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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Clinical Stage IV Cutaneous Melanoma AJCC v8, Pathologic Stage IV Cutaneous Melanoma AJCC v8

Intervention / Treatment
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* Procedure: Biospecimen Collection
* Procedure: Computed Tomography
* Other: Laboratory Biomarker Analysis
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Ancillary-correlative (questionnaire, sample collection, CT)<br>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. | Procedure: Biospecimen Collection<br>* Undergo collection of blood and stool<br>* Other names: Biological Sample Collection;Procedure: Computed Tomography<br>* Undergo CT<br>* Other names: tomography;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Questionnaire Administration<br>* Complete questionnaire<br>|

What is the study measuring?
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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 |