Biomarkers for Early Detection of Ovarian Cancer Using Uterine Lavage

Brief Title

Biomarkers for Early Detection of Ovarian Cancer Using Uterine Lavage

Official Title

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

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.
    

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

Primary Outcome

Ability of uterine lavage-based biomarkers to detect early stage ovarian cancer

Secondary Outcome

 Complications rate of uterine lavage procedure in high risk population

Condition

Ovarian Cancer

Intervention

Uterine lavage

Study Arms / Comparison Groups

 Ovarian cancer patients

Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Procedure

Estimated Enrollment

500

Start Date

June 29, 2014

Completion Date

December 31, 2024

Primary Completion Date

December 31, 2022

Eligibility Criteria

        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.
      

Gender

Female

Ages

18 Years - 80 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Keren Levanon, MD,PhD, +972-3-5304961, [email protected]

Location Countries

Israel

Location Countries

Israel

NCT ID

NCT03150121

Organization ID

SHEBA-13-0930-KL-CTIL

Responsible Party

Sponsor

Study Sponsor

Sheba Medical Center

Collaborators

 Rabin Medical Center

Study Sponsor

Keren Levanon, MD,PhD, Principal Investigator, Sheba Medical Center

Verification Date

February 2020