Biomarkers for Early Detection of Ovarian Cancer Using Uterine Lavage (BEDOCA)

February 24, 2020 updated by: Sheba Medical Center

Identification of Novel Biomarkers for Early Detection of Ovarian Cancer in High-risk and Normal-risk Populations Using Uterine Lavage

Screening programs for high-grade ovarian carcinoma failed to reduce disease-specific mortality, since they do not offer early enough detection of the disease. Most cases of high grade ovarian cancer develop in the fallopian tubes, hence the universal recommendation for high-risk populations (e.g., BRCA1/2 mutation carriers) is to undergo risk-reducing bilateral salpingo-oophorectomy (RRBSO) around the age of 40. The aims of this trial are: (1) to identify novel early-stage disease biomarkers using liquid biopsies obtained through uterine lavage, and (2) to optimize the technique a of uterine lavage and the processing of the samples for ultimate implementation as a routine diagnostic test for high risk populations.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Brief Summary:

Screening programs for high-grade ovarian carcinoma failed to reduce disease-specific mortality, since they do not offer early enough detection of the disease. Most cases of high grade ovarian cancer develop in the fallopian tubes, hence the universal recommendation for high-risk populations (e.g., BRCA1/2 mutation carriers) is to undergo risk-reducing bilateral salpingo-oophorectomy (RRBSO) around the age of 40. The aims of this trial are: (1) to identify novel early-stage disease biomarkers using liquid biopsies obtained through uterine lavage, and (2) to optimize the technique a of uterine lavage and the processing of the samples for ultimate implementation as a routine diagnostic test for high risk populations.

The end point of the study is sensitivity and specificity of a liquid biopsy test based on uterine lavage for detection of ovarian cancer.

The study enrolls two cohorts:

  1. Proof-of-principle cohort - patients with either established ovarian cancer or other, non-malignant, gynecological conditions.
  2. High risk cohort - healthy women at genetically high-risk for ovarian cancer who have not undergone RRBSO.

Inclusion criteria include age over 18, ability to read, understand and sign informed consent form, and planned surgical procedure with general anesthesia (for the proof-of-principle cohort), or planned regular gynecological examination due to high-risk for developing ovarian cancer (high risk cohort).

Exclusion criteria include pregnancy or current attempts to conceive, any prior condition that precludes washing of the entire fallopian tubes.

Patients will provide signed informed consent and will undergo uterine lavage which will be performed by a surgeon before surgery, after induction of anesthesia (proof-of-principle cohort), or by a gynecologist during gynecological examination in an office setting (high risk cohort). Uterine lavage is performed using an intrauterine insemination catheter or rigid pipelle uterine sampler. The catheter is inserted into the cervical canal. 10mL of saline are infused into the uterine cavity and fallopian tubes and immediately retrieved. 5-10mL of blood is also collected from each participant. Patients who have undergone the procedure without anesthesia are requested to complete a pain and stress score questionnaire. All patients are asked to allow access of their medical records and pathology reports from past, present and future gynecologic surgeries.

The uterine lavage liquid biopsy samples are centrifuged to eliminate cells and cell debris. Supernatants were aliquoted within 6 hours from the procedure. Microvesicles, total RNA and DNA are isolated according to previously published protocols.

The samples of the proof-of-principle cohort will be used to define an optimized set of assays, measuring either protein-based or nucleic acid-based biomarkers.

The samples of the high risk cohort will be used to test the sensitivity and specificity of the previously defined biomarkers, and to evaluate confounding factors that may affect the accuracy of the test, such as menopausal status and breast cancer endocrine therapy. Each participant will be asked to consent to uterine lavage procedure on subsequent follow-up visits.

Study Type

Interventional

Enrollment (Anticipated)

500

Phase

  • Not Applicable

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

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

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Subject must be at least 18 years of age.
  • Subject must have all gynecological organs, including: vagina, cervix, uterus, fallopian tubes and ovaries.

  • For the proof-of-principle cohort:

    • Subject must have been evaluated for a gynecologic condition, for which the treating physician has determined that a surgical intervention is required. The surgical procedure may be either: hysterectomy, surgical hysteroscopy, or salpingo-oophorectomy.
    • The eligible gynecological diagnoses include: high grade ovarian, fallopian tube or primary peritoneal carcinoma, or any non-malignant gynecologic condition.

  • For the high risk cohort:

    • Subject must have an increased risk for developing ovarian cancer, as determined by genetic testing for BRCA1 or BRCA2 mutations, or by family history of at least one first degree relative that has been diagnosed with high grade ovarian cancer.

Exclusion Criteria:

  • Subject is pregnant or is currently attempting to conceive.
  • Subject has undergone resection of the uterus, fallopian tubes or ovaries.
  • Subject is unable to read, understand and sign the informed consent form.
  • Subject refuses to allow access to medical records or pathology reports.

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

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ovarian cancer patients
High grade ovarian/fallopian tube/primary peritoneal carcinoma patients with current active disease, at any stage and histological type, who have not yet undergone debulking surgery.
Procedure: Uterine lavage
Uterine lavage is performed using an intrauterine insemination catheter or rigid pipelle uterine sampler. The catheter is inserted into the cervical canal. 10mL of saline are infused into the uterine cavity and fallopian tubes and immediately retrieved.
Other Names:
  • Tubo-uterine lavage
Procedure: Blood sample
5-10mL of blood will be drawn from participants.
Device: Uterine lavage catheter
Uterine lavage is performed using an intrauterine insemination catheter or rigid pipelle uterine sampler. The catheter is inserted into the cervical canal. 10mL of saline are infused into the uterine cavity and fallopian tubes and immediately retrieved.
Other Names:
  • Intrauterine insemination catheter
Active Comparator: Non-malignant controls
Patients with non-malignant gynecological conditions indicating surgical procedure, either salpingo-oophorectomy, hysterectomy or hysteroscopy.
Procedure: Uterine lavage
Uterine lavage is performed using an intrauterine insemination catheter or rigid pipelle uterine sampler. The catheter is inserted into the cervical canal. 10mL of saline are infused into the uterine cavity and fallopian tubes and immediately retrieved.
Other Names:
  • Tubo-uterine lavage
Procedure: Blood sample
5-10mL of blood will be drawn from participants.
Device: Uterine lavage catheter
Uterine lavage is performed using an intrauterine insemination catheter or rigid pipelle uterine sampler. The catheter is inserted into the cervical canal. 10mL of saline are infused into the uterine cavity and fallopian tubes and immediately retrieved.
Other Names:
  • Intrauterine insemination catheter
Experimental: High risk population
Healthy women with genetically high risk for developing ovarian cancer, who have not undergone risk reducing procedure.
Procedure: Uterine lavage
Uterine lavage is performed using an intrauterine insemination catheter or rigid pipelle uterine sampler. The catheter is inserted into the cervical canal. 10mL of saline are infused into the uterine cavity and fallopian tubes and immediately retrieved.
Other Names:
  • Tubo-uterine lavage
Procedure: Blood sample
5-10mL of blood will be drawn from participants.
Device: Uterine lavage catheter
Uterine lavage is performed using an intrauterine insemination catheter or rigid pipelle uterine sampler. The catheter is inserted into the cervical canal. 10mL of saline are infused into the uterine cavity and fallopian tubes and immediately retrieved.
Other Names:
  • Intrauterine insemination catheter

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ability of uterine lavage-based biomarkers to detect early stage ovarian cancer
Time Frame: 7 years
Sensitivity and specificity of proteomic and genomic biomarkers measured in uterine lavage liquid biopsies. The samples will be analyzed in a blinded fashion. The pathological data of the patients will be reviewed and the sensitivity/specificity of each biomarker will be calculated
7 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complications rate of uterine lavage procedure in high risk population
Time Frame: 7 years
Assessment of complications rate based on patient's questionnaire and medical records
7 years
Burden of uterine lavage procedure as routine diagnostic test for high risk population
Time Frame: 7 years
Assessment of cost-effectiveness of uterine lavage-based diagnostic test for high risk population, including direct and indirect costs
7 years

Collaborators and Investigators

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

Sponsor

Sheba Medical Center

Collaborators

Rabin Medical Center
Meir Medical Center
Shaare Zedek Medical Center

Investigators

  • Principal Investigator: Keren Levanon, MD,PhD, Sheba Medical Center
  • Principal Investigator: Yfat Kadan, MD, Meir Medical Center
  • Principal Investigator: Ram Eitan, MD, Rabin Medical Center

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)

June 29, 2014

Primary Completion (Anticipated)

December 31, 2022

Study Completion (Anticipated)

December 31, 2024

Study Registration Dates

First Submitted

May 3, 2017

First Submitted That Met QC Criteria

May 9, 2017

First Posted (Actual)

May 12, 2017

Study Record Updates

Last Update Posted (Actual)

February 26, 2020

Last Update Submitted That Met QC Criteria

February 24, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SHEBA-13-0930-KL-CTIL

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

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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