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

Clinical Stage IV Cutaneous Melanoma AJCC v8 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05102773
• Other study ID #: OSU-19125
• Secondary ID: NCI-2020-01625
• Status: Completed
• Start date: February 10, 2020
• Est. completion date: May 5, 2022

Study information

• Verified date: April 2023
• Source: Ohio State University Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: May 5, 2022
• Est. primary completion date: May 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Clinical Stage IV Cutaneous Melanoma AJCC v8
• Melanoma
• Pathologic Stage IV Cutaneous Melanoma AJCC v8
• Skin Neoplasms

Intervention

Procedure:
• Biospecimen Collection
Undergo collection of blood and stool
• Computed Tomography
Undergo CT

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Questionnaire Administration
Complete questionnaire

Locations

Country	Name	City	State
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Ohio State University Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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
Primary	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	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
Secondary	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