Ovarian Neoplasm EpithelialPhase 2FABNCT04780945
Functional Analysis of BRCAness
A Phase 2 study testing Functional RAD51 assay and Olaparib Oral Product in people with Ovarian Neoplasm Epithelial and Homologous Recombination Deficiency, run by Leiden University Medical Center at 3 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Neoplasm Epithelial, Homologous Recombination Deficiency, BRCA1 Mutation
- What is being tested?
- Functional RAD51 assay and Olaparib Oral Product
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 3 sitesNetherlands
- Study dates
- 21 Jan 2019to 31 Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
- For inclusion in the optional exploratory genetic research and the optional biomarker research, patients must fulfil informed consent for genetic research and informed consent for biomarker research
Who cannot join
- 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.
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- 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
- Previous allogenic bone marrow transplant or double umbilical cord blood transplantation.
- Patients with myelodysplastic syndrome, acute myeloid leukaemia or with features suggestive of MDS, AML.
- Whole blood transfusions in the last 120 days prior to entry to the study .
- Resting ECG with QTc equal or above 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
Trial locations and contacts
3 sites in 1 country.
Netherlands3 sites
University Medical Center Groningen
Groningen
Leiden University Medical Center
Leiden, 2300RC
Erasmus Medical Center
Rotterdam
About this study
Official title: Correlation Between Homologous Recombination Deficiency and Response to Olaparib in Patients With Recurrent Epithelial Ovarian Cancer (EOC)
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.
Read the detailed description
Epithelial ovarian cancer (EOC) often presents at an advanced stage, and harbours an unfavourable prognosis. Standard of care includes complete or optimal debulking surgery and chemotherapy, however, most patients experience recurrent disease. Recurrences are often treated with additional chemotherapy, and for selected patients, treatment with PARP inhibitors may be an option. Patients with platinum sensitive recurrent epithelial ovarian cancer (EOC) and a germ-line or somatic BRCA1 or BRCA2 mutation, who are in response to platinum based chemotherapy are currently eligible for maintenance treatment with the Poly (ADP-ribose) polymerase (PARP) inhibitor olaparib after chemotherapy. Germline (11-15%) or somatically acquired (6-7%) BRCA1 and BRCA2 mutations lead to deficiency in homologous recombination (HR) and subsequent less effective DNA repair. PARP inhibitors are most effective in HR deficient tumors. There are clear indications that besides BRCA1 or BRCA2 mutated EOC, there is an additional group of EOC (~15-30%) having deficiencies in HR (i.e. BRCAness) that might benefit from treatment with PARP inhibitors (Mukhopadhyay, Cancer Res 2012; Konstantinopolos, Cancer Discovery 2015; Telli, Clin Cancer Res 2016). 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 (Naipal, Clin. Cancer Res., 2014). It is still unknown however, whether the outcome of the RAD51 assay reliably predicts the sensitivity to platinum-based chemotherapy or PARP inhibitors. In the proposed study, we will therefore 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
- Being tested
- Functional RAD51 assay, Olaparib Oral Product
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Functional RAD51 assayDiagnostic test
Also called RECAP assay
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 ProductDrug
Also called Olaparib tablet
300 mg bid
| Study group | Role | What they receive |
|---|---|---|
| Olaparib monotherapy | Experimental | Patients, irrespective of BRCA status, will be treated with olaparib tablet 300 mg bid Receives: Diagnostic Test: Functional RAD51 assay; Drug: Olaparib Oral Product |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 years
Secondary outcomes (5)
Progression free survival (PFS)
time from start of maintenance olaparib to the date of first documented disease progression or death from any cause, whichever occurs first, of olaparib for the BRCA1 or BRCA2 mutant (germline or somatic) HR deficient group, the non BRCA mutant HR deficient group and the HR proficient group
Measured: 3 years
Overall Survival (OS)
time from start olaparib to death (any cause).
Measured: 3 years
RAD51 test
Percentage of informative RAD51 test results in tumor biopsies and/or ascites
Measured: 3 years
Loss of function mutation
Identify loss of function mutations in genes involved in HR as part of the molecular analysis in the HR proficient and HR deficient group as determined by the RAD51 assay.
Measured: 3 years
NCT-CTC toxicity criteria
Safety and adverse events (AE) of Common Terminology Criteria for Adverse Events version 4.03 (CTCAE) grade 3>5.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2021
- Study start21 Jan 2019
- Primary completion31 Dec 2024
- Study completion31 Dec 2024
Why it stopped: recruitment was lower than expected (28/55) due to registration of the IMP in the first and second line treatment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ovarian Neoplasm EpithelialStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- prospective, Dutch, multicenter, single arm phase II study
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Erasmus Medical Center, University Medical Center Groningen
- Responsible party
- Principal investigator, J.R. Kroep, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04780945
- Sponsor's protocol ID
- FAB18
- Acronym
- FAB
- Status last verified
- Feb 2026
- First submitted
- 27 Aug 2019
- Last updated
- 17 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Correlation Between Homologous Recombination Deficiency and Response to Olaparib in Patients With Recurrent Epithelial Ovarian Cancer (EOC)
- ClinicalTrials.gov ID
- NCT04780945
- Acronym / sponsor ID
- FAB / FAB18
- Conditions
- Ovarian Neoplasm Epithelial, Homologous Recombination Deficiency, BRCA1 Mutation, BRCA2 Mutation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: recruitment was lower than expected (28/55) due to registration of the IMP in the first and second line treatment
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- Erasmus Medical Center, University Medical Center Groningen
- Study start
- 21 Jan 2019 (actual)
- Primary completion
- 31 Dec 2024 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 4 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Epithelial ovarian cancer (EOC) often presents at an advanced stage, and harbours an unfavourable prognosis. Standard of care includes complete or optimal debulking surgery and chemotherapy, however, most patients experience recurrent disease. Recurrences are often treated with additional chemotherapy, and for selected patients, treatment with PARP inhibitors may be an option. Patients with platinum sensitive recurrent epithelial ovarian cancer (EOC) and a germ-line or somatic BRCA1 or BRCA2 mutation, who are in response to platinum based chemotherapy are currently eligible for maintenance treatment with the Poly (ADP-ribose) polymerase (PARP) inhibitor olaparib after chemotherapy. Germline (11-15%) or somatically acquired (6-7%) BRCA1 and BRCA2 mutations lead to deficiency in homologous recombination (HR) and subsequent less effective DNA repair. PARP inhibitors are most effective in HR deficient tumors. There are clear indications that besides BRCA1 or BRCA2 mutated EOC, there is an additional group of EOC (~15-30%) having deficiencies in HR (i.e. BRCAness) that might benefit from treatment with PARP inhibitors (Mukhopadhyay, Cancer Res 2012; Konstantinopolos, Cancer Discovery 2015; Telli, Clin Cancer Res 2016). 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 (Naipal, Clin. Cancer Res., 2014). It is still unknown however, whether the outcome of the RAD51 assay reliably predicts the sensitivity to platinum-based chemotherapy or PARP inhibitors. In the proposed study, we will therefore 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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- prospective, Dutch, multicenter, single arm phase II study
| Arm | Type | Receives |
|---|---|---|
| Olaparib monotherapy | Experimental | Diagnostic Test: Functional RAD51 assay, Drug: Olaparib Oral ProductPatients, irrespective of BRCA status, will be treated with olaparib tablet 300 mg bid |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Functional RAD51 assayAlso: RECAP assayex vivo functional assay (RAD51 assay also known as Repair Capacity (RECAP) assay ) to test homologous recombination deficiencie (HRD) in viable tumor tissue | Diagnostic test | Olaparib monotherapy |
| Olaparib Oral ProductAlso: Olaparib tablet300 mg bid | Drug | Olaparib monotherapy |
Primary outcome
Response Rate
Time frame: 3 years
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.
5 secondary outcomes
Progression free survival (PFS)
Time frame: 3 years
Overall Survival (OS)
Time frame: 3 years
RAD51 test
Time frame: 3 years
Loss of function mutation
Time frame: 3 years
NCT-CTC toxicity criteria
Time frame: 3 years
Results and safety
The study was stopped early (reason given: recruitment was lower than expected (28/55) due to registration of the IMP in the first and second line treatment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Functional RAD51 assay and Olaparib Oral Product in people with Ovarian Neoplasm Epithelial and Homologous Recombination Deficiency, run by Leiden University Medical Center at 3 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: recruitment was lower than expected (28/55) due to registration of the IMP in the first and second line treatment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response Rate (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2026.