<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01689584</url>
  </required_header>
  <id_info>
    <org_study_id>IC 2011-11</org_study_id>
    <nct_id>NCT01689584</nct_id>
  </id_info>
  <brief_title>COsegregation of VARiants in Panel of Genes</brief_title>
  <acronym>COVAR</acronym>
  <official_title>Study of Family COsegregation of Nucleotide VARiants in the Panel of Genes to Validate Their Use in Genetic Counseling</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut Curie</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institut Curie</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the COVAR project is to classify reliably a maximum of VUS of the French database&#xD;
      in order to use them for the genetic counseling. The results obtained through this study will&#xD;
      have a major impact on clinical management of the patients and their families conducting in&#xD;
      some cases to propose a prophylactic surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Originally, the COVAR study was designed to explore Variants of unknown biological&#xD;
      significance (VUS) in BRCA1 (BReast Cancer 1) and BRCA2 (BReast Cancer 2) genes, which are&#xD;
      the two major genes identified in hereditary breast and/or ovarian cancers. Since then the&#xD;
      study has evolved, in parallel with the evolution of diagnosis, first introducing the PALB2&#xD;
      (Partner and localizer of BRCA2) gene explored in diagnosis since 2015 and now opening the&#xD;
      study to all the genes of the panels performed in diagnosis in families with a genetic&#xD;
      predisposition syndrome to cancers.&#xD;
&#xD;
      The French UMD (Universal Mutation Database)-BRCA1/2, accredited by the French National&#xD;
      Cancer Institute, collects anonymous results of genetic tests performed by authorized French&#xD;
      laboratories since 1995, giving a real-time vision of families carrying the same VUS. In&#xD;
      september 2011, the French UMD-BRCA1/2 database comprised 706 different variants in 1,300&#xD;
      BRCA1 families and 1,089 different variants in 2,101 BRCA2 families. In April 2021, this&#xD;
      database contained 1,651 different VSU for BRCA1, 3,015 different VUS for BRCA2, 471&#xD;
      different VUS for PALB2, 68 for RAD51C and 66 for RAD51D.&#xD;
&#xD;
      Since 2017, new genes have been explored in the diagnostic setting as they have been reported&#xD;
      as predisposing factors for cancers. This list is constantly evolving (Moretta et al., 2018;&#xD;
      Dhooge et al., 2020). Data collection for these genes is ongoing and a new database (FrOG)&#xD;
      gathering all VUS and mutations identified in the French oncogenetic network has been set up.&#xD;
      We have set up a consortium agreement at the end of 2020. This database gathers to date 12&#xD;
      genes and 11,912 different variants in more than 40,000 French families.&#xD;
&#xD;
      One of the key measurable parameters for classification of VUS as causal mutations is their&#xD;
      co-segregation with the disease. The average size of French families is relatively small, the&#xD;
      information of variant co-segregation limited to one family would not be significant.&#xD;
      However, the compilation of co-segregation results obtained from several families will allow&#xD;
      to obtain more precise and complete estimations of the probability of causality of a given&#xD;
      variant.&#xD;
&#xD;
      The objective of the COVAR study (COsegregation VARiants) is to organize co-segregation&#xD;
      studies of the VUS of the database UMD-BRCA1/2, in order to determine the causal or&#xD;
      non-causal nature of these variants. To organize the variants by their clinical relevance, a&#xD;
      grid with 5 classes has been used: 1=neutral, 2=likely neutral, 3=VUS, 4=likely causal,&#xD;
      5=causal. The VUS of classes 3 and 4 will be candidates to co-segregation studies because&#xD;
      they cannot be used for the genetic counseling.&#xD;
&#xD;
      In the selected families the index case will invite the family members (affected and&#xD;
      unaffected) to provide a sample of salivary fluid to test the presence of the VUS. The&#xD;
      probability that a VUS is causal will be calculated from the cosegregation data using a&#xD;
      Bayesian model. The results will be integrated in the multifactorial model described by D.&#xD;
      Goldgar, model integrating different parameters as amino acid conservation, structural impact&#xD;
      of the variant, co-occurrence with a pathogenic mutation, family history and tumor&#xD;
      characteristics.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 2012</start_date>
  <completion_date type="Anticipated">October 2028</completion_date>
  <primary_completion_date type="Anticipated">October 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Perform the co-segregation analysis of the selected VUS in the families in order to classify the maximum of variants in terms of their probability to be pathogenic</measure>
    <time_frame>up to 15 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>• Propose a standardized method to classify VUS that can be integrated into the already existing classification established in the UMD-BRCA1/2 database, with the main focus on variants of class 4 (probably causal) and class 3 (unknown significance).</measure>
    <time_frame>up to 15 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• Maximize the number of VUS (both pathogenic and neutral) having associated recommendations for clinical management of at-risk relatives that can be used to guide genetic counselling.</measure>
    <time_frame>up to 15 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the penetrance of several class 3 and 4 VUS probably associated with moderate cancer risk, using collected phenotype/genotype data on extended pedigrees.</measure>
    <time_frame>up to 15 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">3500</enrollment>
  <condition>Gene Mutation-Related Cancer</condition>
  <condition>Genetic Predisposition</condition>
  <arm_group>
    <arm_group_label>Covar</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>salivary kit</intervention_name>
    <description>The saliva samples will be made of selected related (DNA).</description>
    <arm_group_label>Covar</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Index cases:&#xD;
&#xD;
          -  A person carrying a gene variant class 3 or 4, present and selected in the families of&#xD;
             national database of genetic group and cancer (GGC Unicancer) which identifies the&#xD;
             variations of all genes from the panel of genes of all French laboratories.&#xD;
&#xD;
          -  Age ≥ 18 years.&#xD;
&#xD;
          -  Signed written inform consent &quot;index case&quot;&#xD;
&#xD;
        Related parties:&#xD;
&#xD;
          -  Any relative of an index case with cancer&#xD;
&#xD;
          -  Any relative without cancer related to an index case, retained by investigators, based&#xD;
             on family structure and degree of related compared to the index case&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Information and signature of the informed consent &quot;selected relatives&quot;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Minors&#xD;
&#xD;
          -  Persons deprived of liberty or under guardianship (including curators).&#xD;
&#xD;
          -  Absence of signed written inform consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dominique STOPPA-LYONNET, PU-PH</last_name>
    <role>Study Chair</role>
    <affiliation>Institut Curie</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sandrine CAPUTO, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Institut Curie</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sandrine CAPUTO, PhD</last_name>
    <phone>33172389367</phone>
    <email>sandrine.caputo@curie.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Isabelle TURBIEZ, Project Manager</last_name>
    <phone>33147111659</phone>
    <email>isabelle.turbiez@curie.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Institut Curie - Hopital Rene Huguenin</name>
      <address>
        <city>Saint-Cloud</city>
        <state>Haut De Seine</state>
        <zip>92210</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Emmanuelle FOURME, PhD</last_name>
      <email>emmanuelle.fourme@curie.fr</email>
    </contact>
    <investigator>
      <last_name>Emmanuelle FOURME, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Curie</name>
      <address>
        <city>Paris</city>
        <state>Ile De France</state>
        <zip>75005</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sandrine CAPUTO, PhD</last_name>
      <email>sandrine.caputo@curie.fr</email>
    </contact>
    <investigator>
      <last_name>Dominique STOPPA-LYONNET, PU-PH</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Amiens - Hôpital Nord</name>
      <address>
        <city>Amiens</city>
        <zip>80054</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gilles MORIN, MD</last_name>
    </contact>
    <investigator>
      <last_name>Gilles MORIN, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>ICO - Centre Paul Papin</name>
      <address>
        <city>Angers</city>
        <zip>49933</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Olivier INGSTER, MD</last_name>
    </contact>
    <investigator>
      <last_name>Olivier INGSTER, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier d'Angoulème</name>
      <address>
        <city>Angoulême</city>
        <zip>16959</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paul GESTA, MD</last_name>
    </contact>
    <investigator>
      <last_name>Paul GESTA, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Sainte-Catherine</name>
      <address>
        <city>Avignon</city>
        <zip>84918</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hélène DREYFUS, MD</last_name>
    </contact>
    <investigator>
      <last_name>Hélène DREYFUS, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Besançon</name>
      <address>
        <city>Besancon</city>
        <zip>25030</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marie-Agnès COLLONGE-RAME, MD</last_name>
    </contact>
    <investigator>
      <last_name>Marie-Agnès COLLONGE-RAME, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Groupe Hospitalier Pellegrin</name>
      <address>
        <city>Bordeaux</city>
        <zip>33076</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Julie TINAT, MD</last_name>
    </contact>
    <investigator>
      <last_name>Julie TINAT, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Bergonié</name>
      <address>
        <city>Bordeaux</city>
        <zip>33076</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Virginie BUBIEN, MD</last_name>
    </contact>
    <investigator>
      <last_name>Virginie BUBIEN, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Jacques Coeur</name>
      <address>
        <city>Bourges</city>
        <zip>18020</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Isabelle MORTEMOUSQUE, MD</last_name>
    </contact>
    <investigator>
      <last_name>Isabelle MORTEMOUSQUE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Morvan de Brest</name>
      <address>
        <city>Brest</city>
        <zip>29200</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marc PLANES, MD</last_name>
    </contact>
    <investigator>
      <last_name>Marc PLANES, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre François Baclesse</name>
      <address>
        <city>Caen</city>
        <zip>14076</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pascaline BERTHET, MD</last_name>
    </contact>
    <investigator>
      <last_name>Pascaline BERTHET, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Hôtel Dieu</name>
      <address>
        <city>Chambery</city>
        <zip>73011</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sandra FERRER, MD</last_name>
    </contact>
    <investigator>
      <last_name>Sandra FERRER, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Jean Perrin</name>
      <address>
        <city>Clermont-Ferrand</city>
        <zip>63011</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yves-Jean BIGNON, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Yves-Jean BIGNON, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Civil de Colmar</name>
      <address>
        <city>Colmar</city>
        <zip>68024</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jean-Marc LIMACHER</last_name>
    </contact>
    <investigator>
      <last_name>Jean-Marc LIMACHER, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Dijon</name>
      <address>
        <city>Dijon</city>
        <zip>21079</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Laurence FAIVRE-OLIVIER, MD</last_name>
    </contact>
    <investigator>
      <last_name>Laurence FAIVRE-OLIVIER, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Grenoble</name>
      <address>
        <city>Grenoble</city>
        <zip>38043</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Clémentine LEGRAND, MD</last_name>
    </contact>
    <investigator>
      <last_name>Clémentine LEGRAND, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Groupe Hospitalier La Rochelle-Ré-Aunis</name>
      <address>
        <city>La Rochelle</city>
        <zip>17019</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paul GESTA, MD</last_name>
    </contact>
    <investigator>
      <last_name>Paul GESTA, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Flaubert</name>
      <address>
        <city>Le Havre</city>
        <zip>76083</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elodie LACAZE, MD</last_name>
    </contact>
    <investigator>
      <last_name>Elodie LACAZE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Oscar Lambret</name>
      <address>
        <city>Lille</city>
        <zip>59000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Audrey MAILLIEZ, MD</last_name>
    </contact>
    <investigator>
      <last_name>Audrey MAILLIEZ, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Chru Lille</name>
      <address>
        <city>Lille</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sophie LEJEUNE, MD</last_name>
    </contact>
    <investigator>
      <last_name>Sophie LEJEUNE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Dupuytren</name>
      <address>
        <city>Limoges</city>
        <zip>87042</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Laurence VENAT-BOUVET, MD</last_name>
    </contact>
    <investigator>
      <last_name>Laurence VENAT-BOUVET, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospices Civils de Lyon</name>
      <address>
        <city>Lyon</city>
        <zip>69229</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sophie GIRAUD, MD</last_name>
    </contact>
    <investigator>
      <last_name>Sophie GIRAUD, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Léon Bérard</name>
      <address>
        <city>Lyon</city>
        <zip>69373</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christine LASSET, MD</last_name>
    </contact>
    <investigator>
      <last_name>Christine LASSET, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Paoli Calmettes</name>
      <address>
        <city>Marseille</city>
        <zip>13009</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hagay SOBOL, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Hagay SOBOL, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU La Timone</name>
      <address>
        <city>Marseille</city>
        <zip>13385</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hélène ZATTARA, MD</last_name>
    </contact>
    <investigator>
      <last_name>Hélène ZATTARA, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Arnaud de Villeneuve</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Isabelle COUPIER, MD</last_name>
    </contact>
    <investigator>
      <last_name>Isabelle COUPIER, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Catherine de Sienne</name>
      <address>
        <city>Nantes</city>
        <zip>44202</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alain LORTHOLARY, MD</last_name>
    </contact>
    <investigator>
      <last_name>Alain LORTHOLARY, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Antoine Lacassagne</name>
      <address>
        <city>Nice</city>
        <zip>06189</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Véronique MARI, MD</last_name>
    </contact>
    <investigator>
      <last_name>Véronique MARI, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Georges Renon</name>
      <address>
        <city>Niort</city>
        <zip>79021</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paul GESTA, MD</last_name>
    </contact>
    <investigator>
      <last_name>Paul GESTA, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHRU Caremeau</name>
      <address>
        <city>Nîmes</city>
        <zip>30029</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jean CHIESA, MD</last_name>
    </contact>
    <investigator>
      <last_name>Jean CHIESA, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital de la Source</name>
      <address>
        <city>Orléans</city>
        <zip>45067</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>E COTTEREAU, MD</last_name>
    </contact>
    <investigator>
      <last_name>E COTTEREAU, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint-Antoine</name>
      <address>
        <city>Paris</city>
        <zip>75012</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Antoine DARDENNE, MD</last_name>
    </contact>
    <investigator>
      <last_name>Antoine DARDENNE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Groupe Hospitalier Pitié-Salpêtrière</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Patrick BENUSIGLIO, MD</last_name>
    </contact>
    <investigator>
      <last_name>Patrick BENUSIGLIO, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Tenon</name>
      <address>
        <city>Paris</city>
        <zip>75020</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Patrick BENUSIGLIO, MD</last_name>
    </contact>
    <investigator>
      <last_name>Patrick BENUSIGLIO, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint-Louis</name>
      <address>
        <city>Paris</city>
        <zip>75475</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Odile COHEN-HAGUENAUER, MD</last_name>
    </contact>
    <investigator>
      <last_name>Odile COHEN-HAGUENAUER, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>HEGP</name>
      <address>
        <city>Paris</city>
        <zip>75908</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pierre-Laurent PUIG, Phd</last_name>
    </contact>
    <investigator>
      <last_name>Pierre-Laurent PUIG, Phd</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU La Milétrie</name>
      <address>
        <city>Poitiers</city>
        <zip>86021</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paul GESTA, MD</last_name>
    </contact>
    <investigator>
      <last_name>Paul GESTA, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Reims</name>
      <address>
        <city>Reims</city>
        <zip>51092</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anne DURLACH, MD</last_name>
    </contact>
    <investigator>
      <last_name>Anne DURLACH, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>ICC Courlancy</name>
      <address>
        <city>Reims</city>
        <zip>51100</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fanny BRAYOTEL, MD</last_name>
    </contact>
    <investigator>
      <last_name>Fanny BRAYOTEL, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Jean Godinot</name>
      <address>
        <city>Reims</city>
        <zip>51100</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tan Dat NGUYEN, PHD</last_name>
    </contact>
    <investigator>
      <last_name>Tan Dat NGUYEN, PHD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Eugène Marquis</name>
      <address>
        <city>Rennes</city>
        <zip>35042</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Louise CRIVELLI, MD</last_name>
    </contact>
    <investigator>
      <last_name>Louise CRIVELLI, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Rouen</name>
      <address>
        <city>Rouen</city>
        <zip>76031</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Isabelle TENNEVET, MD</last_name>
    </contact>
    <investigator>
      <last_name>Isabelle TENNEVET, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>ICO - Centre René Gauducheau</name>
      <address>
        <city>Saint-Herblain</city>
        <zip>44804</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Capucine DELNATTE, MD</last_name>
    </contact>
    <investigator>
      <last_name>Capucine DELNATTE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Saint Etienne</name>
      <address>
        <city>Saint-Étienne</city>
        <zip>42055</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fabienne PRIEUR, MD</last_name>
    </contact>
    <investigator>
      <last_name>Fabienne PRIEUR, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut de Cancérologie Strasbourg Europe ICANS</name>
      <address>
        <city>Strasbourg</city>
        <zip>67033</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Cynthia DENIS, MD</last_name>
    </contact>
    <investigator>
      <last_name>Cynthia DENIS, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hopital de Hautepierre - Hôpital Universitaire</name>
      <address>
        <city>Strasbourg</city>
        <zip>67200</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christine MAUGARD, MD</last_name>
    </contact>
    <investigator>
      <last_name>Christine MAUGARD, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Claudius Regaud - IUCT - Oncopole</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Laurence GLADIEFF, MD</last_name>
    </contact>
    <investigator>
      <last_name>Laurence GLADIEFF, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Bretonneau</name>
      <address>
        <city>Tours</city>
        <zip>37044</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Isabelle MORTEMOUSQUE, MD</last_name>
    </contact>
    <investigator>
      <last_name>Isabelle MORTEMOUSQUE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CH Simone VEIL</name>
      <address>
        <city>Troyes</city>
        <zip>10003</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Charlotte CAILLE-BENIGNI, MD</last_name>
    </contact>
    <investigator>
      <last_name>Charlotte CAILLE-BENIGNI, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de Valence</name>
      <address>
        <city>Valence</city>
        <zip>26953</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marie-Noëlle BONNET-DUPEYRON, MD</last_name>
    </contact>
    <investigator>
      <last_name>Marie-Noëlle BONNET-DUPEYRON, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Alexis Vautrin</name>
      <address>
        <city>Vandoeuvre les Nancy</city>
        <zip>54511</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Elisabeth LUPORSI, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Nancy - Hôpital Brabois</name>
      <address>
        <city>Vandoeuvre les Nancy</city>
        <zip>54511</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marie MULLER, MD</last_name>
    </contact>
    <investigator>
      <last_name>Marie MULLER, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Olivier CARON, MD</last_name>
    </contact>
    <investigator>
      <last_name>Olivier CARON, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Pointe à Pitre</name>
      <address>
        <city>Pointe à Pitre</city>
        <zip>97110</zip>
        <country>Guadeloupe</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marilyn LACKMY-PORT-LIS, MD</last_name>
    </contact>
    <investigator>
      <last_name>Marilyn LACKMY-PORT-LIS, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Fort de France</name>
      <address>
        <city>Fort de France</city>
        <zip>97261</zip>
        <country>Martinique</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Odile BERA, MD</last_name>
    </contact>
    <investigator>
      <last_name>Odile BERA, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Sud Réunion Saint-Pierre</name>
      <address>
        <city>Saint-Pierre</city>
        <zip>97410</zip>
        <country>Réunion</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hanitra RANJATOELINA, MD</last_name>
    </contact>
    <investigator>
      <last_name>Hanitra RANJATOELINA, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
    <country>Guadeloupe</country>
    <country>Martinique</country>
    <country>Réunion</country>
  </location_countries>
  <link>
    <url>http://www.umd.be/BRCA1/</url>
    <description>French BRCA1 database</description>
  </link>
  <link>
    <url>http://www.umd.be/BRCA2/</url>
    <description>French BRCA2 database</description>
  </link>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>May 14, 2012</study_first_submitted>
  <study_first_submitted_qc>September 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <last_update_submitted>September 1, 2022</last_update_submitted>
  <last_update_submitted_qc>September 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>BRCA1</keyword>
  <keyword>BRCA2</keyword>
  <keyword>VUS</keyword>
  <keyword>co-segregation</keyword>
  <keyword>genetic counseling</keyword>
  <keyword>PALB2</keyword>
  <keyword>panel of genes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Genetic Predisposition to Disease</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01689584
org study id: IC 2011-11
nct id: NCT01689584
lead sponsor: 
has dmc: No
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.
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Perform the co-segregation analysis of the selected VUS in the families in order to classify the maximum of variants in terms of their probability to be pathogenic
time frame: up to 15 years
measure: • Propose a standardized method to classify VUS that can be integrated into the already existing classification established in the UMD-BRCA1/2 database, with the main focus on variants of class 4 (probably causal) and class 3 (unknown significance).
time frame: up to 15 years
measure: • Maximize the number of VUS (both pathogenic and neutral) having associated recommendations for clinical management of at-risk relatives that can be used to guide genetic counselling.
time frame: up to 15 years
measure: Assess the penetrance of several class 3 and 4 VUS probably associated with moderate cancer risk, using collected phenotype/genotype data on extended pedigrees.
time frame: up to 15 years
arm group label: Covar
arm group type: Other
intervention type: Genetic
intervention name: salivary kit
description: The saliva samples will be made of selected related (DNA).
arm group label: Covar
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dominique STOPPA-LYONNET, PU-PH
role: Study Chair
affiliation: Institut Curie
last name: Sandrine CAPUTO, PhD
role: Study Director
affiliation: Institut Curie
last name: Sandrine CAPUTO, PhD
phone: 33172389367
email: sandrine.caputo@curie.fr
last name: Isabelle TURBIEZ, Project Manager
phone: 33147111659
email: isabelle.turbiez@curie.fr
facility: 
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facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: France
country: Guadeloupe
country: Martinique
country: Réunion
url: http://www.umd.be/BRCA1/
description: French BRCA1 database
url: http://www.umd.be/BRCA2/
description: French BRCA2 database
responsible party type: Sponsor
mesh term: Genetic Predisposition to Disease