Clinical trial NCT02828202: Follow-up of a National Cohort of Melanoma Resectable Stage II, Stage III or IV Patients or Unresectable Primary
Official title: Constitution of a National Cohort of Patients With Metastatic Melanoma Resectable Stage II or Stage III or IV or Unresectable Primary With the Objective of Setting up Epidemiological Monitoring and Clinico-biological Database, MELBASE
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Malignant Melanoma
Keywords: Melanoma
Skin
Biobank
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2016-07-11
Enrollment: 6000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 1. Cohort Patients with Resectable stage II or III melanoma.
2. Cohort Patients With Metastatic Melanoma Stage IV (resectable or not) or Unresectable Stage III or unresectable primary.

Brief summary: Prevention of melanoma can be efficient but mortality remains unchanged and 15 to 20% of patients still die from melanoma. Indeed metastatic melanoma is a heterogeneous highly and multiple mutations driven cancer. Significant survival benefit was demonstrated since 2011 with anti-CTLA4 +/- programmed death-1 (anti PD1) antibodies, B-Raf proto-oncogene, serine/threonine kinase (BRAF) and MAP-ERK kinase (MEK) inhibitors. Future improvement of advanced melanoma prognosis will rely on clinico-epidemiological studies and on biological studies to validate and identify new prognostic and predictive factors based on clinico-epidemiological and histological data, genomic host and tumor alterations, tumor microenvironment characteristics, individual immunological profile and functional imaging. In the context of marketing of costly innovative molecules, prospective collection of economic data on treatment and toxicity are required. Large biobanks collecting data from cohorts of advanced melanoma are mandatory for such projects.

MELBASE is a French prospective national cohort enrolling advanced melanoma patients whose objectives are to :

* provide an annual instrument panel with descriptive and correlative analysis of advanced melanoma patients in France including epidemiological, clinical, biological and economic characteristics
* validate and identify new clinical, epidemiological, and biological prognostic factors such as genomic host and tumor alterations, tumor microenvironment characteristics, individual immunological profile in advanced melanoma
* evaluate the risk-benefit, quality of life, the management cost of patients treated with validated and future treatments. The project also aims to define predictive biomarkers of response and toxicity including pharmacogenetics and tumor genetics alterations, tumor microenvironment characteristics, individual immunological profile.

Patients with resectable stage II or III will be enrolled since June 2023 with a 10 years follow-up.

Patients with unresectable stage III or IV (resectable or not) or unresectable primary melanoma will be enrolled prospectively since March 2013 with a 10 years follow-up (up to 6000 patients) from 27 French centers.

Detailed description: Melanoma is on of rare cancer with increasing frequency in France. Prevention can be efficient in detecting melanoma with good prognosis but mortality remains unchanged and 15 to 20% of patients still die from melanoma. Indeed metastatic melanoma is a heterogeneous highly and multiple mutations driven cancer which is highly resistant to conventional treatments. Significant survival benefit was demonstrated since 2011 with anti-CTLA4 +/- anti PD1 antibodies and BRAF and MEK inhibitors.

In 2019, melanoma treatment with anti-PD1 antibodies or BRAFi+MEKi (dabrafenib+trametinib) was approved in stage III patients. Since 2023, in France, pembrolizumab is also approved for stage IIB/IIC melanoma patients ; thus, adjuvant therapy will be generalized without any sentinel lymph node surgery.

In addition, patients could also be treated by neoadjuvant therapies (pembrolizumab or clinical trial) in case of macroscopique stage III, pauci-metastatic stage IV or in case of rare stage II without surgery.

Future improvement of advanced melanoma prognosis will rely on clinico-epidemiological or biological studies to validate and identify new prognostic and predictive factors, also based on upon clinico-epidemiological and histological data, genomic host and tumor alterations, tumor microenvironment characteristics, individual immunological profile and functional imaging. In the context of marketing of costly innovative molecules, an assessment of resource consumption is required, with prospective collection of economic data on treatment and toxicity. Large biobanks collecting data from cohorts of advanced melanoma are mandatory for such projects.

Thus, MELBASE is a French national clinical biobank whose objectives are to:

* provide an annual instrument panel with descriptive and correlative analysis of advanced melanoma patients in France including epidemiological, clinical, biological and economic characteristics
* validate and identify new clinical, epidemiological, and biological prognostic factors such as genomic host and tumor alterations, tumor microenvironment characteristics, individual immunological profile in advanced melanoma
* evaluate the risk-benefit, quality of life, the management cost of patients treated with validated and future treatments. If possible, cost-effectiveness ratios will be calculated either in all treated patients or in selected populations of patients (based on clinical or biological criteria, like biomarkers), in order to identify populations where these new therapeutics will be the most cost-effective.

The project also aims to define predictive biomarkers of response and toxicity including pharmacogenetics and tumor genetics alterations, tumor microenvironment characteristics, individual immunological profile.

Patients with resectable stage II or III will be enrolled since June 2023 with a 10 years follow-up.

Patients with unresectable stage III or IV (resectable or not) or unresectable primary melanoma will be enrolled prospectively since March 2013 with a 10 years follow-up (up to 6000 patients) from 27 French centers.

The information collected in MELBASE will include clinical constitutional factors, factors linked to primary melanoma, factors linked to previous lymph node involvement, tumor kinetics informations, "American Joint Committee on Cancer" (AJCC) stage at inclusion and after various therapeutic intervention, serological markers, metastatic tumor genotyping (one or more sites, one or more time points), therapeutic interventions (medical, surgical, radiotherapy and palliative strategies) with evaluation of response, tolerance, medical direct costs, impact on quality of life,informations on COVID-19 infection and vaccination, consequences on melanoma treatment, date of death, date of latest news.

A virtual Tumor bank collecting samples (optional) mentions available samples stored each participating centers' Biological Resource Centers (BRC) : primary melanoma (mostly paraffin embedded), metastatic sample (s)(paraffin embedded and frozen) from at least 1 site at inclusion and during evolution (particularly before treatment modification if clinically required), DNA from peripheral blood mononuclear cells, plasma/serum sampled at inclusion, every 6 months and at each new treatment line during 3 years.

All date will be collected and organized on a data warehouse to generate clinico-epidemiological reports, analysis and a virtual catalog of biological material.

MELBASE project is consistent with the ethical chart of the hospital tumor banks published by the national French Cancer Institute (INCa). MelBase will also be managed by a chart ensuring each participating center management autonomy and availability of collected data A multidisciplinary scientific advisory board will identify research priorities based on clinical practice and scientific knowledge.

Eligibility criteria: 1. Cohort Patients with Resectable stage II or III

   Inclusion Criteria:

   Patients diagnosed with resectable stage IIA/IIB/IIC or III melanoma, confirmed by histological exam.

   Naïve of systemic treatment for resectable stage II or III. Whose metastatic tumoral material can be collected by the Biological Resource Centers (optional criteria).

   Aged ≥ 18 years. Consenting to participate (signed informed consent).

   Exclusion Criteria:

   Patients refusal. Choroid melanoma. Resectable stage 1 melanoma. Stage 4, unresectable primitive or unresectable stage 3 melanoma. Patients under guardianship and under trusteeship.
2. Cohort patients with Unresectable stage III or stage IV (resectable or not) or unresectable primary:

Inclusion Criteria:

Patients diagnosed with an advanced melanoma, confirmed by histological exam. Unresectable primitive or unresectable stage III or stage IV (resectable or not) melanoma ; or patients treated by neoadjuvant treatment (exceptional) Naïve of systemic treatment for unresectable primitive or unresectable stage III or stage IV (resectable or not) melanoma, except adjuvant treatment.

Whose metastatic tumoral material can be collected by the Biological Resource Centers (optional criteria).

Aged ≥ 18 years. Consenting to participate (signed informed consent).

Exclusion Criteria:

Resectable stage 1, 2 or 3 melanoma. Patients refusal. Choroid melanoma. Patients under guardianship and under trusteeship.

Primary outcomes:
measure: Overall survival
timeFrame: 10 years
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 10 years
measure: Overall response
timeFrame: 10 years
measure: Nature and incidence of Treatment-Emergent Adverse Events (Safety)
timeFrame: 10 years
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU d'Amiens
city: Annecy
country: France
facility: CH Annecy Genevois
city: Besançon
country: France
facility: CHU de Besançon
city: Bobigny
country: France
facility: Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Avicennes
city: Bordeaux
country: France
facility: CHU de Bordeaux Hôpital Haut Levêque
city: Bordeaux
country: France
facility: CHU de Bordeaux Hôpital Saint-André
city: Boulogne-Billancourt
country: France
facility: Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Ambroise Paré
city: Brest
country: France
facility: CHU de Brest
city: Caen
country: France
facility: CHU de Caen
city: Créteil
country: France
facility: Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Henri Mondor
city: Dijon
country: France
facility: CHU de Dijon
city: Grenoble
country: France
facility: CHU de Grenoble
city: Lille
country: France
facility: CHRU de Lille
city: Lyon
country: France
facility: Centre Léon Bérard
city: Lyon
country: France
facility: Hospices Civils de Lyon
city: Marseille
country: France
facility: AP-HM Hopital de la Timone
city: Montpellier
country: France
facility: CHU de Montpellier
city: Nancy
country: France
facility: CHU de Nancy
city: Nantes
country: France
facility: CHU de Nantes
city: Nice
country: France
facility: CHU de Nice
city: Nîmes
country: France
facility: CHRU de Nîmes
city: Paris
country: France
facility: Assistance Publique - Hôpitaux de Paris (AP-HP), Hopital Saint-Louis, centre d'oncodermatologie
city: Paris
country: France
facility: Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Bichat
city: Paris
country: France
facility: Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Cochin
city: Rennes
country: France
facility: CHU de Rennes
city: Rennes
country: France
facility: CLCC Eugène Marquis
city: Toulouse
country: France
facility: CHU de Toulouse
Study officials:
affiliation: AP-HP, Hopital Saint-Louis, centre d'oncodermatologie, Paris
name: Celeste Lebbe, MD, PhD
role: STUDY_DIRECTOR
affiliation: Nantes University Hospital
name: Gaelle Quereux, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Plaschka M, Benboubker V, Grimont M, Berthet J, Tonon L, Lopez J, Le-Bouar M, Balme B, Tondeur G, de la Fouchardiere A, Larue L, Puisieux A, Grinberg-Bleyer Y, Bendriss-Vermare N, Dubois B, Caux C, Dalle S, Caramel J. ZEB1 transcription factor promotes immune escape in melanoma. J Immunother Cancer. 2022 Mar;10(3):e003484. doi: 10.1136/jitc-2021-003484.