Detail Article

Informations générales (source: ClinicalTrials.gov)

Numéro NCT

NCT01689584 En recrutement IDF

Titre

Study of Family COsegregation of Nucleotide VARiants in the Panel of Genes to Validate Their Use in Genetic Counseling (COVAR)

Type

Interventional

Pathologie

Prédisposition génétique à une maladie

Phase

N/A

Promoteur

Institut Curie (Voir sur ClinicalTrials)

Date de début

juillet 2012

Date de fin

janvier 2034

Dernière mise à jour

29 juin 2024

Résumé

The aim of the COVAR project is to classify reliably a maximum of VUS of the French database in order to use them for the genetic counseling. The results obtained through this study will have a major impact on clinical management of the patients and their families conducting in some cases to propose a prophylactic surgery.

Détail

Voir le détail Originally, the COVAR study was designed to explore Variants of unknown biological significance (VUS) in BRCA1 (BReast Cancer 1) and BRCA2 (BReast Cancer 2) genes, which are the two major genes identified in hereditary breast and/or ovarian cancers. Since then the study has evolved, in parallel with the evolution of diagnosis, first introducing the PALB2 (Partner and localizer of BRCA2) gene explored in diagnosis since 2015 and now opening the study to all the genes of the panels performed in diagnosis in families with a genetic predisposition syndrome to cancers. The French UMD (Universal Mutation Database)-BRCA1/2, accredited by the French National Cancer Institute, collects anonymous results of genetic tests performed by authorized French laboratories since 1995, giving a real-time vision of families carrying the same VUS. In september 2011, the French UMD-BRCA1/2 database comprised 706 different variants in 1,300 BRCA1 families and 1,089 different variants in 2,101 BRCA2 families. In April 2021, this database contained 1,651 different VSU for BRCA1, 3,015 different VUS for BRCA2, 471 different VUS for PALB2, 68 for RAD51C and 66 for RAD51D. Since 2017, new genes have been explored in the diagnostic setting as they have been reported as predisposing factors for cancers. This list is constantly evolving (Moretta et al., 2018; Dhooge et al., 2020). Data collection for these genes is ongoing and a new database (FrOG) gathering all VUS and mutations identified in the French oncogenetic network has been set up. We have set up a consortium agreement at the end of 2020. This database gathers to date 12 genes and 11,912 different variants in more than 40,000 French families. One of the key measurable parameters for classification of VUS as causal mutations is their co-segregation with the disease. The average size of French families is relatively small, the information of variant co-segregation limited to one family would not be significant. However, the compilation of co-segregation results obtained from several families will allow to obtain more precise and complete estimations of the probability of causality of a given variant. The objective of the COVAR study (COsegregation VARiants) is to organize co-segregation studies of the VUS of the database UMD-BRCA1/2, in order to determine the causal or non-causal nature of these variants. To organize the variants by their clinical relevance, a grid with 5 classes has been used: 1=neutral, 2=likely neutral, 3=VUS, 4=likely causal, 5=causal. The VUS of classes 3 and 4 will be candidates to co-segregation studies because they cannot be used for the genetic counseling. In the selected families the index case will invite the family members (affected and unaffected) to provide a sample of salivary fluid to test the presence of the VUS. The probability that a VUS is causal will be calculated from the cosegregation data using a Bayesian model. The results will be integrated in the multifactorial model described by D. Goldgar, model integrating different parameters as amino acid conservation, structural impact of the variant, co-occurrence with a pathogenic mutation, family history and tumor characteristics. Fermer le détail

Etablissements

Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données
CLCC INSTITUT CURIE		En recrutement IDF	04/09/2024 13:49:53	Contacter
CLCC RENE HUGUENIN INSTITUT CURIE		En recrutement IDF	04/09/2024 13:49:36	Contacter
Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
AP-HP - Hôpital Saint Antoine	Antoine DARDENNE, MD	En recrutement IDF		Contact (sur clinicalTrials)
AP-HP - Hôpital Tenon	Clémence EVREVIN, MD	En recrutement IDF		Contact (sur clinicalTrials)
CLCC INSTITUT GUSTAVE ROUSSY	Olivier CARON, MD	En recrutement IDF		Contact (sur clinicalTrials)
Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
Centre Alexis Vautrin - 54511 - Vandoeuvre les Nancy - France		Annulé		Contact (sur clinicalTrials)
Centre Antoine Lacassagne - 06189 - Nice - France	Véronique MARI, MD	En recrutement		Contact (sur clinicalTrials)
Centre Catherine de Sienne - 44202 - Nantes - France	Alain LORTHOLARY, MD	En recrutement		Contact (sur clinicalTrials)
Centre Eugène Marquis - 35042 - Rennes - France	Louise CRIVELLI, MD	En recrutement		Contact (sur clinicalTrials)
Centre François Baclesse - 14076 - Caen - France	Pascaline BERTHET, MD	En recrutement		Contact (sur clinicalTrials)
Centre Hospitalier d'Angoulème - 16959 - Angoulême - France	Stéphanie CHIEZE-VALERO, MD	En recrutement		Contact (sur clinicalTrials)
Centre Hospitalier de Valence - 26953 - Valence - France	Marie-Noëlle BONNET-DUPEYRON, MD	En recrutement		Contact (sur clinicalTrials)
Centre Hospitalier Georges Renon - 79021 - Niort - France	Stéphanie CHIEZE-VALERO, MD	En recrutement		Contact (sur clinicalTrials)
Centre Hospitalier Hôtel Dieu - 73011 - Chambery - France	Sandra FERRER, MD	En recrutement		Contact (sur clinicalTrials)
Centre Hospitalier Jacques Coeur - 18020 - Bourges - France	Isabelle MORTEMOUSQUE, MD	En recrutement		Contact (sur clinicalTrials)
Centre Jean Perrin - 63011 - Clermont-Ferrand - France	Mathilde GAY-BELLILE, MD	En recrutement		Contact (sur clinicalTrials)
Centre Léon Bérard - 69373 - Lyon - France	Christine LASSET, MD	En recrutement		Contact (sur clinicalTrials)
Centre Oscar Lambret - 59000 - Lille - France	Audrey MAILLIEZ, MD	En recrutement		Contact (sur clinicalTrials)
CH Simone VEIL - 10003 - Troyes - France	Charlotte CAILLE-BENIGNI, MD	En recrutement		Contact (sur clinicalTrials)
CHRU Caremeau - 30029 - Nîmes - France	Jean CHIESA, MD	En recrutement		Contact (sur clinicalTrials)
Chru Lille - 59037 - Lille - France	Sophie LEJEUNE, MD	En recrutement		Contact (sur clinicalTrials)
CHU Amiens - Hôpital Nord - 80054 - Amiens - France	Gilles MORIN, MD	En recrutement		Contact (sur clinicalTrials)
CHU Arnaud de Villeneuve - 34295 - Montpellier - France	Isabelle COUPIER, MD	En recrutement		Contact (sur clinicalTrials)
CHU Besançon - 25030 - Besancon - France	Marie-Agnès COLLONGE-RAME, MD	En recrutement		Contact (sur clinicalTrials)
CHU Bretonneau - 37044 - Tours - France	Isabelle MORTEMOUSQUE, MD	En recrutement		Contact (sur clinicalTrials)
CHU de Dijon - 21079 - Dijon - France	Laurence FAIVRE-OLIVIER, MD	En recrutement		Contact (sur clinicalTrials)
CHU de Grenoble - 38043 - Grenoble - France	Clémentine LEGRAND, MD	En recrutement		Contact (sur clinicalTrials)
CHU de Reims - 51092 - Reims - France	Anne DURLACH, MD	En recrutement		Contact (sur clinicalTrials)
CHU de Rouen - 76031 - Rouen - France	Isabelle TENNEVET, MD	En recrutement		Contact (sur clinicalTrials)
CHU Dupuytren - 87042 - Limoges - France	Laurence VENAT-BOUVET, MD	En recrutement		Contact (sur clinicalTrials)
CHU La Milétrie - 86021 - Poitiers - France	Stéphanie CHIEZE-VALERO, MD	En recrutement		Contact (sur clinicalTrials)
CHU La Timone - 13385 - Marseille - France	Hélène ZATTARA, MD	En recrutement		Contact (sur clinicalTrials)
CHU Morvan de Brest - 29200 - Brest - France	Marc PLANES, MD	En recrutement		Contact (sur clinicalTrials)
CHU Nancy - Hôpital Brabois - 54511 - Vandoeuvre les Nancy - France	Jean-Marie RAVEL, MD	En recrutement		Contact (sur clinicalTrials)
CHU Saint Etienne - 42055 - Saint-Étienne - France	Fabienne PRIEUR, MD	En recrutement		Contact (sur clinicalTrials)
Groupe Hospitalier La Rochelle-Ré-Aunis - 17019 - La Rochelle - France	Stéphanie CHIEZE-VALERO, MD	En recrutement		Contact (sur clinicalTrials)
Groupe Hospitalier Pellegrin - 33076 - Bordeaux - France	Julie TINAT, MD	En recrutement		Contact (sur clinicalTrials)
Groupe Hospitalier Pitié-Salpêtrière - 75013 - Paris - France	Véronica CUSIN, MD	En recrutement		Contact (sur clinicalTrials)
HEGP - 75908 - Paris - France	Pierre-Laurent PUIG, Phd	En recrutement		Contact (sur clinicalTrials)
Hôpital Civil de Colmar - 68024 - Colmar - France	Jean-Marc LIMACHER	Recrutement non commencé		Contact (sur clinicalTrials)
Hopital de Hautepierre - Hôpital Universitaire - 67200 - Strasbourg - France	Christine MAUGARD, MD	En recrutement		Contact (sur clinicalTrials)
Hôpital de la Source - 45067 - Orléans - France	E COTTEREAU, MD	En recrutement		Contact (sur clinicalTrials)
Hôpital Flaubert - 76083 - Le Havre - France	Elodie LACAZE, MD	En recrutement		Contact (sur clinicalTrials)
Hôpital Saint-Louis - 75475 - Paris - France	Odile COHEN-HAGUENAUER, MD	En recrutement		Contact (sur clinicalTrials)
Hospices Civils de Lyon - 69229 - Lyon - France	Sophie GIRAUD, MD	En recrutement		Contact (sur clinicalTrials)
ICC Courlancy - 51100 - Reims - France	Fanny BRAYOTEL, MD	En recrutement		Contact (sur clinicalTrials)
ICO - Centre Paul Papin - 49933 - Angers - France	Marie COUDERT, MD	En recrutement		Contact (sur clinicalTrials)
ICO - Centre René Gauducheau - 44804 - Saint-Herblain - France	Capucine DELNATTE, MD	En recrutement		Contact (sur clinicalTrials)
Institut Bergonié - 33076 - Bordeaux - France	Virginie BUBIEN, MD	En recrutement		Contact (sur clinicalTrials)
Institut Claudius Regaud - IUCT - Oncopole - 31059 - Toulouse - France	Laurence GLADIEFF, MD	En recrutement		Contact (sur clinicalTrials)
Institut de Cancérologie Strasbourg Europe ICANS - 67033 - Strasbourg - France	Philippe BOUDIER, MD	En recrutement		Contact (sur clinicalTrials)
Institut Jean Godinot - 51100 - Reims - France	Tan Dat NGUYEN, PHD	En recrutement		Contact (sur clinicalTrials)
Institut Paoli Calmettes - 13009 - Marseille - France	Hagay SOBOL, PhD	En recrutement		Contact (sur clinicalTrials)
Institut Sainte-Catherine - 84918 - Avignon - France	Hélène DREYFUS, MD	En recrutement		Contact (sur clinicalTrials)

Critères

Genre

Tous

Nombre d'inclusion

Critère d'inclusion

Inclusion Criteria:

Index cases:

- A person carrying a gene variant class 3 or 4, present and selected in the families
of national database of genetic group and cancer (GGC Unicancer) which identifies
the variations of all genes from the panel of genes of all French laboratories.

- Age ≥ 18 years.

- Signed written inform consent "index case"

Related parties:

- Any relative of an index case with cancer

- Any relative without cancer related to an index case, retained by investigators,
based on family structure and degree of related compared to the index case

- Age ≥ 18 years

- Information and signature of the informed consent "selected relatives"

Critère de non inclusion

- Minors

- Persons deprived of liberty or under guardianship (including curators).

- Absence of signed written inform consent

NCT01689584 - Study of Family COsegregation of Nucleotide VARiants in the Panel of Genes to Validate Their Use in Genetic Counseling (COVAR)

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