Developing a Test for the Detection of Ovarian Cancer

April 29, 2022 updated by: Steven Skates, Massachusetts General Hospital

Ovarian Cancer Detection by Uterine Lavage DNA and Serum Proteins: a Phase 2 Biomarker Study

The study aims to develop a test for early detection of ovarian cancer using DNA from a growth involving the ovary found in a washing of the uterus (womb), and proteins found in the blood. The samples of the wash and the blood will be taken before surgery. After surgery, doctors will determine whether the participant had ovarian cancer or a benign disease of the ovaries. The tests of the washings and the blood will be examined to see how much the participants with ovarian cancer can be separated from the participants with a benign ovarian disease by the tests. Small amounts from the washing and the blood samples will be sent to four sites for analysis.

Statistical analyses of these data will compare tumor DNA found in the washing of the uterus with proteins in the blood to detect cases of ovarian cancer. The primary goal is to find tests that are mostly positive for cases of ovarian cancer and mostly negative for patients with benign disease. It is hoped that if the tests work for participants with symptoms of the disease that these tests will also work when testing women who have no symptoms. A new study would be needed to see if the tests worked in this situation. If the tests work, this could lead to increasing the number of cases detected in early stage disease and decreasing the number of cases detected in late stage disease. If this change in late stage is large, it will likely reduce deaths due to ovarian cancer.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The study aims to elucidate the relative contributions to detection of ovarian cancer from tumor DNA in uterine lavage (UL) and protein biomarkers from blood using newly available detection and sample collection technologies. In this document, the term "ovarian cancer" includes fallopian tube cancer. In the first cohort, the study will enroll 200 participants. Enrolling participants prior to surgical diagnosis (e.g. laparoscopy or paracentesis) ensures the study will be "Prospective Collection of Samples, Blinded Evaluation" (PRoBE) compliant. The expectation is that ~50 of these participants will have pathologically confirmed ovarian cancer. In a second cohort, 50 participants will be enrolled. Based on published reports, it is expected that ~5 participants will have microscopic or low volume ovarian cancer. In each cohort, the participants with a pathologic invasive epithelial ovarian cancer diagnosis will be defined as Cases and participants without any ovarian cancer, primary peritoneal cancer (PPC), or other cancer identified due to the surgery, will be defined as Controls. Other cancer groups are: (i) PPC, (ii) non-invasive serous tubal intraepithelial carcinoma (STIC) lesions, (iii) non-epithelial ovarian cancers, and (iv) non-ovarian cancers.

Two sites will sequence DNA obtained from uterine lavages to detect tumor-derived DNA (tDNA): one will carry out Duplex Sequencing of TP53 and the second site will carry out Haloplex sequencing of an 18-gene panel. Two other sites will assay serum proteins: the first will use clinical grade assays for CA125 and HE4, and the second will use research grade assays for these two proteins plus four additional protein biomarker candidates. Statistical analyses of these data will evaluate the relative utility of tDNA and plasma proteins to detect Cases (sensitivity) while limiting detection of Controls (specificity) in these two cohorts. Remaining DNA from UL and blood based biospecimens in form of plasma, serum, and buffy coat will be stored at a biorepository at NCI Frederick for future biomarker investigations which include (but are not limited to) other methods of detecting tDNA from UL, tDNA from plasma, exosomal markers, and additional blood-based and UL biomarker candidates.

Primary objectives:

  1. To collect samples from 200 participants with suspected ovarian cancer (of which ~50 or more are expected to have pathologically confirmed ovarian cancer) and 50 participants undergoing a risk-reducing salpingo-oophorectomy (of which ~5 are expected to have microscopic or low volume ovarian cancer).
  2. To test the tDNA from uterine lavage samples for tumor-derived TP53 mutations, using Duplex sequencing, and for potential abnormalities in an 18-gene panel, using Haloplex sequencing
  3. To test the serum proteins with two assays: the first will use clinical grade assays for CA125 and HE4, and the second will use research grade assays for these two proteins plus four additional protein biomarker candidates.

Outline: Participants undergo two blood draws (one required, one optional) up to 31 days before surgery and a uterine lavage at the time of planned surgery. The tDNA and serum proteins are then extracted from the samples and sent for analysis.

Study Type

Observational

Enrollment (Anticipated)

250

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Recruiting
        • University of Arkansas for Medical Sciences
        • Principal Investigator:
          • Kristin Zorn, MD
    • California
      • San Francisco, California, United States, 94115
        • Not yet recruiting
        • Kaiser Permanente - San Francisco
        • Contact:
        • Principal Investigator:
          • Christine Garcia, MD
    • Maryland
      • Annapolis, Maryland, United States, 21401
        • Recruiting
        • Anne Arundel Health System
        • Contact:
        • Principal Investigator:
          • Monica Jones, MD
      • Baltimore, Maryland, United States, 21218
        • Recruiting
        • Johns Hopkins University School of Medicine
        • Contact:
        • Principal Investigator:
          • Rebecca Stone, MD
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Not yet recruiting
        • Massachusetts General Hospital
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98122
        • Recruiting
        • The Swedish Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

Cohorts will be selected from patients scheduled for ovarian disorder-related surgeries across six sites: Massachusetts General Hospital in Boston, Massachusetts; Anne Arundel Health System in Annapolis, Maryland; Johns Hopkins University School of Medicine in Baltimore, Maryland; Kaiser Permanente - San Francisco in San Francisco, California; the Swedish Medical Center in Seattle, Washington; and the University of Arkansas for Medical Sciences in Little Rock, Arkansas.

Description

Inclusion Criteria:

  • Has intact uterus (no history of uterine ablation, tubal ligation or bilateral salpingectomy)
  • Cohort 1 (n=200 participants): Women scheduled for surgery or diagnostic laparoscopy for suspected but undiagnosed ovarian/fallopian tube cancer
  • Cohort 2 (n=50 participants): Known BRCA1 or BRCA2 mutation carrier scheduled for risk-reducing salpingo-oophorectomy

Exclusion Criteria:

  • Current tissue or cytology diagnostic procedure positive for ovary cancer or any cancer
  • Inability to provide informed consent
  • Age less than 30 years
  • Inability to obtain the minimum amount of blood
  • Inability to obtain the minimum amount of uterine lavage sample
  • At risk if blood were drawn (e.g. hemophilia, serious anemia- Hb less than 8.0 gm/dL)
  • Prior history of known ovarian or endometrial cancer
  • Treatment less than 1 year (excluding hormonal therapy) for cancer that spread beyond its origin
  • History of untreated high-grade cervical dysplasia (CIN3)
  • History of treated high grade cervical dysplasia (CIN3) with a cytologically abnormal pap smear within the past year. If there is no post treatment Pap smear in the medical record, perform a Pap smear prior to the day of surgery. If this Pap smear is abnormal, the participant is ineligible.
  • Currently pregnant
  • Known Lynch syndrome

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Pelvic Mass Cohort (cohort #1)
200 participants scheduled for surgery for suspected ovarian cancer due to a pelvic mass but without a confirmed tissue or cytology diagnosis.
Diagnostic test: Uterine lavage, or a wash of the womb
Uterine lavage is performed during surgery using a flexible, 3-way balloon tipped catheter. The catheter is inserted through the cervix, the balloon expanded and the uterine cavity lavaged using 10 cc of sterile saline which is collected, processed and stored for later analysis.
Diagnostic test: Blood sample
Participants undergo two blood draws (one required, one optional) up to 31 days before surgery
Diagnostic test: Pap smear
Participants undergo a standard Papanicolaou smear to collect cells and fluid from the cervix.
BRCA1/2 Carriers Cohort (cohort #2)
50 participants with an inherited BRCA1 or BRCA2 deleterious mutation without suspected ovarian cancers who are scheduled for risk-reducing salpingo-oophorectomy (RRSO) to remove ovaries and fallopian tubes.
Diagnostic test: Uterine lavage, or a wash of the womb
Uterine lavage is performed during surgery using a flexible, 3-way balloon tipped catheter. The catheter is inserted through the cervix, the balloon expanded and the uterine cavity lavaged using 10 cc of sterile saline which is collected, processed and stored for later analysis.
Diagnostic test: Blood sample
Participants undergo two blood draws (one required, one optional) up to 31 days before surgery
Diagnostic test: Pap smear
Participants undergo a standard Papanicolaou smear to collect cells and fluid from the cervix.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Genomic biomarkers assessing mutations and methylation of tumor DNA, and protein biomarkers measured as the concentration of a protein in pg/mL, both types of biomarkers measured in the collected biospecimens.
Time Frame: Through study completion, an average of three years
Biomarkers that distinguish between ovarian cancer and benign ovarian disease
Through study completion, an average of three years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Collaborators

Johns Hopkins University
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
McGill University
Fred Hutchinson Cancer Center
Kaiser Permanente
University of Arkansas
Swedish Medical Center
Anne Arundel Health System Research Institute
TwinStrand Biosciences

Investigators

  • Study Director: Christos Patriotis, PhD, National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 13, 2020

Primary Completion (ANTICIPATED)

March 1, 2023

Study Completion (ANTICIPATED)

March 1, 2025

Study Registration Dates

First Submitted

February 19, 2021

First Submitted That Met QC Criteria

March 9, 2021

First Posted (ACTUAL)

March 12, 2021

Study Record Updates

Last Update Posted (ACTUAL)

May 3, 2022

Last Update Submitted That Met QC Criteria

April 29, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20-450
  • 5U01CA152990 (NIH)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data is not anticipated to be shared.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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