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The aim of this trial is to identify biomarkers and genetic predisposition for the development of immune checkpoint related colitis.
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.
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| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
1. Patients with a pre-existing colitis (e.g. Crohn's disease, ulcerative colitis).
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300
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| Name | Affiliation | Role |
|---|---|---|
| G. A.P. Hospers, MD, PhD | University Medical Center Groningen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UMCG | Groningen | 9713 GZ | Netherlands |
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| ID | Term |
|---|---|
| D008545 | Melanoma |
| D003092 | Colitis |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
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Intestinal biopsies, whole blood samples, stool samples
| 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 |
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |