Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.

Hereditary Breast and Ovarian Cancer Clinical Trial

— TUMOSPEC  

Official title:

Investigation of Tumour Spectrum, Penetrance and Clinical Utility of Germline Mutations in New Breast and Ovarian Cancer Susceptibility Genes.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03246841
• Other study ID #: UC-0104/1605 - TUMOSPEC
• Secondary ID: 2016-A00338-43ON
• Status: Recruiting
• Phase: N/A
• Start date: September 21, 2017
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2023
• Source: UNICANCER
• Contact: Jerome LEMONNIER, PhD
• Phone: +331 7193 6702
• Email: j-lemonnier[@]unicancer.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: December 31, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion criteria:

Index case eligibility:

Any person with an indication for a BRCA1/BRCA2 gene analysis and who has been offered TUMOSPEC panel screening.

Age =18 years.

Family member eligibility:

Family members will be eligible if the mutation identified in the Index Case is considered deleterious.

Any family member to the first and second decree or a cousin of the Index Case. Family members from both sides of the family will be invited to take part.

Age =18 years.

Exclusion Criteria:

People deprived of their civil liberties or who are under judicial protection or guardianship.

Patients unable to answer the questionnaire for social or psychological reasons.

Children of the index cases, of any age.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Hereditary Breast and Ovarian Cancer
• Hereditary Breast and Ovarian Cancer Syndrome
• Mutation
• Ovarian Neoplasms

Intervention

Other:
• Genetic testing
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.

Locations

Country	Name	City	State
France	Gustave Roussy	Paris
France	Institut Curie - PIGE	Paris

Sponsors (4)

Lead Sponsor	Collaborator
UNICANCER	Gustave Roussy, Cancer Campus, Grand Paris, Institut Curie, Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Penetrance estimation of the mutations identified in the gene panel	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	2 years
Secondary	The results for the whole panel sequencing will be formatted to be used by all laboratories allowing the subsequent centralisation of the data.	This outcome will allow to establish a procedure for centralising homogeneous genomic sequencing data produced by the molecular diagnostics laboratories	2 years
Secondary	Relative risk will be determined by the ratio of calculated cancer incidence in mutated and non-mutated families for this gene.	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.	2 years