Defining the Role of the Skin Microbiome in Immune-related Adverse Events (SKINBIOTA)

Defining the Role of the Skin Microbiome in Vitiligo and Immune-related Adverse Events in Advanced Melanoma Patients Treated With Anti-PD1

The skin microbiome has been implicated in several cutaneous autoimmune pathologies such as psoriasis and atopic dermatitis. However, its role in vitiligo and vitiligo lesions occuring in patients receiving anti-PD-1 for metastatic melanoma

Study Overview

• Status: Not yet recruiting
• Conditions: Vitiligo; Skin Melanoma
• Intervention / Treatment: Procedure: skin swabs at lesional and non-lesional sites; Procedure: skin swabs on skin

Detailed Description

Melanoma is the most dangerous skin cancer accounting for the highest skin cancer deaths. The prognosis for metastatic melanoma has improved considerably in recent years thanks to advances in the field of immunotherapy. The development of molecules blocking certain immunological "checkpoints" (checkpoints exerted by the CTLA-4 (Cytotoxic T lymphocytes Associated protein 4) and PD-1 (Programmed cell Death protein 1) has made it possible to obtain a significant improvement of the overall survival (OS) of patients treated for metastatic melanoma. Ipilimumab, an antibody blocking CTLA-4, is the first immunotherapy marketed, demonstrating for the first time a therapeutic response, however in a small number of patients (10 to 15%) and with significant toxicity (25% of grade 3-4). Subsequently, a second generation of more effective checkpoint blockers (30 to 40% good response) and less toxic, anti-PD-1 antibodies (pembrolizumab and nivolumab), quickly obtained a marketing authorization in the first line treatment of metastatic melanoma treatment and recently in an adjuvant situation after lymph node dissection in order to limit the risk of recurrence. However, despite these advances, a certain number of patients do not respond to treatment and it remains difficult to predict this therapeutic response. Furthermore, patients treated with ICI often experience cutaneous immune-related adverse events manifesting as skin rash, dermatitis, epidermal necrolysis, and in some cases as vitiligo like depigmentation of the skin, testifying to the development of a specific immunogenicity towards the melanocytes, cells causing melanoma, and responsible for a discoloration of the skin. Several studies have reported that a modification of certain bacteria in the digestive microbiota was predictive of the antitumor response to immunotherapy, while others were predictive of the appearance of significant autoimmune ICI-related toxicities (colitis). Several phase 1 studies have evaluated the impact of taking probiotics or fecal transplants on the tumor response of patients receiving immunotherapy for cancer (NCT 03819296; NCT03817125; NCT03643289). Thus by these new concepts, it would be interesting to assess the composition of the skin microbiota in patients treated with anti-PD-1 immunotherapy for the management of metastatic melanoma and developing during their follow-up vitiligo; predictive side effect of improved survival. These data will be compared to those obtained from patients with common vitiligo. This will be examined in patients skin swabs sampled at lesional and non-lesional sites. Functionally, we will characterize the microbial pathways using shotgun sequencing of microbial genomes and meta-transcriptomics (RNA sequencing of microbial communities of the skin).

• Study Type: Interventional
• Enrollment (Anticipated): 175
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Julien SENESCHAL, MD, PhD; Phone Number: +335 57 82 25 00; Email: julien.seneschal@chu-bordeaux.fr
• Study Contact Backup: Name: Maya SALEH, PhD; Phone Number: +335 57 57 11 24; Email: maya.saleh@u-bordeaux.fr

Study Locations

• France
  • Bordeaux, France, 33075
    • Service de Dermatologie - Hôpital Saint-André

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients diagnosed with Vitiligo according to usual criteria.
• Adult patients with metastatic melanoma, under anti-PD-1 who developed vitiligo
• Adult patients with metastatic melanoma who did not develop Immune related adverse events under anti-PD-1
• Adult patients with metastatic melanoma who developed vitiligo under anti-PD-1 and discontinued the treatment
• Free, informed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research).

Exclusion Criteria:

• Patients under 18 years old.
• No treatment for vitiligo in the past 4 weeks
• Patients under legal protection or unable to express their consent.
• Patients not affiliated to a health insurance system.
• Patients deprived of liberty by judiciary or administrative decision or hospitalized without consent or admitted in a sanitary or social institution for another reason than research.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: vitiligo patients; Adult patients diagnosed with Vitiligo according to usual criteria	Procedure: skin swabs at lesional and non-lesional sites; It will be examined in patients skin swabs sampled at lesional and non-lesional sites
Experimental: metastatic melanoma patients under anti-PD-1 who did not develop cutaneous irAEs; metastatic melanoma patients under anti-PD-1 who did not develop Cutaneous Immune-Related Adverse Events (cutaneous irAEs).	Procedure: skin swabs on skin; It will be examined in patients skin swabs sampled on skin
Experimental: Metastatic melanoma patients under anti-PD-1 who developed vitiligo lesions; patients with metastatic melanoma, under anti-PD-1 who developed vitiligo lesions	Procedure: skin swabs at lesional and non-lesional sites; It will be examined in patients skin swabs sampled at lesional and non-lesional sites
Experimental: metastatic melanoma patients with vitiligo lesions under anti-PD-1 who discontinued; Metastatic melanoma who developed vitiligo lesions under anti-PD-1 who discontinued the treatment	Procedure: skin swabs at lesional and non-lesional sites; It will be examined in patients skin swabs sampled at lesional and non-lesional sites

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine skin microbiota by sequencing with vitiligo in advanced melanoma patients under immune-checkpoint inhibitors (ICI) immunotherapy.	The composition of the skin microbiota will be characterized on skin swabs using shotgun sequencing of microbial genomes and meta-transcriptomics (RNA sequencing of microbial communities of the skin).	Day 1

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Collaborators: Centre National de la Recherche Scientifique, France

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2021
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: January 27, 2021
• First Submitted That Met QC Criteria: January 27, 2021
• First Posted (Actual): February 2, 2021

Study Record Updates

• Last Update Posted (Actual): February 2, 2021
• Last Update Submitted That Met QC Criteria: January 27, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: immunotherapy; checkpoint inhibitors; vitiligo; skin microbiota; metastatic melanoma.
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Pigmentation Disorders; Hypopigmentation; Melanoma; Vitiligo
• Other Study ID Numbers: CHUBX 2020/41

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No