Follow-up of a National Cohort of Melanoma Resectable Stage II, Stage III or IV Patients or Unresectable Primary

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Malignant Melanoma

Intervention / Treatment
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* Other: Biological
* Other: Tissular
* Other: Quality of life


Participation Criteria
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Eligibility Criteria
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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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Prospective cohort Resectable stage II or III<br>Patients with resectable stage II or III melanoma | Other: Biological<br>* DNA from peripheral blood mononuclear cells, RNA, plasma, serum sampled at inclusion, every 6 months and before each new systemic therapy.<br>Other: Tissular<br>* 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.<br>Other: Quality of life<br>* Specific questionnaires (FACT-M, EUROQUOL) at inclusion, every 3 months and before each new systemic therapy.<br>|
| Prospective cohort Unresectable stage III or stage IV (resectable or not) or unresectable primary<br>Patients with unresectable stage III, or stage IV (resectable or not) or unresectable primary melanoma | Other: Biological<br>* DNA from peripheral blood mononuclear cells, RNA, plasma, serum sampled at inclusion, every 6 months and before each new systemic therapy.<br>Other: Tissular<br>* 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.<br>Other: Quality of life<br>* Specific questionnaires (FACT-M, EUROQUOL) at inclusion, every 3 months and before each new systemic therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | With a Kaplan-Meier curve analysis and Cox model | 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | With a Kaplan-Meier curve analysis and Cox model | 10 years | 
| Overall response | Determined by tumor assessments | 10 years | 
| Nature and incidence of Treatment-Emergent Adverse Events (Safety) | Evaluated with CTCAE v4.0 or v5.0 | 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melanoma, Skin, Biobank