Functional Analysis of BRCAness

NCT04780945 | Terminated Phase 2 DMC

• 1 other identifier: FAB18
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Response Rate

  The primary endpoint is the RR, defined as the best overall response (partial response and/or complete response) according to RECIST1.1 for both the HR proficient and HR deficient group as determined by the RAD51 assay.

  3 years

Secondary Outcomes (5)

• Progression free survival (PFS)

  3 years

• Overall Survival (OS)

  3 years

• RAD51 test

  3 years

• Loss of function mutation

  3 years

• NCT-CTC toxicity criteria

  3 years

Other Outcomes (1)

• molecular marker in liquid biopsies

  3 years

Study Arms (1)

Olaparib monotherapy

EXPERIMENTAL

Patients, irrespective of BRCA status, will be treated with olaparib tablet 300 mg bid

Diagnostic Test: Functional RAD51 assay; Drug: Olaparib Oral Product

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

Also known as: RECAP assay

Olaparib monotherapy

Olaparib Oral Product DRUG

300 mg bid

Also known as: Olaparib tablet

Olaparib monotherapy

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with recurrent high grade serous or endometrioid EOC (more than 3 months after platinum containing chemotherapy and unwilling or ineligible for platinum based therapy) with a tumor lesion that is amendable for biopsy or who can undergo ascites drainage prior to treatment.
• Diagnosis of high grade serous or endometrioid EOC confirmed by histology .
• Provision of informed consent prior to any study specific procedures
• Female aged equal or above 18 years
• Patients must have normal organ and bone marrow function measured within 28 days prior to administration olaparib
• Eastern Cooperative Oncology Group performance status 0 to 2
• Patients must have a life expectancy equal or above 16 weeks.
• Postmenopausal or evidence of nonchildbearing status for women of childbearing potential, negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1.
• Patients willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
• Evaluable disease, measurable and, or nonmeasurable, that can be accurately assessed at baseline using RECIST by CT or MRI and is suitable for repeated assessment.

You may not qualify if:

• Participation in another clinical study with an investigational product during the last month.
• Any previous treatment with PARP inhibitor, including olaparib.
• Other malignancy within the last 5 years, except, adequately treated nonmelanoma skin cancer, curatively treated in situ cancer, stage 1 and grade 1 endometrial carcinoma, or other solid tumours including breast cancer and lymphomas curatively treated with no evidence of disease for equal or above 3 years.
• Patients receiving radiotherapy within 3 weeks prior to study treatment.
• Concomitant use of known strong CYP3A inhibitors or moderate CYP3A inhibitors
• Concomitant use of known strong or moderate CYP3A inducers.
• Persistent toxicities , Common Terminology Criteria for Adverse Event equal or above grade 2, caused by previous cancer therapy, excluding alopecia.
• Patients with symptomatic uncontrolled brain metastases. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
• Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active, uncontrolled infection.
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
• Breast feeding women.
• Immunocompromised patients, for example, patients who are known to be serologically positive for human immunodeficiency virus.
• Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
• Patients with known active hepatitis due to risk of transmitting the infection through blood or other body fluids

Sponsors & Collaborators

• Erasmus Medical Center: collaborator
• Leiden University Medical Center: lead
• University Medical Center Groningen: collaborator

Study Sites (3)

University Medical Center Groningen

Groningen, Netherlands

Location

Leiden University Medical Center

Leiden, 2300RC, Netherlands

Location

Erasmus Medical Center

Rotterdam, Netherlands

Location

MeSH Terms

Interventions

olaparib

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD PI

Model Details: prospective, Dutch, multicenter, single arm phase II study

Study Record Dates

• First Submitted: August 27, 2019
• First Posted: March 4, 2021
• Study Start: January 21, 2019
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (3)