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The Effect of the Microbiome on Immune Checkpoint Inhibitor Response in Melanoma Patients

Completed
Conditions
Pathologic Stage IV Cutaneous Melanoma AJCC v8
Clinical Stage IV Cutaneous Melanoma AJCC v8
Interventions
Procedure: Biospecimen Collection
Procedure: Computed Tomography
Other: Laboratory Biomarker Analysis
Other: Questionnaire Administration
Registration Number
NCT05102773
Lead Sponsor
Ohio State University Comprehensive Cancer Center
Brief Summary

This pilot trial studies the effect of the microbiome on immune checkpoint inhibitors response in patients with melanoma by collecting stool and blood samples. Gut microbiome plays a critical role in response to immune checkpoint inhibitors. Studying the change in an individual's microbiome due to corticosteroid use may help researchers to determine whether an individual's microbiome can predict their response and toxicity to immune checkpoint inhibitors.

Detailed Description

PRIMARY OBJECTIVE:

I. To determine if the microbiome alpha-diversity is predictive of response (Response Evaluation Criteria in Solid Tumors \[RECIST\] version \[v\] 1.1) at a 12-week computed tomography (CT) scan or toxicity.

SECONDARY OBJECTIVE:

I. To determine the recruitment and compliance rates for longitudinal biospecimen collection, including stool, in melanoma patients.

EXPLORATORY OBJECTIVE:

I. To determine if individual microbes or their changes in relative abundance are predictive of response or toxicity.

OUTLINE:

Patients complete a Food Frequency Questionnaire (FFQ) at baseline, undergo collection of stool samples at baseline, within 2 days of starting corticosteroid treatment (if applicable), when asked for a control sample, and at 12 weeks, and undergo collection of blood samples and computed tomography (CT) at baseline and 12 weeks.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
88
Inclusion Criteria
  • Eligible patients include adults with stage III, IV melanoma, to be treated with pembrolizumab or nivolumab, regardless of other concurrent therapy or line of treatment
Exclusion Criteria
  • Patients will be excluded if they are undergoing active systemic or oral corticosteroid use at start of immune checkpoint inhibitors (ICI) cycle 1, with the exception of adrenal replacement dosing.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Ancillary-correlative (questionnaire, sample collection, CT)Laboratory Biomarker AnalysisPatients complete a FFQ at baseline, undergo collection of stool samples at baseline, within 2 days of starting corticosteroid treatment (if applicable), when asked for a control sample, and at 12 weeks, and undergo collection of blood samples and CT at baseline and 12 weeks.
Ancillary-correlative (questionnaire, sample collection, CT)Questionnaire AdministrationPatients complete a FFQ at baseline, undergo collection of stool samples at baseline, within 2 days of starting corticosteroid treatment (if applicable), when asked for a control sample, and at 12 weeks, and undergo collection of blood samples and CT at baseline and 12 weeks.
Ancillary-correlative (questionnaire, sample collection, CT)Biospecimen CollectionPatients complete a FFQ at baseline, undergo collection of stool samples at baseline, within 2 days of starting corticosteroid treatment (if applicable), when asked for a control sample, and at 12 weeks, and undergo collection of blood samples and CT at baseline and 12 weeks.
Ancillary-correlative (questionnaire, sample collection, CT)Computed TomographyPatients complete a FFQ at baseline, undergo collection of stool samples at baseline, within 2 days of starting corticosteroid treatment (if applicable), when asked for a control sample, and at 12 weeks, and undergo collection of blood samples and CT at baseline and 12 weeks.
Primary Outcome Measures
NameTimeMethod
Baseline microbiome alpha diversity in responders versus (vs) non-respondersAt 12 weeks

This analysis will follow a logistic regression structure. The dependent variable, response to treatment, will be evaluated using standardized criteria (Response Evaluation Criteria in Solid Tumors \[RECIST\] version \[v\] 1.1). Each patient will be classified as "respond", "stable" or "progression'' as a categorical variable and then binarized, with "respond" or "stable" in the category "responders", and "progression" in the category "non-responders". Independent variables will be alpha-diversity. Additional covariates will be included in the model to control for differences in age, sex, body mass index (BMI), Food Frequency Questionnaire (FFQ) dietary index, and medication history.

Baseline microbiome alpha diversity in patients prescribed corticosteroids vs those who were not prescribed corticosteroidsWithin the 12-week treatment window

This analysis will follow a logistic regression structure. The dependent variable, toxicity, will be evaluated by corticosteroid prescription. Dependent variables including alpha-diversity or individual microbes will be independent variables.

Secondary Outcome Measures
NameTimeMethod
Recruitment rates for longitudinal biospecimen collection, including stool, in melanoma patients12 weeks

Recruitment rates will be defined as the fraction of screened adults who are eligible and agree to participate within the Cutaneous Oncology Clinic, with an estimated recruitment of 30%. Will track the monthly collection of data and documented reasons for missing any scheduled collection dates. The recruitment rate will be used in combination with the variance of the biospecimen data in power calculations to estimate the sample size needed for future trials.

Compliance rates for longitudinal biospecimen collection, including stool, in melanoma patients12 weeks

Compliance will be defined as 90% of baseline, endpoint and corticosteroid collection. Will track the monthly collection of data and documented reasons for missing any scheduled collection dates. The compliance rate will be used in combination with the variance of the biospecimen data in power calculations to estimate the sample size needed for future trials.

Trial Locations

Locations (1)

Ohio State University Comprehensive Cancer Center

🇺🇸

Columbus, Ohio, United States

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