Circulating Tumor DNA and BRCA Reversion Mutation in Advanced or Recurrent Ovarian Cancer Patients With Germline Mutation.

NCT05458973UNKNOWNOBSERVATIONAL

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.

Key Facts

Lead Sponsor

Yonsei University

Enrollment

100

Start Date

2017-10-31

Completion Date

2024-10-01

Study Type

OBSERVATIONAL

Official Title

Circulating Tumor DNA and BRCA Reversion Mutation in Advanced or Recurrent Ovarian Cancer Patients With Germline Mutation.

Conditions

Ovarian Cancer

Eligibility

Age Range

19 Years – 85 Years

Sex

FEMALE

Inclusion Criteria:

1. Pathological diagnosis of epithelial ovarian cancer,
2. Presence of germline or somatic BRCA mutation,
3. 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,
4. 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.
5. Patients who recurred after 3rd or more lines of chemotherapy and are planned to receive PARP inhibitor.

Exclusion Criteria:

1. Patients who refuse to participate,
2. Patients having difficulty understanding the protocol due to language barrier

Outcome Measures

Primary Outcomes

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.

Time frame: every 3 months interval until progression based on clinical surveillance (which usually ranges from 6 months to 2 years)

Secondary Outcomes

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)

Locations

Yonsei University Health System, Severance Hospital, Seoul, South Korea

Circulating Tumor DNA and BRCA Reversion Mutation in Advanced or Recurrent Ovarian Cancer Patients With Germline Mutation.