Biomarkers for Early Detection of Ovarian Cancer Using Uterine Lavage

Ovarian Cancer Clinical Trial

— BEDOCA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03150121
• Other study ID #: SHEBA-13-0930-KL-CTIL
• Status: Recruiting
• Phase: N/A
• Start date: June 29, 2014
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2020
• Source: Sheba Medical Center
• Contact: Keren Levanon, MD, PhD
• Phone: +972-3-5304961
• Email: Keren.Levanon[@]sheba.health.gov.il
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Ovarian Epithelial
• Cystadenocarcinoma
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Ovarian Carcinoma
• Ovarian Neoplasms
• Primary Peritoneal Carcinoma
• Serous Cystadenocarcinoma

Intervention

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.
• 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.

Locations

Country	Name	City	State
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Meir Medical Center	Kfar Saba
Israel	Rabin Medical Center	Peta? Tiqwa
Israel	Sheba Medical Center	Ramat Gan

Sponsors (4)

Lead Sponsor	Collaborator
Sheba Medical Center	Meir Medical Center, Rabin Medical Center, Shaare Zedek Medical Center

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ability of uterine lavage-based biomarkers to detect early stage ovarian cancer	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	Complications rate of uterine lavage procedure in high risk population	Assessment of complications rate based on patient's questionnaire and medical records	7 years
Secondary	Burden of uterine lavage procedure as routine diagnostic test for high risk population	Assessment of cost-effectiveness of uterine lavage-based diagnostic test for high risk population, including direct and indirect costs	7 years