Patient case: 64-year-old male with cholangiocarcinoma; genetic feature: BRAF (V600E)

Clinical trial: Follow-up of a National Cohort of Melanoma Stage IV and Unresectable Stage III Patients

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 aiming to validate and identify new prognostic and predictive factors based 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 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 a descriptive and correlative analysis of patients with advanced melanoma in France including epidemiological, clinical and biological socio-economic characteristics
  -  to 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.
  -  to evaluate the risk-benefit, the impact on treatment on patient quality of life, the management cost of patients treated with the validated and future treatments of metastatic melanoma. 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 unresectable stage III or stage IV melanoma will be enrolled prospectively for 1 year with a 5 years follow-up (a total of 2000 patients will be enrolled) from 26 French centers A database of clinical monitoring of metastatic patients will be established and associated with a virtual tumor bank. This national database will be issued from the use of biological, clinical and imaging databases already available in the centers and optimized for this project; this database will also results from the interaction with the French national cancer institute (INCa) genotyping platform.

Detailed description: Melanoma is the first cancer in terms of 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 and anti PD1 antibodies and BRAF and MEK inhibitors .Future improvement of advanced melanoma prognosis will rely on clinico-epidemiological studies and on biological studies aiming to validate and identify new prognostic and predictive factors based 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 in this indication, 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.
  The "Groupe Multidisciplinaire Français du Mélanome cutané" (GMFmel) group plans to build a prospective cohort enrolling advanced melanoma patients, MELBASE. MELBASE is a French national multidisciplinary project whose objectives are :
  -  To provide an annual instrument panel with a descriptive and correlative analysis of patients with advanced melanoma in France including epidemiological, clinical and biological socio-economic characteristics
  -  to 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.
  -  to evaluate the risk-benefit, he impact on treatment on patient quality of life, the management cost of patients treated with the validated and future treatments of metastatic melanoma. If possible, cost-effectiveness ratios wil 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 the populations in which these new therapeutics will be the more 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 unresectable stage III or stage IV melanoma will be enrolled prospectively for 6 years with a 5 years follow-up (a total of 2000 patients will be enrolled) from 26 French centers.
  A database of clinical monitoring of metastatic patients will be established and associated with a virtual tumor bank. The database will be issued from the use of biological, clinical and imaging databases already available in the centers and optimized for this project; this database will also results from the interaction with the INCa genotyping platform. 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, psycho-socio-economic variables including a specific a specific questionnaire, date of death, date of latest news.
  MELBASE will comprise a virtual Tumor bank collecting samples from the same unresectable stage III and stage IV patients enrolled in the study. These samples will be available in the Biological Resource Centers (BRC) of each participating center and will consist of the 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 sampled at inclusion, every 6 months and at each new treatment line during 3 years.
  The computer data processing will therefore ensure the role of a data warehouse to generate clinico-epidemiological reports and analysis and that of a virtual catalog of biological material. MELBASE project will be consistent with the ethical chart of the hospital tumor banks published by Inca and will be managed by a chart ensuring each participating center management autonomy and availability of the data put into the database and made available. A multidisciplinary scientific advisory board will identify research priorities based on clinical practice and scientific knowledge.

Eligibility: Inclusion Criteria:
  -  Patients diagnosed with an advanced melanoma, confirmed by histological exam.
  -  Primitive unresectable stage 3 or 4 melanoma.
  -  Aged > 18 years.
  -  Naïve of systemic treatment for an unresectable stage 3 or 4 melanoma, except adjuvant treatment.
  -  Whose metastatic tumoral material can be collected by the Biological Resource Centers (optional criteria).
  -  Consenting to participate (signed informed consent).
  Exclusion Criteria:
  -  Patients refusal.
  -  Choroid melanoma.
  -  Resectable stage 1, 2 or 3 melanoma.
  -  Patients under guardianship and under trusteeship.

Relevance to patient case: possibly relevant