NCT05856565

Brief Summary

In the last decade, the advent of immunotherapies with inhibitors of immune checkpoints, such as anti-PD-1 and anti-CTLA-4, has revolutionized the treatment of advanced or metastatic melanoma. However, the clinical benefit remains limited to a subset of patients. Identifying the patients most likely to benefit from these novel therapies (and avoiding unnecessary toxicity in non-responding patients) is therefore critical. Previous studies found a significant link between the high mutational load of a tumor (TMB) and its response to anti-PD-1 monotherapy, regardless of the histological type of cancer. Unfortunately, TMB measurement is expensive, and requires extensive sequencing approaches difficult to implement in clinical practice. I have shown that melanomas known to be secondary to mutagenic ultraviolet rays (UVR) often carry a high TMB. The cumulative UVR damage translates into visible stigmas termed "dermatoheliosis" on patients' skin, easy to recognize with the naked eye of the clinician around the scar of the primary melanoma. My project proposes to establish, for the first time, dermatoheliosis as a novel predictive factor of response to anti-PD-1 immunotherapy, to be used within multidisciplinary tumor boards as a powerful decision-support tool to select the best treatment option. Specifically, I will 1) develop, validate and test in a prospective manner, an artificial intelligence (AI)-based algorithm, to assess features of pericicatricial dermatoheliosis based on a collection of photographs obtained from patients with unresectable locally advanced or metastatic melanoma 2) demonstrate the link between dermatoheliosis, TMB, immune and treatment response by characterizing pericicatricial skin single cell transcriptomics, as well as tumor DNA, RNA and host immunological profiles of the patients. This directly accessible, non-invasive, surrogate marker for TMB will be a game changer in clinical practice and will subsequently be translated to other skin cancers.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
700

participants targeted

Target at P75+ for all trials

Timeline
27mo left

Started Jul 2023

Longer than P75 for all trials

Geographic Reach
1 country

20 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress56%
Jul 2023Jul 2028

First Submitted

Initial submission to the registry

April 20, 2023

Completed
22 days until next milestone

First Posted

Study publicly available on registry

May 12, 2023

Completed
2 months until next milestone

Study Start

First participant enrolled

July 24, 2023

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 24, 2028

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 24, 2028

Last Updated

April 15, 2026

Status Verified

April 1, 2026

Enrollment Period

5 years

First QC Date

April 20, 2023

Last Update Submit

April 14, 2026

Conditions

Outcome Measures

Primary Outcomes (1)

  • Predictive performance of tumor progression score

    The predictive score for tumor progression at 6 months will be calculated from the photograph of the excision scar of the patient's primary tumor, as well as the clinical characteristics associated with the prognosis: patient age, sex, phototype, anatomical location and Breslow index of the primary tumour, stage of the skin cancer and WHO performance status at the initiation of the treatment, nature of the treatment administered

    after 6 months

Study Arms (2)

Retrospective

Photograph

Other: Photo

Prospective

Other: Photo

Interventions

PhotoOTHER

Photography intake

ProspectiveRetrospective

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

700 adult patients' cohorts (500 Retrospective and 200 Prospective cohorts), with an unresectable locally advanced or metastatic melanoma skin cancer, insured under a health insurance scheme and for which we will analyze the dermatoheliosis images and the profile data of response to 1st, 2nd and 3rd line of systemic treatment (best observed response, progression-free survival and overall survial).

You may qualify if:

  • ▪ Adult patients with inoperable stage III or IV melanoma, or inoperable skin carcinoma (squamous cell carcinoma or basal cell carcinoma).
  • Retrospective cohort: patients who have received curative treatment with anti-PD1, +/- anti-CTLA-4 or anti-LAG-3 for their skin cancer for at least 90 days, with at least 6 months of follow-up, without immunosuppression and whose primary tumour site is not altered by concomitant dermatosis. Adjuvant immunotherapy is tolerated if it was stopped at least 6 months before the start of curative treatment. Interferon is also tolerated if it was stopped at least 6 months before the start of curative treatment. Radiotherapy is tolerated if it did not take place at the site of the primary melanoma scar. For squamous cell carcinomas, prior radiotherapy on the scar is acceptable (it must simply not have been administered during the period of anti-PD-1 treatment in order to be able to reliably assess the response).
  • Inoperable primary tumours are eligible. Targeted therapy is accepted before the start of curative treatment with immunotherapy.
  • Chemotherapy is not accepted prior to the initiation of curative treatment with immunotherapy.
  • ▪ Prospective cohort: Patients who have not received immunotherapy for the management of their skin cancer at the start of curative treatment with anti-PD-1, +/- anti-CTLA-4 or anti-LAG-3.
  • Adjuvant immunotherapy is tolerated if it has been discontinued for at least 6 months prior to the start of curative treatment. Interferon is also tolerated if it has been discontinued for at least 6 months prior to the start of curative treatment. Radiotherapy is tolerated if it has not been administered at the site of the primary cancer scar.
  • Targeted therapy is accepted before starting curative treatment with anti-PD-1, +/- anti-CTLA-4 or anti-LAG-3.
  • Chemotherapy is not accepted before the start of curative treatment with anti-PD-1, +/- anti-CTLA-4 or anti-LAG-3.
  • ▪ Patients who have agreed to participate in the research and have signed an image rights authorisation form.

You may not qualify if:

  • Retrospective cohort: Patients who have received curative treatment with anti-PD-1, +/- anti-CTLA-4 or anti-LAG-3 for skin cancer for less than 90 days
  • Patients who received adjuvant immunotherapy within 6 months prior to curative treatment
  • Patients who received chemotherapy prior to curative treatment
  • Patients whose primary skin cancer site cannot be photographed (e.g. choroidal melanomas, mucosal melanomas, with the exception of vulvar or penile melanomas, etc.).
  • Patients treated with systemic corticosteroids (dose greater than 10 mg/day) at the start of the immunotherapy in question,
  • Patients who are immunocompromised (associated blood disorder, human immunodeficiency virus infection, transplant patients, etc.) at the start of immunotherapy,
  • Patients with iatrogenic peri-scar vitiligo,
  • Patients who have refused to participate in the research,
  • Adults protected by law.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (20)

Besancon University Hospital

Besançon, Bourgogne-Franche-Comté, 25000, France

RECRUITING

Brest University Hospital

Brest, Finistère, 29000, France

RECRUITING

Angers University Hospital

Angers, Maine-et-Loire, 49000, France

RECRUITING

Blois Hospital site

Blois, France

NOT YET RECRUITING

Bordeaux University Hospital

Bordeaux, France

NOT YET RECRUITING

Dijon University Hospital

Dijon, France

NOT YET RECRUITING

Grenoble University Hospital

Grenoble, France

NOT YET RECRUITING

CHU de La Rochelle

La Rochelle, France

NOT YET RECRUITING

CH du Mans

Le Mans, France

NOT YET RECRUITING

Léon Site Bérard in Lyon

Lyon, France

NOT YET RECRUITING

Nantes University Hospital

Nantes, France

RECRUITING

Ambroise Paré Hospital - APHP

Paris, France

NOT YET RECRUITING

Avicenne Hospital - APHP

Paris, France

NOT YET RECRUITING

Bichat Hospital - APHP

Paris, France

NOT YET RECRUITING

Saint-Louis Hospital - APHP

Paris, France

NOT YET RECRUITING

CHU de Rennes

Rennes, France

NOT YET RECRUITING

Eugène Marquis site - Rennes

Rennes, France

NOT YET RECRUITING

Rouen University Hospital

Rouen, France

NOT YET RECRUITING

ICO

Saint-Herblain, France

NOT YET RECRUITING

Valence Hospital Site

Valence, France

NOT YET RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples and tumor blocks

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue Diseases

Central Study Contacts

Lise BOUSSEMART, PU-PH

CONTACT

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
OTHER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 20, 2023

First Posted

May 12, 2023

Study Start

July 24, 2023

Primary Completion (Estimated)

July 24, 2028

Study Completion (Estimated)

July 24, 2028

Last Updated

April 15, 2026

Record last verified: 2026-04

Locations