Identification of Predictive Parameters for Colitis in Melanoma Patients Treated With Immunotherapy.

Study Overview
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Brief Summary
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The aim of this trial is to identify biomarkers and genetic predisposition for the development of immune checkpoint related colitis.

Detailed Description
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Immunotherapy with immune checkpoint-inhibitors is standard treatment for patients with melanoma. However, in about 15% of patients treated with Ipilimumab a grade 3-4 colitis will occur. In programmed cell death protein 1 (PD1) inhibitors colitis is also seen as adverse event, although less prominent. We want to find a good predictive biomarker to select patients that are prone to colitis.So far no test is available that might be predictive whether a patient will develop a grade 3-4 colitis. The study will consists of four parts: 1.) to identify a genetic profile associated with ipilimumab-induced colitis, 2.) to identify predictive (serum or fecal) biomarkers for ipilimumab-induced colitis, 3.) to study the tissue of ipilimumab-induced colitis and 4) to study the role of the gut microbiome in the development of colitis. Patients are able to participate in one, or more parts of the study.

Official Title
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Identification of Predictive Parameters for Colitis in Melanoma Patients Treated With Immunotherapy.

Conditions
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Melanoma, Colitis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with melanoma who will be treated with immune checkpoint inhibitors (ipilimumab, nivolumab, pembrolizumab) Signed written informed consent. Able to comply with the protocol. Exclusion Criteria: 1. Patients with a pre-existing colitis (e.g. Crohn's disease, ulcerative colitis).

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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genetic predisposition for immunotherapy-induced colitis | Difference in genetic profile on 99 confirmed inflammatory bowel disease (IBD) loci between patients who develop immunotherapy-induced colitis and who do not. | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Predictive biomarkers for immunotherapy-induced colitis in stool and serum | Comparison of calprotectin levels in the stool and serum-levels of C reactive protein (CRP), endotoxin, citrulline, intestinal fatty acid-binding protein (I-FABP), calprotectin and interleukin 8 (IL8) between patients who develop immunotherapy-induced colitis and who do not. | Day 0, 21, 42, 63 | 
| Clinical scoring system of colitis | Prediction of (severity of) colitis based on symptomatology measured with the MAYO score and BRISTOL stool scale. | Day -7 to 85 | 
| Histological assessment of colon biopsies in patients that develop colitis | Immunotherapy-induced colitis will be assessed in colon biopsies when a sigmoidoscopy has to be performed for diagnostic reasons. | 1 day | 
| Analysis of the gut microbiome in stool samples | Microbiome analysis in stool collected before treatment and at 3, 6, and 9 weeks and correlation with development of immunotherapy-induced colitis. | Day 0, 21, 42, 63 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melanoma, Colitis, Ipilimumab, Nivolumab, Pembrolizumab