Predicting the Risk of Ovarian Cancer Recurrence Using Circulating Tumor DNA to Assess Residual Disease

Blood samples and Tumor tissue will be collected at certain timepoints and will be tested.

Study Overview

• Status: Active, not recruiting
• Conditions: Epithelial Ovarian Cancer
• Intervention / Treatment: Diagnostic test: Signatera testing; Diagnostic test: Altera Testing

Detailed Description

Blood samples will be tested by Natera to identify residual tumor DNA for genetic changes in the tumor to potentially improve prediction of long term prognosis and guide treatment options.

• Study Type: Observational
• Enrollment (Estimated): 45

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • AHN West Penn Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Allegheny Health Network Cancer Institute clinics throughout the system

Description

Inclusion Criteria:

Clinical diagnosis of epithelial ovarian cancer stage II-IV

Exclusion Criteria:

Insufficient tumor to perform Signatera testing; Inability to provide consent for the trial

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Females with Stage II-IV epithelial ovarian cancer; All patients, as participation requirements in this study, are required to have blood drawn at the completion of their adjuvant treatment. Blood sample should be collected within 6 weeks of receiving the last cycle of adjuvant chemotherapy. Other optional time points which will be encouraged but not required: After debulking surgery; Serial draws every 3 months while on maintenance or surveillance.

Diagnostic test: Signatera testing; 26mL blood for the first blood draw and tissue sample. 20mL blood all subsequent draws.; Diagnostic test: Altera Testing; 6ml blood and tissue sample.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the effect of a negative Signatera MRD test on progression free survival (PFS) compared to Signatera MRD testing positive patients.	The Signatera MRD test measures the amount of circulating tumor DNA(ctDNA). We seek to assess the effect of a negative versus positive test on PFS. PFS will be measured in months from the time of last platinum adjuvant chemotherapy to objective disease progression on imaging according to RECIST 1.1 or death from any cause	Signatera MRD testing done within 6 weeks of finishing adjuvant therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the effect of the amount of residual tumor after surgery as defined by Signatera MRD testing on length of PFS	We seek to assess if the amount of residual tumor detected on Signatera MRD testing correlates with length of PFS. Similarly, does an undetectable ctDNA level versus detectable level (by Signatera MRD testing) have different lengths of PFS. PFS will be measured in months from the time of last platinum adjuvant chemotherapy to objective disease progression on imaging according to RECIST 1.1 or death from any cause.	Post debulking surgery
To assess the effect of negative Signatera MRD testing on the length of overall survival (OS) as compared to Signatera MRD testing positive patients	This outcomes seeks to assess if a negative Signatera MRD test has a significantly different OS compared to patients with a positive Signatera MRD test. OS will be measured in months from the time of last platinum adjuvant chemotherapy to death from any cause.	Signatera MRD testing done within 6 weeks of finishing adjuvant therapy
To assess the effect of negative Signatera MRD testing on the length of PFS in patients treated with PARP inhibitors (PARPi) compared to Signatera MRD testing positive patients.	We seek to assess the effect of a negative Signatera MRD test on PFS in patients that are treated with PARPi compared to patients with a positive Signatera MRD test. PFS will be measured in months from the time of last platinum adjuvant chemotherapy to objective disease progression on imaging according to RECIST 1.1 or death from any cause.	Signatera MRD testing done within 6 weeks of finishing adjuvant therapy
To assess if recurrent ovarian cancer is detectable earlier by a rise in ctDNA (by Signatera MRD testing) compared to a rise in CA-125.	We seek to assess if Signatera MRD testing will show an increase in ctDNA levels prior to a rise of CA-125 above the normal range.	Patients will be measured by Signatera MRD testing within 6 weeks of completing adjuvant treatment and every 3 months for up to 2 years. CA-125 will be measured every 3 months until progressive disease or death.
To assess if recurrent ovarian cancer is detectable earlier by a rise in ctDNA (by Signatera MRD testing) compared to radiographic method (objective disease progression by RECIST 1.1).	We seek to assess if Signatera MRD testing will show an increase in ctDNA levels prior to objective disease progression by RECIST 1.1	Signatera MRD test within 6 weeks of completing adjuvant treatment and every 3 months for up to 2 years. CT every 3 cycles(1 month cycles) while on maintenance or CT for abnormal CA-125, patient symptom, or clinical exam abnormality on surveillance
To assess if recurrent ovarian cancer is detectable earlier by a rise in ctDNA (by Signatera MRD testing) compared to recurrence as assessed by the investigator.	We seek to assess if Signatera MRD testing will show an increase in ctDNA levels prior to the diagnosis of recurrent disease as assessed by physician evaluation. The physician may use all available clinical information in this determination.	Patients will be measured by Signatera MRD testing within 6 weeks of completing adjuvant treatment and every 3 months for up to 2 years. Physician assessment wil be as per normal surveillance schedule of the investigator.
To assess the effect of maintenance therapy (PARPi or bevacizumab) on the rate of negative Signatera MRD testing as compared to patients not given maintenance therapy.	We seek to assess if patients will be more likely to achieve a negative Signatera MRD test if they are given maintenance therapy as compared to surveillance.	Signatera MRD test within 6 weeks of completing adjuvant treatment and every 3 months for up to 2 years.
We seek to determine if patients assessed with whole exome sequencing (Altera) will show different genetic mutational patterns than those who are Signatera MRD testing positive and negative.	We seek to assess if there are differences in genetic mutations (e.g. BRCA, RAD51, BRIP1, p53, MLH1, PMS2, MSH2 and 6 etc.) between patients that are found to be Signatera MRD testing positive or negative.	Signatera MRD testing done within 6 weeks of finishing adjuvant therapy. Altera testing will be done on the tumor and blood sample provided at enrollment.
We seek to determine if patients assessed with whole exome sequencing (Altera) will show different genetic mutational patterns than those who are PARPi and bevacizumab maintenance therapy responders	We seek to assess if there are differences in genetic mutations (e.g. BRCA, RAD51, BRIP1, p53, MLH1, PMS2, MSH2 and 6 etc.) between patients that are found to be PARPi and bevacizumab maintenance responders	Altera testing will be done on the tumor and blood sample provided at enrollment.
We seek to determine if patients assessed with whole exome sequencing (Altera) will show different genetic mutational patterns when compared by debulking status.	We seek to assess if there are differences in genetic mutations (e.g. BRCA, RAD51, BRIP1, p53, MLH1, PMS2, MSH2 and 6 etc.) between patients whose debulking results in no gross residual disease, optimal debulking or suboptimal debulking	Altera testing will be done on the tumor and blood sample provided at enrollment.

Collaborators and Investigators

• Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
• Investigators: Principal Investigator: John Nakayama, MD, Allegheny Health Network

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2022
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: December 30, 2021
• First Submitted That Met QC Criteria: January 14, 2022
• First Posted (Actual): January 28, 2022

Study Record Updates

• Last Update Posted (Estimated): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Disease Attributes; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Recurrence; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: Signatera

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No