastatic solid tumors who are planned to initiate standard of care ICIs or are undergoing standard of care treatment with ICIs will be approached for participation in the study.

Study Timeline

• Study Start: 2018-04-01
• Study First Submitted: 2020-10-01
• Study First Submitted QC: 2020-10-01
• Study First Posted: 2020-10-08
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-04
• Last Update Posted: 2022-05-05
• Primary Completion: 2023-12
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Sign written and voluntary informed consent
• Adult patients aged >=18, male or female
• Eastern Cooperative Group (ECOG) performance status 0-2
• Histologic diagnosis of an advanced/unresectable or metastatic solid tumor
• Measurable disease as per RECIST 1.1 criteria
• Be suitable for or receiving ICI treatment
• Prior immunotherapy allowed
• Be willing and able to provide fecal and blood specimens for analysis as per protocol

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Exclusion Criteria

• Subjects with a history of inflammatory bowel disease, chronic diarrhea or malabsorption syndromes and significant prior bowel resection as judged by the study investigator

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Relative abundance and composition of immunotherapy response-associated bacterial species in patients with advanced/unresectable or metastatic solid tumors	6 months	Fecal microbial composition analyzed by 16S rRNA and metagenomic sequencing
Relative abundance and composition of immunotherapy toxicity-associated bacterial species in patients with advanced/unresectable or metastatic solid tumors	12 months	Fecal microbial composition analyzed by 16S rRNA and metagenomic sequencing; IgA sequencing of fecal samples from patients who develop diarrhea/colitis

Secondary Outcome Measures

Name	Time	Method
Relative abundance of bacterial DNA in peripheral blood samples	6 months	Blood microbial abundance measured via qPCR
Changes in immune cell subsets in the systemic circulation upon progression on ICIs correlated with changes in microbiome composition	2 years	Flow cytometry of blood at baseline and at development of progressive disease and analysis of microbiome composition at baseline and at development of progressive disease
Identification of serum metabolites in systemic circulation and correlation with intestinal microbiome composition	6 months	Analysis of serum metabolites using chromatography coupled to tandem mass spectrometry
Changes in the composition of the intestinal microbiome induced by ICIs	6 months	Fecal microbial composition analyzed by 16S rRNA and metagenomic sequencing

Trial Locations

Locations (1)

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada