<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/NCT03246841</url>
  </required_header>
  <id_info>
    <org_study_id>UC-0104/1605 - TUMOSPEC</org_study_id>
    <secondary_id>2016-A00338-43</secondary_id>
    <secondary_id>ONCO04</secondary_id>
    <nct_id>NCT03246841</nct_id>
  </id_info>
  <brief_title>Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.</brief_title>
  <acronym>TUMOSPEC</acronym>
  <official_title>Investigation of Tumour Spectrum, Penetrance and Clinical Utility of Germline Mutations in New Breast and Ovarian Cancer Susceptibility Genes.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>UNICANCER</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Institut Curie</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Gustave Roussy, Cancer Campus, Grand Paris</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institut National de la Santé Et de la Recherche Médicale, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>UNICANCER</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      TUMOSPEC is a national family study designed to measure the relative and absolute risk of&#xD;
      cancer for carriers of deleterious mutations to these &quot;new&quot; breast cancer (BC) susceptibility&#xD;
      genes. Index cases will be enrolled consecutively from patients attending an appointment at&#xD;
      one of the Unicancer centres, with no other inclusion criteria, and offered a BRCA1/2&#xD;
      analysis as part of their care plan. A panel of 24 TUMOSPEC genes, chosen in advance by a&#xD;
      steering committee, will be tested as the same time as the BRCA1/2 genes, at one of the usual&#xD;
      BRCA1/2 analysis laboratories belonging to the same network and participating in the study.&#xD;
      If a mutation is found, the index cases will be asked to invite their first and second degree&#xD;
      family members and their cousins to take part in the study, regardless of whether they have&#xD;
      cancer. Saliva samples will be then taken and used for a targeted analysis of the familial&#xD;
      abnormality. Each participant will also complete an epidemiological questionnaire in order to&#xD;
      gather information about his/her medical history and any exposure to various risk factors.&#xD;
      All medical and genotype data will be centralised at the Genetic Epidemiology Research&#xD;
      Platform (PIGE, INSERM). The cumulative mutation frequency for all genes is estimated at 10%.&#xD;
      Penetrance will be analysed using methods designed to minimise selection bias. The expression&#xD;
      spectrum of the mutations will also be described. For genes where the number of mutated&#xD;
      families is too low, the data may be contributed to international consortia. The main project&#xD;
      will be preceded by a two-year feasibility study, using the same inclusion criteria and&#xD;
      logistic circuits. It is this pilot study to which the current funding application relates.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 21, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2024</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Penetrance estimation of the mutations identified in the gene panel</measure>
    <time_frame>2 years</time_frame>
    <description>The primary outcome is to obtain unbiased penetrance estimates of the mutations identified in the gene panel (about 20 genes), which will be analysed by the molecular diagnostic laboratories at the same time as the BRCA1 and BRCA2 genes</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The results for the whole panel sequencing will be formatted to be used by all laboratories allowing the subsequent centralisation of the data.</measure>
    <time_frame>2 years</time_frame>
    <description>This outcome will allow to establish a procedure for centralising homogeneous genomic sequencing data produced by the molecular diagnostics laboratories</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relative risk will be determined by the ratio of calculated cancer incidence in mutated and non-mutated families for this gene.</measure>
    <time_frame>2 years</time_frame>
    <description>To determine the deleterious nature of a variant the gene panels will be analysed by the various molecular diagnostics laboratories and we will estimate the relative risk by the ratio of calculated cancer incidence in mutated and non-mutated families for this gene.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">500</enrollment>
  <condition>Hereditary Breast and Ovarian Cancer</condition>
  <condition>Mutation</condition>
  <arm_group>
    <arm_group_label>Analysis of the gene panel</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>The laboratory will carry out the TUMOSPEC gene panel analysis at the same time as the BRCA1 and BRCA2 analysis and will return a negative (no mutation) or positive (presence of a mutation allowing enrolment of family members) result.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Genetic testing</intervention_name>
    <description>A panel of 24 genes, chosen in advance by a steering committee, will be tested as the same time as the BRCA1/2 genes, at one of the usual BRCA1/2 analysis laboratories belonging to the same network and participating in the study.</description>
    <arm_group_label>Analysis of the gene panel</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
        Index case eligibility:&#xD;
&#xD;
        Any person with an indication for a BRCA1/BRCA2 gene analysis and who has been offered&#xD;
        TUMOSPEC panel screening.&#xD;
&#xD;
        Age ≥18 years.&#xD;
&#xD;
        Family member eligibility:&#xD;
&#xD;
        Family members will be eligible if the mutation identified in the Index Case is considered&#xD;
        deleterious.&#xD;
&#xD;
        Any family member to the first and second decree or a cousin of the Index Case. Family&#xD;
        members from both sides of the family will be invited to take part.&#xD;
&#xD;
        Age ≥18 years.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        People deprived of their civil liberties or who are under judicial protection or&#xD;
        guardianship.&#xD;
&#xD;
        Patients unable to answer the questionnaire for social or psychological reasons.&#xD;
&#xD;
        Children of the index cases, of any age.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Olivier CARON, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Gustave Roussy, Villejuif, France</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Andrieu Nadine, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institut Curie, Paris, France</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Severine Eon Marchais, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>PIGE Institut Curie, Paris, France</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jerome LEMONNIER, PhD</last_name>
    <phone>+331 7193 6702</phone>
    <email>j-lemonnier@unicancer.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Gustave Roussy</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Institut Curie - PIGE</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Severine Eon Marchais</last_name>
      <email>Severine.Eon-Marchais@curie.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>August 4, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2017</study_first_posted>
  <last_update_submitted>May 10, 2023</last_update_submitted>
  <last_update_submitted_qc>May 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Oncogeneticists</keyword>
  <keyword>Mutations</keyword>
  <keyword>Breast Cancer</keyword>
  <keyword>Ovarian cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
    <mesh_term>Hereditary Breast and Ovarian Cancer Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.</ipd_time_frame>
    <ipd_access_criteria>The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.</ipd_access_criteria>
  </patient_data>
  <!-- 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/NCT03246841
org study id: UC-0104/1605 - TUMOSPEC
secondary id: 2016-A00338-43
secondary id: ONCO04
nct id: NCT03246841
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
TUMOSPEC is a national family study designed to measure the relative and absolute risk of
      cancer for carriers of deleterious mutations to these "new" breast cancer (BC) susceptibility
      genes. Index cases will be enrolled consecutively from patients attending an appointment at
      one of the Unicancer centres, with no other inclusion criteria, and offered a BRCA1/2
      analysis as part of their care plan. A panel of 24 TUMOSPEC genes, chosen in advance by a
      steering committee, will be tested as the same time as the BRCA1/2 genes, at one of the usual
      BRCA1/2 analysis laboratories belonging to the same network and participating in the study.
      If a mutation is found, the index cases will be asked to invite their first and second degree
      family members and their cousins to take part in the study, regardless of whether they have
      cancer. Saliva samples will be then taken and used for a targeted analysis of the familial
      abnormality. Each participant will also complete an epidemiological questionnaire in order to
      gather information about his/her medical history and any exposure to various risk factors.
      All medical and genotype data will be centralised at the Genetic Epidemiology Research
      Platform (PIGE, INSERM). The cumulative mutation frequency for all genes is estimated at 10%.
      Penetrance will be analysed using methods designed to minimise selection bias. The expression
      spectrum of the mutations will also be described. For genes where the number of mutated
      families is too low, the data may be contributed to international consortia. The main project
      will be preceded by a two-year feasibility study, using the same inclusion criteria and
      logistic circuits. It is this pilot study to which the current funding application relates.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Penetrance estimation of the mutations identified in the gene panel
time frame: 2 years
description: The primary outcome is to obtain unbiased penetrance estimates of the mutations identified in the gene panel (about 20 genes), which will be analysed by the molecular diagnostic laboratories at the same time as the BRCA1 and BRCA2 genes
measure: The results for the whole panel sequencing will be formatted to be used by all laboratories allowing the subsequent centralisation of the data.
time frame: 2 years
description: This outcome will allow to establish a procedure for centralising homogeneous genomic sequencing data produced by the molecular diagnostics laboratories
measure: Relative risk will be determined by the ratio of calculated cancer incidence in mutated and non-mutated families for this gene.
time frame: 2 years
description: To determine the deleterious nature of a variant the gene panels will be analysed by the various molecular diagnostics laboratories and we will estimate the relative risk by the ratio of calculated cancer incidence in mutated and non-mutated families for this gene.
arm group label: Analysis of the gene panel
arm group type: Other
description: The laboratory will carry out the TUMOSPEC gene panel analysis at the same time as the BRCA1 and BRCA2 analysis and will return a negative (no mutation) or positive (presence of a mutation allowing enrolment of family members) result.
intervention type: Other
intervention name: Genetic testing
description: A panel of 24 genes, chosen in advance by a steering committee, will be tested as the same time as the BRCA1/2 genes, at one of the usual BRCA1/2 analysis laboratories belonging to the same network and participating in the study.
arm group label: Analysis of the gene panel
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Olivier CARON, MD
role: Principal Investigator
affiliation: Gustave Roussy, Villejuif, France
last name: Andrieu Nadine, PhD
role: Principal Investigator
affiliation: Institut Curie, Paris, France
last name: Severine Eon Marchais, PhD
role: Principal Investigator
affiliation: PIGE Institut Curie, Paris, France
last name: Jerome LEMONNIER, PhD
phone: +331 7193 6702
email: j-lemonnier@unicancer.fr
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Hereditary Breast and Ovarian Cancer Syndrome
sharing ipd: Yes
ipd description: Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.
ipd access criteria: The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.