EOC: Bespoke ctDNA Assay for Recurrence and Treatment Response Monitoring in Advanced Epithelial Ovarian Cancer

Sponsor

Fudan University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05446545

Collaborator

BGI Tianjin (Industry)

139

Enrollment

Location

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This prospective observational study is to assess the dynamics of circulating tumor DNA (ctDNA) in patients with advanced epithelial ovarian cancer (EOC) undergoing surgery , adjuvant chemotherapy, followed by poly adenosine diphosphate-ribose polymerase (PARP) inhibitors until disease progression or the end of the study. All patients will be closely monitored through out the course of disease by a tumor-informed bespoke ctDNA assay as well as traditional methods of surveillance, such as CA125, HE4, CEA, CA199, and imaging. This study may provide preliminary evidence for ctDNA-guided treatment decisions in future clinical practice.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer	Drug: platinum-sensitive EOC Drug: platinum-resistant and rEOC

Detailed Description

This observational study is designed for exploring prognostic and predictive values of the tumor-informed bespoke ctDNA assay in advanced EOC. Newly diagnosed patients who are eligible for radical surgery or relapsed patients from platinum-based adjuvant chemotherapy who are eligible for secondary cytoreductive surgery will be enrolled. The patients will be treated with SOC adjuvant therapies followed by PARP inhibitor for maintenance.

To evaluate ctDNA dynamics, tumor tissue collected from surgery will be sequenced with whole-exome sequencing (WES) to design patient-specific 16-plex panel. At planned monitoring timepoints, blood samples will be drawn, and ctDNA will be sequenced with ultra-deep ctDNA high-throughput sequencing methods.

Traditional surveillance methods will be applied as comparison, including but not limited to carbohydrate antigen 125 (CA-125)/ human epididymal protein 4 (HE4)/ carcinoembryonic antigen (CEA)/ carbohydrate antigen 199 (CA199), etc., as well as standard imaging.

Survival analyses will be conducted based on ctDNA status (positive/negative) after surgery. Recurrence rate of each subgroup, positive predictive values and negative predictive values etc. will be examined. Changes in ctDNA levels (ΔctDNA) during treatment will be used to evaluate the efficacy of maintenance therapy comparing traditional biomarkers,

Study Design

Study Type:

Observational

Anticipated Enrollment :

139 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Evaluation of Prognostic and Predictive Values of Bespoke Circulating Tumor DNA Assay for Recurrent and Response Monitoring in Patients With Advanced Epithelial Ovarian Cancer

Actual Study Start Date :

Sep 1, 2021

Anticipated Primary Completion Date :

Oct 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
ND-EOC Newly diagnosed patients with advanced EOC who are eligible for radical surgery.	Drug: platinum-sensitive EOC For platinum-sensitive patients: platinum-based combined chemotherapy or bevacizumab will be used for adjuvant treatment, followed by maintenance therapy with poly adenosine diphosphate-ribose polymerase (PARP) inhibitor or bevacizumab
platinum-sensitive rEOC Patients relapsed from platinum-based therapy who are eligible for secondary cytoreductive surgery.	Drug: platinum-resistant and rEOC For platinum-resistant patients or refractory relapsed patients: non-platinum single-drug chemotherapy or combined anti-angiogenic targeted chemotherapy

Arm

Intervention/Treatment

ND-EOC

Newly diagnosed patients with advanced EOC who are eligible for radical surgery.

Drug: platinum-sensitive EOC

For platinum-sensitive patients: platinum-based combined chemotherapy or bevacizumab will be used for adjuvant treatment, followed by maintenance therapy with poly adenosine diphosphate-ribose polymerase (PARP) inhibitor or bevacizumab

platinum-sensitive rEOC

Patients relapsed from platinum-based therapy who are eligible for secondary cytoreductive surgery.

Drug: platinum-resistant and rEOC

For platinum-resistant patients or refractory relapsed patients: non-platinum single-drug chemotherapy or combined anti-angiogenic targeted chemotherapy

Outcome Measures

Primary Outcome Measures

Progression free survival (PFS) [Two years]
Determine PFS in ctDNA positive versus ctDNA negative groups.

Secondary Outcome Measures

Overall Survival (OS) [Two years]
Determine OS in ctDNA positive versus ctDNA negative groups.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Female, over 18 years of age;
Patients with advanced epithelial ovarian cancer who are eligible for radical surgery;
Patients with advanced epithelial ovarian cancer relapsed from platinum-based therapies and eligible for secondary cytoreductive surgery;
The subjects agree to sign the informed consent and agree to use their samples and data for related scientific research;
Subjects agree to collect tissue samples and peripheral blood samples for whole exon sequencing and ctDNA monitoring.

Exclusion Criteria:

Patients who are diagnosed, tested or treated for cancer other than ovarian cancer within 2 years (except for basal skin or squamous cell cancer that has been definitively treated);
Patients in pregnancy;
Patients with a history of blood transfusion within 3 months before enrollment;
Newly diagnosed patients who only received laparoscopic surgery;
Patients received chemotherapy or other anti-tumor therapy before surgery.