Tumor Immunotherapy and Microbiome Analysis (TIME)

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor

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 Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

• Study Contact: Name: Rossanna C. Pezo, MD/PhD; Phone Number: 416-480-4757; Email: rossanna.pezo@sunnybrook.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Sunnybrook Health Sciences Centre
      • Contact: Rossanna C. Pezo, MD/PhD; Phone Number: 416-480-4757; Email: rossanna.pezo@sunnybrook.ca

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Adult patients with advanced/unresectable or metastatic solid tumors either planned to start standard of care treatment with ICIs or already on treatment with ICIs.

Description

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

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Subjects with advanced solid tumors starting immunotherapy; Subjects with advanced solid tumors planned to initiate standard of care immune checkpoint inhibitors
Subjects with advanced solid tumors receiving ICIs; Subjects with advanced solid tumors already receiving standard of care immune checkpoint inhibitors

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: University of Toronto; Princess Margaret Hospital, Canada
• Investigators: Principal Investigator: Rossanna C. Pezo, MD/PhD, Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2018
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: October 1, 2020
• First Submitted That Met QC Criteria: October 1, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): May 5, 2022
• Last Update Submitted That Met QC Criteria: May 4, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Microbiome; Immune Checkpoint Inhibitor; Immune-Mediated Toxicity
• Other Study ID Numbers: TIME

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