Increasing number of ovarian cancer patients are receiving PARP inhibitor as maintenance or salvage therapy. Predictive factors to PARP inhibitor other than BRCA mutation or HRD status as well as specific resistance mechanism are unknown. Thus, the objective of this study was to prospectively collect serial blood samples in ovarian cancer patients with germline BRCA mutation who receive PARP inhibitor. We investigated circulating tumor DNA (ctDNA) before patients are started on PARP inhibitor and every 3 months thereafter until progression on PARP inhibitor. Through assessment of the changes in ctDNA mutational landscape, we aimed to investigate resistance mechanism to PARP inhibitor including BRCA reversion mutation.
Study Type
OBSERVATIONAL
Enrollment
100
Yonsei University Health System, Severance Hospital
Seoul, South Korea
RECRUITINGidentify resistance mechanism after PARPi
Investigators will utilize baseline and post-progression samples to identify PARP resistance mechanism for each patient. For patients without baseline blood sample prior to PARP inhibitor usage, tumor Next Generation Sequencing results will be utilized. After identification of newly acquired mutations after PARP inhibitor use, these genes then will be classified into resistance mechanism category. Patients will undergo standard clinical surveillance, which will be based on serum CA125 and radiological assessment every 3 months interval; whole blood for ctDNA will also be collected at every 3 months interval. Upon progression based on clinical surveillance (which usually ranges from 6 months to 2 years), the corresponding whole blood-based ctDNA sample can be used as post-progression sample. The post-progression sample can then be compared with the baseline sample to inform PARP resistance mechanism.
Time frame: every 3 months interval until progression based on clinical surveillance (which usually ranges from 6 months to 2 years)
Identify pre-existing genomic profiles that may predict response to PARPi
Investigators will utilize baseline blood samples to identify pre-existing genomic profiles that may predict response to PARPi. Post progression blood samples will be used to identify post-specific mechanisms that may predict response to subsequent therapy.
Time frame: every 3 months interval until progression based on clinical surveillance (which usually ranges from 6 months to 2 years)
Identify post-progression resistance mechanisms that may predict response to subsequent therapy
Investigators will utilize baseline blood samples to identify pre-existing genomic profiles that may predict response to PARPi. Post progression blood samples will be used to identify post-specific mechanisms that may predict response to subsequent therapy. Time frame for measurement of secondary outcome will be the same as the time frame for primary outcome. Clinical profiles such as progression-free survival with respect to PARPi, progression-free survival to post-progression subsequent therapy, and overall survival will be utilized.
Time frame: every 3 months interval until progression based on clinical surveillance (which usually ranges from 6 months to 2 years)
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