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

A Pilot Study of the Effect of the Microbiome on Immune Checkpoint Inhibitor Response in Melanoma

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.

Study Overview

• Status: Completed
• Conditions: Clinical Stage IV Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Procedure: Computed Tomography; Other: Questionnaire Administration; Procedure: Biospecimen Collection

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.

• Study Type: Observational
• Enrollment (Actual): 88

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with stage III, IV melanoma, scheduled to receive pembrolizumab or nivolumab at Ohio State University, Comprehensive Cancer Center.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ancillary-correlative (questionnaire, sample collection, CT); Patients 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Other: Questionnaire Administration; Complete questionnaire; Procedure: Biospecimen Collection; Undergo collection of blood and stool; Other Names: Biological Sample Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline microbiome alpha diversity in responders versus (vs) non-responders	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.	At 12 weeks
Baseline microbiome alpha diversity in patients prescribed corticosteroids vs those who were not prescribed corticosteroids	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.	Within the 12-week treatment window

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment rates for longitudinal biospecimen collection, including stool, in melanoma patients	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.	12 weeks
Compliance rates for longitudinal biospecimen collection, including stool, in melanoma patients	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.	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbes as significant predictors in logistic regressions where the outcomes are binary (clinical response or treatment toxicity requiring corticosteroids), with the inputs as relative abundances of individual microbes	Individual microbe relative abundances will be compared between responders and non-responders with additional filtering to accommodate the sparseness of the microbiome data matrix. Specifically, microbes will be compared that are the most abundant, as well as being present in greater than 50% of the samples. An arcsine root transformation will be applied to the microbe relative abundances to approximate a Gaussian distribution, and then a generalized linear model applied where ''response'' is the response variable and individual microbes are the predictor variables. P-values will be corrected by the Bonferroni method and then visualized by volcano plot. Microbes and covariates found to be most significant in the model will be combined into a single model to estimate the percent variance explainable by these predictors. Analyses will be performed in R using the stats package.	At baseline, 12 weeks, or at corticosteroid prescription

Collaborators and Investigators

• Sponsor: Ohio State University Comprehensive Cancer Center
• Investigators: Principal Investigator: Daniel Spakowicz, PhD, Ohio State University Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2020
• Primary Completion (Actual): May 5, 2022
• Study Completion (Actual): May 5, 2022

Study Registration Dates

• First Submitted: October 20, 2021
• First Submitted That Met QC Criteria: October 20, 2021
• First Posted (Actual): November 2, 2021

Study Record Updates

• Last Update Posted (Actual): April 24, 2023
• Last Update Submitted That Met QC Criteria: April 20, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Skin Neoplasms
• Other Study ID Numbers: OSU-19125; NCI-2020-01625 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

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