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

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 2038

Dernière mise à jour

28 mai 2026

Résumé

The aim of the COVAR project is to achieve reliable classification of as many variants of interest as possible from the French OncoGenetics Database (FrOG, https://frog-db.fr/) 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 investigate 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. Over time, it has evolved alongside advances in genetic diagnostics. First, it incorporated the Partner and Localizer of BRCA2 (PALB2) gene, included in routine testing since 2015, and more recently it has expanded to include all genes analyzed in multigene panels for families suspected of hereditary cancer predisposition syndromes. To support variant interpretation, national databases have been developed. The Universal Mutation DataBase BRCA1/BRCA2 (UMD-BRCA1/BRCA2), maintained within the French oncogenetics network, collects anonymized genetic data and enables the identification of families sharing the same variants. More recently, the FrOG database (established in 2020) has expanded this approach to 38 genes and over 66,000 families, compiling nearly 20,000 distinct variants, including thousands of VUS and likely pathogenic variants. As knowledge has progressed, classification systems have evolved. The term VUS now strictly refers to class 3 variants, while class 4 (likely pathogenic) variants are increasingly actionable in clinical care under certain conditions. Additionally, a subset of class 5 variants with intermediate effects ("hypomorphic" variants) has been recognized, highlighting variability in risk depending on the type of genetic alteration. These variants are now included in COVAR to refine risk estimates. One of the key measurable parameters for classification of variants of interest 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 pathogenicity of a given variant. The main objective of the COVAR study (COsegregation VARiants) is to organize such co-segregation studies using national database data, in order to determine the pathogenicity of selected variants and improve 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 (class 3). 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. For class 4 and hypomorphic class 5 variants, relatives are advised to attend oncogenetic consultations for targeted diagnostic testing without additional sampling. Genetic analyses for class 3 variants are conducted by the identifying laboratory, while classes 4-5 analyses are performed by affiliated GGC laboratories. Results are sent anonymously to the coordinating center for statistical analysis, and only overall variant classification (not individual results) is communicated back. If a variant is found pathogenic, the index case is informed, enabling family communication, possible presymptomatic testing (class 3), and potential clinical management impact (classes 4-5). 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	10/04/2025 13:12:22	Contacter
CLCC RENE HUGUENIN INSTITUT CURIE		En recrutement IDF	10/04/2025 13:12:05	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)
CHI POISSY ST-GERMAIN	Claudia RIZZO, MD			Contact (sur clinicalTrials)
CLCC INSTITUT CURIE	Sandrine CAPUTO, PhD			Contact (sur clinicalTrials)
CLCC INSTITUT GUSTAVE ROUSSY	Olivier CARON, MD	En recrutement IDF		Contact (sur clinicalTrials)
CLCC RENE HUGUENIN INSTITUT CURIE	Emmanuelle FOURME, PhD			Contact (sur clinicalTrials)
IFSI DU GROUPE HOSP. PITIÉ SALPÉTRIÈRE	Véronica CUSIN, MD	En recrutement IDF		Contact (sur clinicalTrials)
Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
Centre Eugène Marquis - 35042 - Rennes - France	Louise CRIVELLI, 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)
CHRU Caremeau - 30029 - Nîmes - France	Jean CHIESA, MD	En recrutement		Contact (sur clinicalTrials)
CHU Amiens - Hôpital Nord - 80054 - Amiens - France	Gilles MORIN, MD	En recrutement		Contact (sur clinicalTrials)
CHU Besançon - 25030 - Besançon - France	Marie-Agnès COLLONGE-RAME, MD			Contact (sur clinicalTrials)
CHU de Grenoble - 38043 - Grenoble - France	Clémentine LEGRAND, MD	En recrutement		Contact (sur clinicalTrials)
CHU La Milétrie - 86021 - Poitiers - France	David TOUGERON, MD	En recrutement		Contact (sur clinicalTrials)
CHU Nancy - Hôpital Brabois - 54511 - Vandœuvre-lès-Nancy - France	Jean-Marie RAVEL, MD			Contact (sur clinicalTrials)
CHU Rennes - Hôpital Sud - 35203 - Rennes - France	Philippe DENIZEAU, MD			Contact (sur clinicalTrials)
Hôpital Civil de Colmar - 68024 - Colmar - France	Jean-Marc LIMACHER	Recrutement non commencé		Contact (sur clinicalTrials)
Hôpital de la Source - 45067 - Orléans - France	Edouard COTTEREAU, MD	En recrutement		Contact (sur clinicalTrials)
Hôpital Flaubert - 76083 - Le Havre - France	Elodie LACAZE, MD	En recrutement		Contact (sur clinicalTrials)
Hospices Civils de Lyon - 69229 - Lyon - France	Stéphane PINSON, 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)
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 - Vandœuvre-lès-Nancy - France				Contact (sur clinicalTrials)
Centre Antoine Lacassagne - 06189 - Nice - France	Véronique MARI, MD	En recrutement		Contact (sur clinicalTrials)
Centre Catherine de Sienne - 44202 - Nantes - France	Cyriac BLONZ, 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 Bastia - 20604 - Bastia - Corsica - France	Franck LE DUFF, MD			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 - Chambéry - France	Sandra FERRER, MD			Contact (sur clinicalTrials)
Centre Hospitalier Jacques Coeur - 18020 - Bourges - France	Isabelle MORTEMOUSQUE, 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)
CHD Vendée - 85925 - La Roche-sur-Yon - France	Céline BIHAN, MD			Contact (sur clinicalTrials)
Chru Lille - 59037 - Lille - France	Sophie LEJEUNE, MD	En recrutement		Contact (sur clinicalTrials)
CHU Arnaud de Villeneuve - 34295 - Montpellier - France	Isabelle COUPIER, 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 Reims - 51092 - Reims - France	Hugo THORN, 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 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 Saint Etienne - 42055 - Saint-Etienne - France	Fabienne PRIEUR, MD			Contact (sur clinicalTrials)
CLCC Paul Strauss - 67033 - Strasbourg - France	Manon CHRETIEN, MD			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)
HEGP - 75908 - Paris - France	Pierre-Laurent PUIG, Phd	En recrutement		Contact (sur clinicalTrials)
Hopital de Hautepierre - Hôpital Universitaire - 67200 - Strasbourg - France	Morgane BOEDEC, MD	En recrutement		Contact (sur clinicalTrials)
Hôpital Saint-Louis - 75475 - Paris - France	Odile COHEN-HAGUENAUER, MD	En recrutement		Contact (sur clinicalTrials)
ICC Courlancy - 51100 - Reims - France	Fanny BRAYOTEL, 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 Jean Godinot - 51100 - Reims - France	Aude-Marie SAVOYE, MD	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

Index cases:

- A person carrying a variant of interest in a gene analyzed in a diagnostic setting
by one of the laboratories within the Genetics and Cancer Group (GGC)-Unicancer
network, classified as class 3, 4 or hypomorphic class 5, and selected by the
national expert group for the gene concerned.

- 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, selected by the investigators,
according to family structure and degree of related compared to the index case

- For class 4 and hypomorphic class 5 variants; relatives currently undergoing
analysis or having already obtained a test result for the variant of interest as
part of clinical care.

- Age ≥ 18 years

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

Exclusion Criteria:

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

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