Clinical trial NCT06274541: 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
Official title: Upfront Systematic Tumour BRCA Testing in Patients With High Grade Serous or Endometrioid Ovarian, Fallopian Tube or Primary Peritoneal Cancer: The t-BRCA Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Serous Ovarian Tumor
Endometrioid Carcinoma Ovary
Fallopian Tube Cancer
Primary Peritoneal Carcinoma
Lead sponsor: Cancer Trials Ireland
Sponsor class: NETWORK
First posted: 2024-02-23
Enrollment: 200
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All patients with high grade serous or endometrioid ovarian, fallopian tube or primary peritoneal cancer (HGSEC), either at primary diagnosis or first relapse.

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.

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.

Primary outcomes:
measure: Feasibility of an upfront BRCA1/2 mutation testing pathway in HGSEC in terms of clinicians' experience.
timeFrame: 24 months
measure: Feasibility of an upfront BRCA1/2 mutation testing pathway in HGSEC in terms of patients' experience.
timeFrame: 24 months
measure: The impact on patient management by determining changes in patient treatment (use of a PARP inhibitor or enrolment in BRCA-targeted clinical trials).
timeFrame: 24 months
measure: The impact on patient management by use of clinical genetics counselling sessions.
timeFrame: 24 months
measure: The economic impact of implementing an upfront tumour BRCA1/2 mutation testing pathway in the oncology clinic for HGSEC on the Irish healthcare system, using a health economic analysis (decision analysis model)
timeFrame: 24 months
Secondary outcomes:
measure: The proportion of germline and somatic BRCA1 and BRCA2 mutations among patients with HGSEC in Ireland
timeFrame: 78 months
measure: Patient and disease characteristics (age, stage, degree of surgical cytoreduction, platinum sensitivity) associated with BRCA1/2 mutated HGSEC compared to BRCA1/2 wild type disease.
timeFrame: 78 months
measure: Differences in treatment patterns between BRCA1/2 mutated and BRCA1/2 wild type HGSEC by examining number of systemic therapies used.
timeFrame: 78 months
measure: Differences in treatment patterns between BRCA1/2 mutated and BRCA1/2 wild type HGSEC by examining use of PARP inhibitor therapy.
timeFrame: 78 months
measure: Differences in treatment patterns between BRCA1/2 mutated and BRCA1/2 wild type HGSEC by examining enrolment in clinical trials
timeFrame: 78 months
measure: Identification of clinical outcomes (response platinum free interval (PFI)) associated with BRCA1/2-mutated HGSEC, as compared to BRCA1/2 wild type disease.
timeFrame: 78 months
measure: Identification of clinical outcomes (progression free survival (PFS)) associated with BRCA1/2-mutated HGSEC, as compared to BRCA1/2 wild type disease.
timeFrame: 78 months
measure: Identification of clinical outcomes (overall survival (OS)) associated with BRCA1/2-mutated HGSEC, as compared to BRCA1/2 wild type disease.
timeFrame: 78 months
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital / Mater Private Hospital
state: Leinster
city: Dublin
country: Ireland
facility: St James's Hospital
state: Leinster
city: Cork
country: Ireland
facility: Bon Secours
state: Munster
city: Cork
country: Ireland
facility: Cork University Hospital
state: Munster
city: Limerick
country: Ireland
facility: University Hospital Limerick
state: Munster
Study officials:
affiliation: Beaumont Hospital, Ireland
name: Prof. Bryan Hennessy
role: PRINCIPAL_INVESTIGATOR
References: