Circulating Tumor DNA and BRCA Reversion Mutation in Advanced or Recurrent Ovarian Cancer Patients With Germline Mutation.
1 other identifier
observational
100
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for all trials
Started Oct 2017
Longer than P75 for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 31, 2017
CompletedFirst Submitted
Initial submission to the registry
July 5, 2022
CompletedFirst Posted
Study publicly available on registry
July 14, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2024
CompletedSeptember 13, 2022
September 1, 2022
6.9 years
July 5, 2022
September 7, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
identify 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.
every 3 months interval until progression based on clinical surveillance (which usually ranges from 6 months to 2 years)
Secondary Outcomes (2)
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)
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)
Study Arms (2)
Frontline cohort
recurrent cohort
Eligibility Criteria
Ovarian cancer patients with germline BRCA mutation who receive PARP inhibitor
You may qualify if:
- 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.
You may not qualify if:
- Patients who refuse to participate,
- Patients having difficulty understanding the protocol due to language barrier
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Yonsei University Health System, Severance Hospital
Seoul, South Korea
Related Publications (1)
Kim YN, Shim Y, Seo J, Choi Z, Lee YJ, Shin S, Kim SW, Kim S, Choi JR, Lee JY, Lee ST. Investigation of PARP Inhibitor Resistance Based on Serially Collected Circulating Tumor DNA in Patients With BRCA-Mutated Ovarian Cancer. Clin Cancer Res. 2023 Jul 14;29(14):2725-2734. doi: 10.1158/1078-0432.CCR-22-3715.
PMID: 37067525DERIVED
Biospecimen
Circulating tumor DNA based on whole blood. The investigator will peripheral blood from ovarian cancer patients receiving PARP inhibitor for every three months until progression.
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jung-Yun Lee
Severance hospitalYonsei University College of Medicine Department of Obstetrics and Gynecology
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- CASE ONLY
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 5, 2022
First Posted
July 14, 2022
Study Start
October 31, 2017
Primary Completion
October 1, 2024
Study Completion
October 1, 2024
Last Updated
September 13, 2022
Record last verified: 2022-09
Data Sharing
- IPD Sharing
- Will not share