Trial Title:
COsegregation of VARiants in Panel of Genes
NCT ID:
NCT01689584
Condition:
Gene Mutation-Related Cancer
Genetic Predisposition
Conditions: Official terms:
Genetic Predisposition to Disease
Conditions: Keywords:
BRCA1
BRCA2
VUS
co-segregation
genetic counseling
PALB2
panel of genes
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Diagnostic
Masking:
None (Open Label)
Intervention:
Intervention type:
Genetic
Intervention name:
salivary kit
Description:
The saliva samples will be made of selected related (DNA).
Arm group label:
Covar
Summary:
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.
Detailed description:
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.
Criteria for eligibility:
Criteria:
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"
Exclusion Criteria:
- Minors
- Persons deprived of liberty or under guardianship (including curators).
- Absence of signed written inform consent
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Institut Curie - Hopital Rene Huguenin
Address:
City:
Saint-Cloud
Zip:
92210
Country:
France
Status:
Recruiting
Contact:
Last name:
Emmanuelle FOURME, PhD
Email:
emmanuelle.fourme@curie.fr
Investigator:
Last name:
Emmanuelle FOURME, MD
Email:
Principal Investigator
Facility:
Name:
Institut Curie
Address:
City:
Paris
Zip:
75005
Country:
France
Status:
Recruiting
Contact:
Last name:
Sandrine CAPUTO, PhD
Email:
sandrine.caputo@curie.fr
Investigator:
Last name:
Dominique STOPPA-LYONNET, PU-PH
Email:
Principal Investigator
Facility:
Name:
CHU Amiens - Hôpital Nord
Address:
City:
Amiens
Zip:
80054
Country:
France
Status:
Recruiting
Contact:
Last name:
Gilles MORIN, MD
Investigator:
Last name:
Gilles MORIN, MD
Email:
Principal Investigator
Facility:
Name:
ICO - Centre Paul Papin
Address:
City:
Angers
Zip:
49933
Country:
France
Status:
Recruiting
Contact:
Last name:
Marie COUDERT, MD
Investigator:
Last name:
Marie COUDERT, MD
Email:
Principal Investigator
Facility:
Name:
Centre Hospitalier d'Angoulème
Address:
City:
Angoulême
Zip:
16959
Country:
France
Status:
Recruiting
Contact:
Last name:
Stéphanie CHIEZE-VALERO, MD
Investigator:
Last name:
Stéphanie CHIEZE-VALERO, MD
Email:
Principal Investigator
Facility:
Name:
Institut Sainte-Catherine
Address:
City:
Avignon
Zip:
84918
Country:
France
Status:
Recruiting
Contact:
Last name:
Hélène DREYFUS, MD
Investigator:
Last name:
Hélène DREYFUS, MD
Email:
Principal Investigator
Facility:
Name:
CHU Besançon
Address:
City:
Besancon
Zip:
25030
Country:
France
Status:
Recruiting
Contact:
Last name:
Marie-Agnès COLLONGE-RAME, MD
Investigator:
Last name:
Marie-Agnès COLLONGE-RAME, MD
Email:
Principal Investigator
Facility:
Name:
Groupe Hospitalier Pellegrin
Address:
City:
Bordeaux
Zip:
33076
Country:
France
Status:
Recruiting
Contact:
Last name:
Julie TINAT, MD
Investigator:
Last name:
Julie TINAT, MD
Email:
Principal Investigator
Facility:
Name:
Institut Bergonié
Address:
City:
Bordeaux
Zip:
33076
Country:
France
Status:
Recruiting
Contact:
Last name:
Virginie BUBIEN, MD
Investigator:
Last name:
Virginie BUBIEN, MD
Email:
Principal Investigator
Facility:
Name:
Centre Hospitalier Jacques Coeur
Address:
City:
Bourges
Zip:
18020
Country:
France
Status:
Recruiting
Contact:
Last name:
Isabelle MORTEMOUSQUE, MD
Investigator:
Last name:
Isabelle MORTEMOUSQUE, MD
Email:
Principal Investigator
Facility:
Name:
CHU Morvan de Brest
Address:
City:
Brest
Zip:
29200
Country:
France
Status:
Recruiting
Contact:
Last name:
Marc PLANES, MD
Investigator:
Last name:
Marc PLANES, MD
Email:
Principal Investigator
Facility:
Name:
Centre François Baclesse
Address:
City:
Caen
Zip:
14076
Country:
France
Status:
Recruiting
Contact:
Last name:
Pascaline BERTHET, MD
Investigator:
Last name:
Pascaline BERTHET, MD
Email:
Principal Investigator
Facility:
Name:
Centre Hospitalier Hôtel Dieu
Address:
City:
Chambery
Zip:
73011
Country:
France
Status:
Recruiting
Contact:
Last name:
Sandra FERRER, MD
Investigator:
Last name:
Sandra FERRER, MD
Email:
Principal Investigator
Facility:
Name:
Centre Jean Perrin
Address:
City:
Clermont-Ferrand
Zip:
63011
Country:
France
Status:
Recruiting
Contact:
Last name:
Mathilde GAY-BELLILE, MD
Investigator:
Last name:
Mathilde GAY-BELLILE, MD
Email:
Principal Investigator
Facility:
Name:
Hôpital Civil de Colmar
Address:
City:
Colmar
Zip:
68024
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Jean-Marc LIMACHER
Investigator:
Last name:
Jean-Marc LIMACHER, MD
Email:
Principal Investigator
Facility:
Name:
CHU de Dijon
Address:
City:
Dijon
Zip:
21079
Country:
France
Status:
Recruiting
Contact:
Last name:
Laurence FAIVRE-OLIVIER, MD
Investigator:
Last name:
Laurence FAIVRE-OLIVIER, MD
Email:
Principal Investigator
Facility:
Name:
CHU de Grenoble
Address:
City:
Grenoble
Zip:
38043
Country:
France
Status:
Recruiting
Contact:
Last name:
Clémentine LEGRAND, MD
Investigator:
Last name:
Clémentine LEGRAND, MD
Email:
Principal Investigator
Facility:
Name:
Groupe Hospitalier La Rochelle-Ré-Aunis
Address:
City:
La Rochelle
Zip:
17019
Country:
France
Status:
Recruiting
Contact:
Last name:
Stéphanie CHIEZE-VALERO, MD
Investigator:
Last name:
Stéphanie CHIEZE-VALERO, MD
Email:
Principal Investigator
Facility:
Name:
Hôpital Flaubert
Address:
City:
Le Havre
Zip:
76083
Country:
France
Status:
Recruiting
Contact:
Last name:
Elodie LACAZE, MD
Investigator:
Last name:
Elodie LACAZE, MD
Email:
Principal Investigator
Facility:
Name:
Centre Oscar Lambret
Address:
City:
Lille
Zip:
59000
Country:
France
Status:
Recruiting
Contact:
Last name:
Audrey MAILLIEZ, MD
Investigator:
Last name:
Audrey MAILLIEZ, MD
Email:
Principal Investigator
Facility:
Name:
Chru Lille
Address:
City:
Lille
Zip:
59037
Country:
France
Status:
Recruiting
Contact:
Last name:
Sophie LEJEUNE, MD
Investigator:
Last name:
Sophie LEJEUNE, MD
Email:
Principal Investigator
Facility:
Name:
CHU Dupuytren
Address:
City:
Limoges
Zip:
87042
Country:
France
Status:
Recruiting
Contact:
Last name:
Laurence VENAT-BOUVET, MD
Investigator:
Last name:
Laurence VENAT-BOUVET, MD
Email:
Principal Investigator
Facility:
Name:
Hospices Civils de Lyon
Address:
City:
Lyon
Zip:
69229
Country:
France
Status:
Recruiting
Contact:
Last name:
Sophie GIRAUD, MD
Investigator:
Last name:
Sophie GIRAUD, MD
Email:
Principal Investigator
Facility:
Name:
Centre Léon Bérard
Address:
City:
Lyon
Zip:
69373
Country:
France
Status:
Recruiting
Contact:
Last name:
Christine LASSET, MD
Investigator:
Last name:
Christine LASSET, MD
Email:
Principal Investigator
Facility:
Name:
Institut Paoli Calmettes
Address:
City:
Marseille
Zip:
13009
Country:
France
Status:
Recruiting
Contact:
Last name:
Hagay SOBOL, PhD
Investigator:
Last name:
Hagay SOBOL, PhD
Email:
Principal Investigator
Facility:
Name:
CHU La Timone
Address:
City:
Marseille
Zip:
13385
Country:
France
Status:
Recruiting
Contact:
Last name:
Hélène ZATTARA, MD
Investigator:
Last name:
Hélène ZATTARA, MD
Email:
Principal Investigator
Facility:
Name:
CHU Arnaud de Villeneuve
Address:
City:
Montpellier
Zip:
34295
Country:
France
Status:
Recruiting
Contact:
Last name:
Isabelle COUPIER, MD
Investigator:
Last name:
Isabelle COUPIER, MD
Email:
Principal Investigator
Facility:
Name:
Centre Catherine de Sienne
Address:
City:
Nantes
Zip:
44202
Country:
France
Status:
Recruiting
Contact:
Last name:
Alain LORTHOLARY, MD
Investigator:
Last name:
Alain LORTHOLARY, MD
Email:
Principal Investigator
Facility:
Name:
Centre Antoine Lacassagne
Address:
City:
Nice
Zip:
06189
Country:
France
Status:
Recruiting
Contact:
Last name:
Véronique MARI, MD
Investigator:
Last name:
Véronique MARI, MD
Email:
Principal Investigator
Facility:
Name:
Centre Hospitalier Georges Renon
Address:
City:
Niort
Zip:
79021
Country:
France
Status:
Recruiting
Contact:
Last name:
Stéphanie CHIEZE-VALERO, MD
Investigator:
Last name:
Stéphanie CHIEZE-VALERO, MD
Email:
Principal Investigator
Facility:
Name:
CHRU Caremeau
Address:
City:
Nîmes
Zip:
30029
Country:
France
Status:
Recruiting
Contact:
Last name:
Jean CHIESA, MD
Investigator:
Last name:
Jean CHIESA, MD
Email:
Principal Investigator
Facility:
Name:
Hôpital de la Source
Address:
City:
Orléans
Zip:
45067
Country:
France
Status:
Recruiting
Contact:
Last name:
E COTTEREAU, MD
Investigator:
Last name:
E COTTEREAU, MD
Email:
Principal Investigator
Facility:
Name:
Hôpital Saint-Antoine
Address:
City:
Paris
Zip:
75012
Country:
France
Status:
Recruiting
Contact:
Last name:
Antoine DARDENNE, MD
Investigator:
Last name:
Antoine DARDENNE, MD
Email:
Principal Investigator
Facility:
Name:
Groupe Hospitalier Pitié-Salpêtrière
Address:
City:
Paris
Zip:
75013
Country:
France
Status:
Recruiting
Contact:
Last name:
Véronica CUSIN, MD
Investigator:
Last name:
Véronica CUSIN, MD
Email:
Principal Investigator
Facility:
Name:
Hôpital Tenon
Address:
City:
Paris
Zip:
75020
Country:
France
Status:
Recruiting
Contact:
Last name:
Clémence EVREVIN, MD
Investigator:
Last name:
Clémence EVREVIN, MD
Email:
Principal Investigator
Facility:
Name:
Hôpital Saint-Louis
Address:
City:
Paris
Zip:
75475
Country:
France
Status:
Recruiting
Contact:
Last name:
Odile COHEN-HAGUENAUER, MD
Investigator:
Last name:
Odile COHEN-HAGUENAUER, MD
Email:
Principal Investigator
Facility:
Name:
HEGP
Address:
City:
Paris
Zip:
75908
Country:
France
Status:
Recruiting
Contact:
Last name:
Pierre-Laurent PUIG, Phd
Investigator:
Last name:
Pierre-Laurent PUIG, Phd
Email:
Principal Investigator
Facility:
Name:
CHU La Milétrie
Address:
City:
Poitiers
Zip:
86021
Country:
France
Status:
Recruiting
Contact:
Last name:
Stéphanie CHIEZE-VALERO, MD
Investigator:
Last name:
Stéphanie CHIEZE-VALERO, MD
Email:
Principal Investigator
Facility:
Name:
CHU de Reims
Address:
City:
Reims
Zip:
51092
Country:
France
Status:
Recruiting
Contact:
Last name:
Anne DURLACH, MD
Investigator:
Last name:
Anne DURLACH, MD
Email:
Principal Investigator
Facility:
Name:
ICC Courlancy
Address:
City:
Reims
Zip:
51100
Country:
France
Status:
Recruiting
Contact:
Last name:
Fanny BRAYOTEL, MD
Investigator:
Last name:
Fanny BRAYOTEL, MD
Email:
Principal Investigator
Facility:
Name:
Institut Jean Godinot
Address:
City:
Reims
Zip:
51100
Country:
France
Status:
Recruiting
Contact:
Last name:
Tan Dat NGUYEN, PHD
Investigator:
Last name:
Tan Dat NGUYEN, PHD
Email:
Principal Investigator
Facility:
Name:
Centre Eugène Marquis
Address:
City:
Rennes
Zip:
35042
Country:
France
Status:
Recruiting
Contact:
Last name:
Louise CRIVELLI, MD
Investigator:
Last name:
Louise CRIVELLI, MD
Email:
Principal Investigator
Facility:
Name:
CHU de Rouen
Address:
City:
Rouen
Zip:
76031
Country:
France
Status:
Recruiting
Contact:
Last name:
Isabelle TENNEVET, MD
Investigator:
Last name:
Isabelle TENNEVET, MD
Email:
Principal Investigator
Facility:
Name:
ICO - Centre René Gauducheau
Address:
City:
Saint-Herblain
Zip:
44804
Country:
France
Status:
Recruiting
Contact:
Last name:
Capucine DELNATTE, MD
Investigator:
Last name:
Capucine DELNATTE, MD
Email:
Principal Investigator
Facility:
Name:
CHU Saint Etienne
Address:
City:
Saint-Étienne
Zip:
42055
Country:
France
Status:
Recruiting
Contact:
Last name:
Fabienne PRIEUR, MD
Investigator:
Last name:
Fabienne PRIEUR, MD
Email:
Principal Investigator
Facility:
Name:
Institut de Cancérologie Strasbourg Europe ICANS
Address:
City:
Strasbourg
Zip:
67033
Country:
France
Status:
Recruiting
Contact:
Last name:
Philippe BOUDIER, MD
Investigator:
Last name:
Philippe BOUDIER, MD
Email:
Principal Investigator
Facility:
Name:
Hopital de Hautepierre - Hôpital Universitaire
Address:
City:
Strasbourg
Zip:
67200
Country:
France
Status:
Recruiting
Contact:
Last name:
Christine MAUGARD, MD
Investigator:
Last name:
Christine MAUGARD, MD
Email:
Principal Investigator
Facility:
Name:
Institut Claudius Regaud - IUCT - Oncopole
Address:
City:
Toulouse
Zip:
31059
Country:
France
Status:
Recruiting
Contact:
Last name:
Laurence GLADIEFF, MD
Investigator:
Last name:
Laurence GLADIEFF, MD
Email:
Principal Investigator
Facility:
Name:
CHU Bretonneau
Address:
City:
Tours
Zip:
37044
Country:
France
Status:
Recruiting
Contact:
Last name:
Isabelle MORTEMOUSQUE, MD
Investigator:
Last name:
Isabelle MORTEMOUSQUE, MD
Email:
Principal Investigator
Facility:
Name:
CH Simone VEIL
Address:
City:
Troyes
Zip:
10003
Country:
France
Status:
Recruiting
Contact:
Last name:
Charlotte CAILLE-BENIGNI, MD
Investigator:
Last name:
Charlotte CAILLE-BENIGNI, MD
Email:
Principal Investigator
Facility:
Name:
Centre Hospitalier de Valence
Address:
City:
Valence
Zip:
26953
Country:
France
Status:
Recruiting
Contact:
Last name:
Marie-Noëlle BONNET-DUPEYRON, MD
Investigator:
Last name:
Marie-Noëlle BONNET-DUPEYRON, MD
Email:
Principal Investigator
Facility:
Name:
Centre Alexis Vautrin
Address:
City:
Vandoeuvre les Nancy
Zip:
54511
Country:
France
Status:
Withdrawn
Facility:
Name:
CHU Nancy - Hôpital Brabois
Address:
City:
Vandoeuvre les Nancy
Zip:
54511
Country:
France
Status:
Recruiting
Contact:
Last name:
Jean-Marie RAVEL, MD
Investigator:
Last name:
Jean-Marie RAVEL, MD
Email:
Principal Investigator
Facility:
Name:
Gustave Roussy
Address:
City:
Villejuif
Zip:
94805
Country:
France
Status:
Recruiting
Contact:
Last name:
Olivier CARON, MD
Investigator:
Last name:
Olivier CARON, MD
Email:
Principal Investigator
Facility:
Name:
CHU de Pointe à Pitre
Address:
City:
Pointe à Pitre
Zip:
97110
Country:
Guadeloupe
Status:
Recruiting
Contact:
Last name:
Marilyn LACKMY-PORT-LIS, MD
Investigator:
Last name:
Marilyn LACKMY-PORT-LIS, MD
Email:
Principal Investigator
Facility:
Name:
CHU de Fort de France
Address:
City:
Fort de France
Zip:
97261
Country:
Martinique
Status:
Recruiting
Contact:
Last name:
Odile BERA, MD
Investigator:
Last name:
Odile BERA, MD
Email:
Principal Investigator
Facility:
Name:
CHU Sud Réunion Saint-Pierre
Address:
City:
Saint-Pierre
Zip:
97410
Country:
Réunion
Status:
Recruiting
Contact:
Last name:
Hanitra RANJATOELINA, MD
Investigator:
Last name:
Hanitra RANJATOELINA, MD
Email:
Principal Investigator
Start date:
July 2, 2012
Completion date:
January 2, 2034
Lead sponsor:
Agency:
Institut Curie
Agency class:
Other
Source:
Institut Curie
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT01689584
http://www.umd.be/BRCA1/
http://www.umd.be/BRCA2/
