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

Recruiting

• Conditions: Ovarian Cancer

• Registration Number: NCT05458973
• Lead Sponsor: Yonsei University

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-10-31
• Study First Submitted: 2022-07-05
• Study First Submitted QC: 2022-07-13
• Study First Posted: 2022-07-14
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-07
• Last Update Posted: 2022-09-13
• Primary Completion: 2024-10
• Study Completion: 2024-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 100

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
identify resistance mechanism after PARPi	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 Outcome Measures

Name	Time	Method
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)	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.
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)	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.

Trial Locations

Locations (1)

Yonsei University Health System, Severance Hospital; 🇰🇷 Seoul, Korea, Republic of