Circulating Tumor DNA and BRCA Reversion Mutation in Advanced or Recurrent Ovarian Cancer Patients With Germline Mutation.
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Ovarian Cancer
- Sponsor
- Yonsei University
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- identify resistance mechanism after PARPi
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Pathological diagnosis of epithelial ovarian cancer,
- •Presence of germline or somatic BRCA mutation,
- •Patients receiving chemotherapy after primary debulking surgery or interval debulking surgery or patients who are planned to receive chemotherapy after recurrence on first line treatment,
- •Patients with platinum sensitive recurrence (recurrence after 6 months or longer after 1st line treatment) who are planned to receive PARP inhibitor following response to 2nd line chemotherapy.
- •Patients who recurred after 3rd or more lines of chemotherapy and are planned to receive PARP inhibitor.
Exclusion Criteria
- •Patients who refuse to participate,
- •Patients having difficulty understanding the protocol due to language barrier
Outcomes
Primary Outcomes
identify resistance mechanism after PARPi
Time Frame: every 3 months interval until progression based on clinical surveillance (which usually ranges from 6 months to 2 years)
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.
Secondary Outcomes
- Identify post-progression resistance mechanisms that may predict response to subsequent therapy(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(every 3 months interval until progression based on clinical surveillance (which usually ranges from 6 months to 2 years))