Follow-up of a National Cohort of Melanoma Stage IV and Unresectable Stage III Patients (MelBase)

• ClinicalTrials.gov Identifier: NCT02828202
• Recruitment Status: Unknown
• First Posted: July 11, 2016
• Last Update Posted: February 15, 2019
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

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 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.

Condition or disease	Intervention/treatment
Malignant Melanoma	Other: Biological; Other: Tissular; Other: Quality of life

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.

Study Design

• Study Type: Observational
• Estimated Enrollment: 2000 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Constitution of a National Cohort of Patients With Metastatic Melanoma Stage IV or Unresectable Stage III With the Objective of Setting up a Epidemiological Monitoring and a Clinico-biological Database, MELBASE
• Actual Study Start Date: February 2013
• Estimated Primary Completion Date: March 2021
• Estimated Study Completion Date: March 2021

Groups and Cohorts

Intervention Details:

• Other: Biological
  DNA from peripheral blood mononuclear cells, RNA, plasma, serum sampled at inclusion, every 6 months and before each new systemic therapy.
• Other: Tissular
  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.
• Other: Quality of life
  Specific questionnaires (FACT-M, EUROQUOL) at inclusion, every 3 months and before each new systemic therapy.

Outcome Measures

Primary Outcome Measures :

1. Overall survival [ Time Frame: 5 years ]
   With a Kaplan-Meier curve analysis and Cox model

Secondary Outcome Measures :

1. Progression-Free Survival (PFS) [ Time Frame: 5 years ]
   With a Kaplan-Meier curve analysis and Cox model
2. Overall response [ Time Frame: 5 years ]
   Determined by tumor assessments
3. Nature and incidence of Treatment-Emergent Adverse Events (Safety) [ Time Frame: 5 years ]
   Evaluated with CTCAE v4.0

Biospecimen Retention:   Samples With DNA

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 and RNA from peripheral blood mononuclear cells, plasma, serum, peripheral blood mononuclear cells sampled at inclusion, every 6 months and before each new systemic therapy during 3 years.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients With Metastatic Melanoma Stage IV or Unresectable Stage III.

Criteria

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.

Contacts and Locations

Contacts

Contact: Celeste Lebbe, MD, PhD; +33142494679; celeste.lebbe@aphp.fr

Contact: Clara Allayous, PhD; +33142499392; clara.allayous@aphp.fr

Locations

France

CHU d'Amiens; Recruiting

Amiens, France

Contact: Catherine Lok, MD, PhD lok.catherine@chu-amiens.fr

Principal Investigator: Catherine Lok, MD, PhD

Sub-Investigator: Jean-Philippe Arnault, MD

Principal Investigator: Gilles Duverlie, MD, PhD

Sub-Investigator: Yves-Edouard Herpe, MD

Sub-Investigator: Henri Sevestre, MD, PhD

CH Annecy Genevois; Recruiting

Annecy, France

Contact: Julie De Quatrebarbes, MD, PhD jdequatrebarbes@ch-annecygenevois.fr

Principal Investigator: Julie De Quatrebarbes, MD, PhD

Sub-Investigator: Anne-Claire Bing, MD

Sub-Investigator: Benedicte Hars, MD

CHU de Besançon; Recruiting

Besançon, France

Contact: François Aubin, MD, PhD francois.aubin@univ-fcomte.fr

Principal Investigator: François Aubin, MD, PhD

Principal Investigator: Severine Valmary-Degano, MD, PhD

Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Avicennes; Recruiting

Bobigny, France, 93000

Contact: Eve Maubec, MD, PhD eve.maubec@aphp.fr

Principal Investigator: Eve Maubec, MD, PhD

Sub-Investigator: Gerome Bohelay, MD

Sub-Investigator: Valentine Heidelberger, MD

Sub-Investigator: Coralie Zumelzu, MD

Principal Investigator: Olivier Schischmanoff, MD, PhD

Principal Investigator: Antoine Martin, MD, PhD

CHU de Bordeaux Hôpital Haut Levêque; Active, not recruiting

Bordeaux, France

CHU de Bordeaux Hôpital Saint-André; Recruiting

Bordeaux, France

Contact: Caroline Dutriaux, MD, PhD caroline.dutriaux@chu-bordeaux.fr

Principal Investigator: Caroline Dutriaux, MD, PhD

Sub-Investigator: Sorilla Prey, MD

Sub-Investigator: H Conte, MD

Sub-Investigator: Emilie Gerard, MD

Principal Investigator: Jean-Philippe Merlio, MD, PhD

Sub-Investigator: Beatrice Vergier, MD, PhD

Sub-Investigator: Pierre Dubus, MD

Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Ambroise Paré; Recruiting

Boulogne-Billancourt, France

Contact: Philippe Saiag, MD, PhD philippe.saiag@aphp.fr

Principal Investigator: Philippe Saiag, MD, PhD

Sub-Investigator: Christine Longvert, MD

Sub-Investigator: Sophie Lipowicz, MD

Sub-Investigator: Amelie Gantzer, MD

Sub-Investigator: Daphne Bosset, MD

Sub-Investigator: Marie-Florence De Maleissye, MD

Sub-Investigator: Adeline Finet, MD

Sub-Investigator: Astrid Blom, MD

Principal Investigator: Jean-Pierre Rabes, MD, PhD

Principal Investigator: Jean-François Emile, MD, PhD

CHU de Brest; Recruiting

Brest, France

Contact: Delphine Legoupil, MD delphine.legoupil@chu-brest.fr

Principal Investigator: Delphine Legoupil, MD

Sub-Investigator: Laurent Misery, MD, PhD

Sub-Investigator: Claire Abasq, MD

Sub-Investigator: Emilie Brenaut, MD

Principal Investigator: Pascale Marcorelles, MD, PhD

Sub-Investigator: Marie-Cecile Nicot, MD

CHU de Caen; Active, not recruiting

Caen, France

CHU de Dijon; Recruiting

Dijon, France

Contact: Sophie Dalac, MD, PhD sophie.dalac@chu-dijon.fr

Principal Investigator: Sophie Dalac, MD, PhD

Sub-Investigator: Pierre Vabres, MD

Sub-Investigator: Evelyne Collet, MD

Sub-Investigator: Geraldine Jeudy, MD

Sub-Investigator: Marie-Helene Aubriot Lorton, MD

Sub-Investigator: Tony Petrella, MD

Sub-Investigator: Bertille Bonniaud, MD

Principal Investigator: Alain Bonnin, MD, PhD

CHU de Grenoble; Recruiting

Grenoble, France

Contact: Marie-Therese Leccia, MD, PhD mtleccia@chu-grenoble.fr

Principal Investigator: Marie-Therese Leccia, MD, PhD

Sub-Investigator: Philippe Lorimier, MD

Principal Investigator: Nicole Pinel, MD, PhD

CHRU de Lille; Recruiting

Lille, France

Contact: Laurent Mortier, MD, PhD laurent.mortier@chru-lille.fr

Principal Investigator: Laurent Mortier, MD, PhD

Sub-Investigator: Anna Greliak, MD

Principal Investigator: Dominique Deplanque, MD, PhD

Principal Investigator: Marie-Christine Copin, MD, PhD

Centre Léon Bérard; Not yet recruiting

Lyon, France

Contact: Eve-Marie Neidhardt, MD, PhD

Principal Investigator: Eve-Marie Neidhardt, MD, PhD

Hospices Civils de Lyon; Recruiting

Lyon, France

Contact: Stephane Dalle, PD, PhD stephane.dalle@chu-lyon.fr

Principal Investigator: Stephane Dalle, MD, PhD

Sub-Investigator: Luc Thomas, MD, PhD

Sub-Investigator: Mona Amini-Adle, MD

Sub-Investigator: Sebastien Debarbieux, MD

Principal Investigator: Alexandra Traverse-Glehen, MD, PhD

Sub-Investigator: Nicole Fabien, MD

Sub-Investigator: Brigitte Balme, MD

Sub-Investigator: Lauriane Depaepe, MD

AP-HM Hopital de la Timone; Recruiting

Marseille, France

Contact: Jean-Jacques Grob, MD, PhD jean-jacques.grob@ap-hm.fr

Principal Investigator: Jean-Jacques Grob, MD, PhD

Sub-Investigator: Caroline Gaudy, MD, PhD

Sub-Investigator: Sandrine Monestier, MD

Sub-Investigator: Sylvie Hesse, MD

Sub-Investigator: Nausicaa Malissen, MD

Principal Investigator: Dominique Figarella-Branger, MD, PhD

CHU de Montpellier; Recruiting

Montpellier, France

Contact: Bernard Guillot, MD, PhD b-guillot@chu-montpellier.fr

Principal Investigator: Bernard Guillot, MD, PhD

Sub-Investigator: Aline Montet, MD

Sub-Investigator: Anne-Sophie Bertrand, MD

Sub-Investigator: Anouck Lamoureux, MD

Principal Investigator: Valerie Costes-Martineau, MD, PhD

Sub-Investigator: Anne-Marie Dupuy, MD

Sub-Investigator: Valerie Rigau, MD

CHU de Nancy; Recruiting

Nancy, France

Contact: Florence Granel-Brocard, MD f.granel-brocard@chu-nancy.fr

Principal Investigator: Florence Granel-Brocard, MD, PhD

Sub-Investigator: Laurent Charbit, MD

Principal Investigator: Jean-Michel Vignaud, MD, PhD

CHU de Nantes; Not yet recruiting

Nantes, France

Contact: Brigitte Dreno, MD, PhD brigitte.dreno@atlanmed.fr

Principal Investigator: Brigitte Dreno, MD, PhD

CHU de Nice; Recruiting

Nice, France

Contact: Jean-Philippe Lacour, MD, PhD lacour@unice.fr

Principal Investigator: Jean-Philippe Lacour, MD, PhD

Principal Investigator: Philippe Bahadoran, MD, PhD

Sub-Investigator: Thierry Passeron, MD, PhD

Sub-Investigator: Henri Montaudie, MD

Sub-Investigator: Florence Le Duff, MD

Sub-Investigator: Marine Cavalie, MD

Sub-Investigator: Alexandra Picard, MD

Sub-Investigator: Feriel Boukari, MD

Principal Investigator: Paul Hofman, MD, PhD

Sub-Investigator: Veronique Hofman, MD

Sub-Investigator: Catherine Butori, MD

CHRU de Nîmes; Recruiting

Nîmes, France

Contact: Pierre-Emmanuel Stoebner, MD, PhD pierre.stoebner@chu-nimes.fr

Principal Investigator: Pierre-Emmanuel Stoebner, MD, PhD

Sub-Investigator: Fanny Fichel, MD

Principal Investigator: Thierry Lavabre-Bertrand, MD, PhD

Sub-Investigator: Jean-Baptiste Gaillard, MD

Sub-Investigator: Pascal Roger, MD, PhD

Assistance Publique - Hôpitaux de Paris (AP-HP), Hopital Saint-Louis, centre d'oncodermatologie; Recruiting

Paris, France

Contact: Celeste Lebbe, MD, PhD celeste.lebbe@aphp.fr

Principal Investigator: Celeste Lebbe, MD, PhD

Sub-Investigator: Jennifer Roux, MD

Sub-Investigator: Barouyr Baroudjian, MD

Sub-Investigator: Pauline Laly, MD

Sub-Investigator: Julie Delyon, MD, PhD

Sub-Investigator: Florian Herms, MD

Principal Investigator: Dominique Vitoux, MD, PhD

Sub-Investigator: Marc Chevrier, MD

Sub-Investigator: Mohamad Hinedi, MD

Principal Investigator: Anne Janin, MD, PhD

Sub-Investigator: Maxime Batistella, MD

Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Bichat; Recruiting

Paris, France

Contact: Vincent Descamps, MD, PhD vincent.descamps@aphp.fr

Principal Investigator: Vincent Descamps, MD, PhD

Sub-Investigator: Beatrice Crickx, MD

Sub-Investigator: Charlotte Fite, MD

Sub-Investigator: Catherine Picard-Dahan, MD, PhD

Sub-Investigator: Valerie Vuong, MD

Sub-Investigator: Florence Brunet-Possenti, MD

Sub-Investigator: Diane Kottler, MD

Principal Investigator: Sarah Tubiana, MD

Principal Investigator: Anne Couvelard, MD, PhD

Sub-Investigator: Lydia Deschamps, MD

Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Cochin; Not yet recruiting

Paris, France

Contact: Marie-Françoise Avril, MD, PhD marie-francoise.avril@aphp.fr

Principal Investigator: Marie-Françoise Avril, MD, PhD

CHU de Rennes; Recruiting

Rennes, France

Contact: Alain Dupuy, MD, PhD alain.dupuy@chu-rennes.fr

Principal Investigator: Alain Dupuy, MD, PhD

Sub-Investigator: Marie-Dominique Galibert, MD

Sub-Investigator: Monica Dinulescu, MD

Sub-Investigator: Cecile Chabbert, MD

Sub-Investigator: Catherine Droitcourt, MD

Sub-Investigator: Henri Adamski, MD

Principal Investigator: Bruno Turlin, MD, PhD

CLCC Eugène Marquis; Recruiting

Rennes, France

Contact: Thierry Lesimple, MD, PhD t.lesimple@rennes.unicancer.fr

Principal Investigator: Thierry Lesimple, MD, PhD

Sub-Investigator: Marc Pracht, MD

Principal Investigator: Bruno Turlin, MD, PhD

CHU de Toulouse; Recruiting

Toulouse, France

Contact: Nicolas Meyer, MD, PhD meyer.n@chu-toulouse.fr

Principal Investigator: Nicolas Meyer, MD, PhD

Sub-Investigator: Sophie Thellier, MD

Sub-Investigator: Marianne Thomas-Pfaab, MD

Sub-Investigator: Cecile Pages Laurent, MD, PhD

Principal Investigator: Pierre Brousset, MD, PhD

Institut Gustave Roussy; Not yet recruiting

Villejuif, France

Contact: Caroline Robert, MD, PhD caroline.robert@gustaveroussy.fr

Principal Investigator: Caroline Robert, MD, PhD

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

National Cancer Institute (NCI)

Investigators

• Study Director: Celeste Lebbe, MD, PhD; Assistance Publique - Hôpitaux de Paris (AP-HP), Hopital Saint-Louis, centre d'oncodermatologie, Paris
• Study Director: Brigitte Dreno, MD, PhD; CHU Nantes

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT02828202
• Other Study ID Numbers: ID-RCB 2015-A00138-41; 2011-244 ( Other Grant/Funding Number: INCa )
• First Posted: July 11, 2016
• Last Update Posted: February 15, 2019
• Last Verified: April 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Melanoma; Skin; Biobank

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas