Clinical trial NCT04920162: Search for New Predictive Markers of the Immune Response in Vitiligo and Melanoma
Official title: Search for New Predictive Markers of the Immune Response in Vitiligo and Melanoma (Vitilimel Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Melanoma and Vitiligo
Lead sponsor: Centre Hospitalier Universitaire de Nice
Sponsor class: OTHER
First posted: 2021-06-09
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Skin diseases can have various origins. However, a number of them are linked to an imbalance in the immune system which will lead to either an excessively strong autoimmune response or a complete lack of response against cancer cells. Indeed, both melanoma and vitiligo are pathologies where the immune system plays an important role in the progression of the disease.

Advanced stage melanoma (metastatic lymph node and / or visceral) have a poor prognosis. Although targeted therapies and immunotherapies have improved the outcome for patient however significant proportion of these patients (\~ 50%) developed resistance to therapies.

Vitiligo is a relatively common dermatosis affecting approximately 0.5% to 1% of the French population. Vitiligo results from the destruction of the melanocytes by the immune system. It is manifested by acquired depigmented macules, well limited and asymptomatic. Patients suffering from this condition have a marked decrease in their quality of life. There has been shown a strong link between vitiligo and melanoma. Indeed, patients with melanoma who develop vitiligo (\~ 9% of patients treated with anti-PD-1 drugs) have a better prognosis compared to patients who do not develop vitiligo.

Interestingly, in melanoma cases where the immune system is inactive, the investigators have identified a new molecule secreted by melanoma cells, ITGBL1, leading to the exclusion of immune cells, decreased cytokines secretion and decreased immune cell activation. It is therefore essential to better understand the regulatory mechanism of the immune system in patients with vitiligo or in patients with melanoma treated by immunotherapy in order to be able to propose new therapeutic solutions for these patients.

No study to date has investigated the expression of ITGBL1 and serum inflammatory markers during the development of melanoma. Likewise in vitiligo, if a loss of ITGBL1 is observed, new treatments could be developed in order to limit the progression of the disease by re-expressing this protein.

Thus, the investigators exploratory study will provide the first answers to the predictive value of these markers for these pathologies in order to adapt and develop new treatments.


Eligibility criteria: Inclusion Criteria:

* Patient diagnosed with non-segmental vitiligo (vitiligo)
* Vitiligo affecting more than 5% of the total body surface (vitiligo)
* Patient with unresectable stage III or stage IV skin melanoma confirmed histologically (melanoma)
* Treatment-naïve patient with an indication for anti-PD1 mono-immunotherapy with nivolumab or pembrolizumab regardless of their BRAF status (melanoma)

Exclusion Criteria:

* Segmental or mixed vitiligo (vitiligo)
* Photodermatosis or taking a photosensitizing treatment (vitiligo)
* Patient being allergic to gluten (vitiligo)
* Melanoma of unknown origin (melanoma)
* Ocular melanoma or mucous melanoma (melanoma)
* Patient with brain metastases, symptomatic or not (melanoma)
* Disease not measurable according to RECIST 1.1 criteria (melanoma)
* Patient for whom a combination of anti-PD1 and anti-CTLA-4 immunotherapy is being considered. (melanoma)
* Active autoimmune disease: chronic inflammatory bowel disease and patients with autoimmune disease that is or has been symptomatic
* Patients with autoimmune motor neuropathy
* Concomitant intake of oral immunosuppressive therapy or topical corticosteroid therapy (on vitiligo lesions) or systemic
* Organ transplant patients (kidney, liver, lung, heart, etc.)
* Patient with a history of clinically significant allergy
* History of treatment with anti-CTLA-4, anti-PD-1 or anti-PD-L1, including in an adjuvant situation
* HIV and / or HCV and / or HBV positive serologies
* Patient's refusal to do an HIV, HBV, HCV serology
* Vulnerable people (minors, patients under guardianship or guardianship, deprived of their liberty, under the protection of justice, etc.)
* Patient participating or having participated in another clinical drug trial during the month preceding inclusion
* Women who are pregnant or breastfeeding or who planned to become pregnant during the course of the study.

Primary outcomes:
measure: Changes in blood ITGBL1 expression during immunotherpay
timeFrame: 12 months
Secondary outcomes:
measure: Changes in cytokine CXCL9 expression in plasma
timeFrame: 12 months
measure: Changes in cytokine CXCL10 expression in plasma
timeFrame: 12 months
measure: Immune cells activity
timeFrame: 12 months
Other outcomes:
Locations:
city: Nice
country: France
facility: CHU de Nice
state: Provence Alpes Cote d'Azur
Study officials:
References: