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 Information
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
Administrative Informations
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