Circulating Tumour DNA as a Marker of Residual Disease & Response to Adjuvant Chemotherapy in Stage I-IV Ovarian Cancer

Circulating Tumour DNA as a Marker of Residual Disease and Response to Adjuvant Chemotherapy in Stage I-IV Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer (EOC)

To demonstrate that detectable ctDNA in peripheral blood following debulking of the primary tumour or following completion of adjuvant treatment for is associated with subsequent disease recurrence in stage I-IV epithelial, fallopian tube and primary peritoneal cancer (Ovarian Cancer)

Study Overview

• Status: Active, not recruiting
• Conditions: Ovarian Cancer
• Intervention / Treatment: Diagnostic test: Circulating tumour DNA testing

Detailed Description

This is a prospective,multi-centre study involving serial blood collections from 100 stage I-IV debulked (or to be debulked in the case of neoadjuvant chemotherapy) high grade serous, endometrioid and clear cell ovarian, fallopian tube and primary peritoneal cancer patients (EOC) or ovarian carcinosarcoma planned to receive adjuvant chemotherapy. Tumour samples will be made available following patient enrollment for the primary debulking group, and following surgery for the neoadjuvant group for mutation analysis. Ascites will not be accepted. Up to four blood samples in the primary debulking group and up to five blood samples in the neoadjuvant group will be collected from each patient over a 6-8 month period for ctDNA and Ca125 analysis Choice of chemotherapy will be platinum based treatment at the treating clinician's discretion as per standard of care.

• Study Type: Observational
• Enrollment (Actual): 118

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3168
      • Monash Medical Centre
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
    • Melbourne, Victoria, Australia, 3084
      • Mercy Hospital for Women
    • Melbourne, Victoria, Australia, 3002
      • Epworth Freemasons
    • Melbourne, Victoria, Australia, 3021
      • Western Hospital
    • Melbourne, Victoria, Australia, 3144
      • Cabrini Malvern
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • John Hopkins University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients that have had primary debulking surgery for curatively resected stage I-IV high grade serous, endometrioid or clear cell carcinoma, or carcinosarcoma of the ovary, fallopian tube or primary peritoneum. Stage IV patients can only be included in the study if they have had a complete resection of all macroscopic disease with no residual disease.OR Patients commencing neoadjuvant chemotherapy for stage I- III high grade serous, endometrioid or clear cell carcinoma, or carcinosarcoma of the ovary, fallopian tube or primary peritoneum. Women must be planned to undergo interim debulking surgery.

Description

Inclusion Criteria:

1. Patients that have had primary debulking surgery for curatively resected stage I-IV high grade serous, endometrioid or clear cell carcinoma, or carcinosarcoma of the ovary, fallopian tube or primary peritoneum. Stage IV patients can only be included in the study if they have had a complete resection of all macroscopic disease with no residual disease.

   OR Patients commencing neoadjuvant chemotherapy for stage I- III high grade serous, endometrioid or clear cell carcinoma, or carcinosarcoma of the ovary, fallopian tube or primary peritoneum. Women must be planned to undergo interim debulking surgery.

2. A representative tumour sample can be made available for molecular testing after surgery or a core biopsy pre neoadjuvant chemotherapy if available.
3. Fit and planned for adjuvant chemotherapy

Exclusion Criteria:

1. History of another primary cancer within the last 3 years
2. Patients with Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer (EOC) of mucinous subtype and sarcoma
3. Patients with Stage IV disease who have residual disease
4. Patients <18 years

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Circulating DNA in the plasma of cancer patients has been shown to exhibit tumour-related alteration. These mutations in tumour cells,can be used as highly specific biomarkers of disease burden. Baseline.	polymerase chain reaction (PCR) to quantify ctDNA	After surgery (primary debulking group) or pre cycle 1 of therapy (neoadjuvant) confirmed with conventional radiological imaging and CA125 (cycles of chemotherapy are 21 days in length).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Circulating DNA in the plasma of cancer patients has been shown to exhibit tumour-related alteration. These mutations in tumour cells can be used as highly specific biomarkers of disease burden. Change from baseline and previous result.	polymerase chain reaction (PCR) to quantify ctDNA	At the completion of pre cycle 3 of chemotherapy (primary debulking group) confirmed with Convential Radiological imaging and CA125. (each cycle 21 days in length)
Circulating DNA in the plasma of cancer patients has been shown to exhibit tumour-related alteration. These mutations in tumour cells can be used as highly specific biomarkers of disease burden. Change from baseline and previous result.	polymerase chain reaction (PCR) to quantify ctDNA	circulating tumour DNA (ctDNA) during chemotherapy pre cycle 5 confirmed (primary debluking group) with conventional Radiological imaging and CA125 (each cycle 21 days in length).
Circulating DNA in the plasma of cancer patients has been shown to exhibit tumour-related alteration. These mutations in tumour cells can be used as highly specific biomarkers of disease burden. Change from baseline and previous result	polymerase chain reaction (PCR) to quantify ctDNA	circulating tumour DNA (ctDNA) during chemotherapy pre cycle 3 or 4 (neoadjuvant group) confirmed with conventional Radiological imaging and CA125 (each cycle 21 days in length)
Circulating DNA in the plasma of cancer patients has been shown to exhibit tumour-related alteration. These mutations in tumour cells can be used as highly specific biomarkers of disease burden. Change from baseline and previous result.	polymerase chain reaction (PCR) to quantify ctDNA	At the completion of 6 of chemotherapy (primary debulking group) confirmed with conventional Radiological imaging and CA125 (each cycle 21 days in length)
Circulating DNA in the plasma of cancer patients has been shown to exhibit tumour-related alteration. These mutations in tumour cells can be used as highly specific biomarkers of disease burden. Change from baseline and previous result.	polymerase chain reaction (PCR) to quantify ctDNA	At the completion of 6 cycles of chemotherapy (neoadjuvant group) confirmed with conventional radiology and CA125 (at the end of 18 weeks).

Collaborators and Investigators

• Sponsor: Walter and Eliza Hall Institute of Medical Research
• Collaborators: Johns Hopkins University
• Investigators: Principal Investigator: Sumitra Ananda, Associate Professor, Walter and Eliza Hall Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2017
• Primary Completion (Actual): December 31, 2020
• Study Completion (Anticipated): May 9, 2025

Study Registration Dates

• First Submitted: March 11, 2018
• First Submitted That Met QC Criteria: September 28, 2018
• First Posted (Actual): October 1, 2018

Study Record Updates

• Last Update Posted (Actual): May 9, 2023
• Last Update Submitted That Met QC Criteria: May 8, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: WEHI-ctDNA-10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All patients will be provided with a unique code number for the purposes of transferring information. Any data that leave the hospital will be coded. this information does not include patient's name or other personal identifiers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No