Upfront Systematic Tumour BRCA Testing in Patients With High Grade Serous or Endometrioid Ovarian, Fallopian Tube or Primary Peritoneal Cancer (HGSEC): The t-BRCA Study

NCT ID: NCT06274541

Last Updated: 2024-02-23

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-03-22
• Study Completion Date: 2025-11-30

Brief Summary

A pilot study to evaluate the feasibility of a NGS-based tumour BRCA1/2 mutation testing pathway initiated in the oncology clinic for patients with HGSEC, either at primary diagnosis or first relapse, whereby only patients with a positive germline BRCA1/2 mutation test will be referred to clinical genetics.

Detailed Description

This pilot study will evaluate the feasibility of a NGS-based tumour BRCA1/2 mutation testing pathway initiated in the oncology clinic for patients with HGSEC, either at primary diagnosis or first relapse, whereby only patients with a positive germline BRCA1/2 mutation test will be referred to clinical genetics. Germline BRCA1 and BRCA2 MLPA will be carried out to ensure accurate detection of BRCA1/2 LGRs. Patients with a high clinical risk of being germline mutation carriers and a negative germline BRCA1/2 mutation test should also be referred to clinical genetics. The investigators believe an upfront tumour testing pathway would be more cost-effective, as it would involve testing all patients for tumour BRCA1/2 mutations, followed by a single site germline test to clarify somatic/germline status of this mutation in approximately 25% of patients. In contrast, an upfront germline testing pathway would involve germline BRCA1/2 testing for all patients, followed by tumour BRCA1/2 tests in those 80 - 82% patients who do not have a germline BRCA1/2 mutation.

Systematic testing of patients in the oncology clinic for tumour BRCA1/2 mutations should not only ensure that all patients who are eligible for and agreeable to testing receive it, but also improve the quality of referrals to the clinical genetics team. Moreover, this approach is likely to significantly improve the identification rate of HGSEC patients with germline BRCA1/2 mutations, with resultant benefits for these patients in terms of cancer treatment and prevention, and their families in terms of opportunities for cancer prevention. The identification of patients with BRCA1/2 mutant HGSEC may facilitate treatment with effective maintenance therapies, or participation in clinical trials targeted at patients with BRCA1/2-mutated HGSEC. The incorporation of a health economics analysis relating to the introduction of this proposed testing pathway will further inform on the feasibility of its adoption into routine clinical practice on study completion. Finally, this study will also report on the currently unknown frequency, characteristics, disease course, and treatment patterns of germline and somatic BRCA1/2 mutations in an Irish population with HGSEC.

Conditions

Serous Ovarian Tumor; Endometrioid Carcinoma Ovary; Fallopian Tube Cancer; Primary Peritoneal Carcinoma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients with HGSEC

Somatic and Germline BRCA1/2 Testing

Intervention Type: GENETIC

Germline BRCA1/2 mutation testing will be undertaken by NGS using blood samples. Somatic BRCA1/2 mutation testing will be undertaken by NGS using tumour tissue.

Interventions

Somatic and Germline BRCA1/2 Testing

Germline BRCA1/2 mutation testing will be undertaken by NGS using blood samples. Somatic BRCA1/2 mutation testing will be undertaken by NGS using tumour tissue.

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

1. Patients with high grade serous or high grade endometrioid ovarian, fallopian tube or primary peritoneal carcinoma who:

Are newly diagnosed FIGO stage I - IV or Are currently undergoing primary chemotherapy +/- surgery or Are in remission after completing primary treatment for FIGO stage I - IV disease or Are being planned for, are undergoing or have completed treatment for first relapse

2. Patients with available tumour tissue (archival FFPE surgical resection or tissue/peritoneal biopsy) obtained prior to chemotherapy delivery, for tumour BRCA1/2 testing

3. Patients able to give signed and written informed consent

4. Patients aged 18 years and above

Exclusion Criteria

1. Patients with non-high grade serous or non-high grade endometrioid ovarian, fallopian tube or primary peritoneal carcinoma or unclear histology

2. Patients in second or later relapse of their disease

3. Patients who are known BRCA1 or BRCA2 mutation carriers

4. Patients who have been previously tested for germline BRCA1/2 mutations or have been tested with a hereditary cancer gene panel.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Cancer Trials Ireland

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Prof. Bryan Hennessy

Role: PRINCIPAL_INVESTIGATOR

Beaumont Hospital, Ireland

Locations

Mater Misericordiae University Hospital / Mater Private Hospital

Dublin, Leinster, Ireland

St James's Hospital

Dublin, Leinster, Ireland

Bon Secours

Cork, Munster, Ireland

Cork University Hospital

Cork, Munster, Ireland

University Hospital Limerick

Limerick, Munster, Ireland

Countries

Ireland

Other Identifiers

CTRIAL-IE 18-01

Identifier Type: -

Identifier Source: org_study_id