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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT02600143

Acronym

COLIPI

Enrollment

123

Registered

2015-11-09

Start date

2013-08-31

Completion date

2019-04-30

Last updated

2024-05-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Colitis, Melanoma

Keywords

Melanoma, Colitis, Ipilimumab, Nivolumab, Pembrolizumab

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.

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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).

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
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.
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.

Countries

Netherlands

Outcome results