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

Malignant Melanoma Clinical Trial

— MelBase  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02828202
• Other study ID #: ID-RCB 2015-A00138-41
• Secondary ID: 2011-244
• Status: Recruiting
• Start date: February 2013
• Est. completion date: March 2024

Study information

• Verified date: March 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Celeste Lebbe, MD, PhD
• Phone: +33142494679
• Email: celeste.lebbe[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6000
• Est. completion date: March 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Malignant Melanoma
• Melanoma

Intervention

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

Locations

Country	Name	City	State
France	CHU d'Amiens	Amiens
France	CH Annecy Genevois	Annecy
France	CHU de Besançon	Besançon
France	Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Avicennes	Bobigny
France	CHU de Bordeaux Hôpital Haut Levêque	Bordeaux
France	CHU de Bordeaux Hôpital Saint-André	Bordeaux
France	Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Ambroise Paré	Boulogne-Billancourt
France	CHU de Brest	Brest
France	CHU de Caen	Caen
France	Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Henri Mondor	Créteil
France	CHU de Dijon	Dijon
France	CHU de Grenoble	Grenoble
France	CHRU de Lille	Lille
France	Centre Léon Bérard	Lyon
France	Hospices Civils de Lyon	Lyon
France	AP-HM Hopital de la Timone	Marseille
France	CHU de Montpellier	Montpellier
France	CHU de Nancy	Nancy
France	CHU de Nantes	Nantes
France	CHU de Nice	Nice
France	CHRU de Nîmes	Nîmes
France	Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Bichat	Paris
France	Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Cochin	Paris
France	Assistance Publique - Hôpitaux de Paris (AP-HP), Hopital Saint-Louis, centre d'oncodermatologie	Paris
France	CHU de Rennes	Rennes
France	CLCC Eugène Marquis	Rennes
France	CHU de Toulouse	Toulouse

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	National Cancer Institute (NCI)

Country where clinical trial is conducted

France, 

Outcome

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

External Links

•   Becquart O. et al., Tolerance and Effectiveness of Targeted Therapies in Aged Patients with Metastatic Melanoma ; Cancers (Basel) . 2021 Jun 18;13(12):3042. doi: 10.3390/cancers13123042.
•   Carlet C. et al., Late-onset adverse events of anti-PD1 therapy in melanoma patients: An observational study from MELBASE, a nationwide prospective cohort; J Am Acad Dermatol . 2022 Feb;86(2):345-352. doi: 10.1016/j.jaad.2021.06.849
•   Casarotto E. et al., Real-world effectiveness of pembrolizumab in advanced melanoma: analysis of a French national clinicobiological database ; Immunotherapy . 2021 Aug;13(11):905-916. doi: 10.2217/imt-2021-0077
•   Di Filippo Y. et al., Relevance of body mass index as a predictor of systemic therapy outcomes in metastatic melanoma: analysis of the MelBase French cohort data; Ann Oncol . 2021 Apr;32(4):542-551. doi: 10.1016/j.annonc.2020.12.012.
•   Girod M. et al., Non-V600E/K BRAF Mutations in Metastatic Melanoma: Molecular Description, Frequency, and Effectiveness of Targeted Therapy in a Large National Cohort ; JCO Precis Oncol . 2022 Nov;6:e2200075. doi: 10.1200/PO.22.00075.
•   Huynh S. et al., Combined Therapy with Anti-PD1 and BRAF and/or MEK Inhibitor for Advanced Melanoma: A Multicenter Cohort Study; Cancers (Basel) . 2020 Jun 23;12(6):1666. doi: 10.3390/cancers12061666
•   Kandel M et al., Quality-of-life assessment in French patients with metastatic melanoma in real life; Cancer . 2020 Feb 1;126(3):611-618. doi: 10.1002/cncr.32554.
•   Kandel M. et al., Cost-Effectiveness Analysis of Sequential Treatment Strategies for Advanced Melanoma in Real Life in France ; Curr Oncol . 2022 Nov 27;29(12):9255-9270. doi: 10.3390/curroncol29120725.
•   Kandel M. et al., Update of survival and cost of metastatic melanoma with new drugs: Estimations from the MelBase cohort ; Eur J Cancer . 2018 Dec;105:33-40. doi: 10.1016/j.ejca.2018.09.026.
•   Placais L. et al.,Risk of irAEs in patients with autoimmune diseases treated by immune checkpoint inhibitors for stage III or IV melanoma: results from a matched case-control study; Ann Rheum Dis 2022 Oct;81(10):1445-1452. doi: 10.1136/ard-2022-222186
•   Rousset P. et al., Impact of systemic therapies in metastatic melanoma of unknown primary: A study from MELBASE, a French multicentric prospective cohort; J Am Acad Dermatol . 2023 Apr;88(4):808-815. doi: 10.1016/j.jaad.2022.11.040
•   Tetu et al.Impact of radiotherapy administered simultaneously with systemic treatment in patients with melanoma brain metastases within MelBase, a French multicentric prospective cohort; Eur J Cancer 2019 May;112:38-46
•   Vallet A. et al., Association of Time From Primary Diagnosis to First Distant Relapse of Metastatic Melanoma With Progression of Disease and Survival ; JAMA Dermatol . 2019 Jun 1;155(6):673-678. doi: 10.1001/jamadermatol.2019.0425.