Functional Analysis of BRCAness

Sponsor
Leiden University Medical Center
Study ID
NCT04780945
Phase
PHASE2
Status
Terminated

Conditions

  • BRCA1 Mutation
  • BRCA2 Mutation
  • Homologous Recombination Deficiency
  • Ovarian Neoplasm Epithelial

Eligibility Criteria

Sex
FEMALE
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Functional RAD51 assay — DIAGNOSTIC_TEST
    ex vivo functional assay (RAD51 assay also known as Repair Capacity (RECAP) assay ) to test homologous recombination deficiencie (HRD) in viable tumor tissue
  • Olaparib Oral Product — DRUG
    300 mg bid

Study Details

PARP inhibitors are most effective in homologous recombinant (HR) deficient tumors. There are clear indications that besides BRCA1 or BRCA2 mutated EOC, there is an additional group of EOC having deficiencies in HR (i.e. BRCAness) that might benefit from treatment with PARP inhibitors. Assessment of HR in high grade EOC might therefore serve as a better predictive biomarker and allow the identification of a larger group of patients that could benefit most from platinum based chemotherapy and maintenance treatment with a PARP inhibitor. We recently developed a robust ex vivo functional assay (RAD51 assay;) to test HR in viable tumor tissue. In the proposed study, we will evaluate whether the RAD51 assay predicts sensitivity to therapy with olaparib, in patients with recurrent EOC. With the RAD51 assay we aim to identify a larger number of patients who will benefit from treatment with the PARP inhibitor olaparib than patients with a germline or somatic BRCA mutation only. Furthermore, we aim to identify molecular markers (including genomic markers) that are associated with the outcome of the RAD51 assay. Finally, we will explore whether these molecular markers can be measured in liquid biopsies by analysing ctDNA.

Key Dates

Start date
Jan 21, 2019
Status verified
Feb 2026
Primary completion
Dec 31, 2024
Completion
Dec 31, 2024

Study Design

Enrollment
27 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC

Arms

  • Experimental: Olaparib monotherapy
    Patients, irrespective of BRCA status, will be treated with olaparib tablet 300 mg bid

Primary Outcome Measure

Response Rate [ Time Frame: 3 years ]

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