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

Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05458973
• Other study ID #: 4-2017-0851
• Status: Recruiting
• Start date: October 31, 2017
• Est. completion date: October 2024

Study information

• Verified date: September 2022
• Source: Yonsei University
• Contact: Jung-Yun Lee
• Phone: 822-2228-2237
• Email: jungyunlee[@]yuhs.ac
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 19 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Locations

Country	Name	City	State
Korea, Republic of	Yonsei University Health System, Severance Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	every 3 months interval until progression based on clinical surveillance (which usually ranges from 6 months to 2 years)
Secondary	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.	every 3 months interval until progression based on clinical surveillance (which usually ranges from 6 months to 2 years)