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

Completed

• Conditions: Colitis; Melanoma

• Registration Number: NCT02600143
• Lead Sponsor: University Medical Center Groningen

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study Start: 2013-08
• Study First Submitted: 2015-11-03
• Study First Submitted QC: 2015-11-05
• Study First Posted: 2015-11-09
• Primary Completion: 2019-04
• Study Completion: 2019-04
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-03
• Last Update Posted: 2024-05-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 123

Inclusion Criteria

1. Patients with melanoma who will be treated with immune checkpoint inhibitors (ipilimumab, nivolumab, pembrolizumab)
2. Signed written informed consent.
3. Able to comply with the protocol.

Exclusion Criteria

1. Patients with a pre-existing colitis (e.g. Crohn's disease, ulcerative colitis).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Predictive biomarkers for immunotherapy-induced colitis in stool and serum	Day 0, 21, 42, 63	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.
Clinical scoring system of colitis	Day -7 to 85	Prediction of (severity of) colitis based on symptomatology measured with the MAYO score and BRISTOL stool scale.
Analysis of the gut microbiome in stool samples	Day 0, 21, 42, 63	Microbiome analysis in stool collected before treatment and at 3, 6, and 9 weeks and correlation with development of immunotherapy-induced colitis.
Histological assessment of colon biopsies in patients that develop colitis	1 day	Immunotherapy-induced colitis will be assessed in colon biopsies when a sigmoidoscopy has to be performed for diagnostic reasons.

Trial Locations

Locations (1)

UMCG; 🇳🇱 Groningen, Netherlands