Ignite Creation Date:
2024-05-06 @ 3:51 PM
Last Modification Date:
2024-10-26 @ 1:58 PM
Study NCT ID:
NCT04780945
Status:
UNKNOWN
Last Update Posted:
2021-04-01
First Post:
2019-08-27
Brief Title:
Functional Analysis of BRCAness
Sponsor:
Leiden University Medical Center
Organization:
Leiden University Medical Center
Study Overview
Official Title:
Correlation Between Homologous Recombination Deficiency and Response to Olaparib in Patients With Recurrent Epithelial Ovarian Cancer EOC
Status:
UNKNOWN
Status Verified Date:
2021-03
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
FAB
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 ie 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 ie 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None