Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Cystadenocarcinoma, Serous

Cystadenocarcinoma

Fallopian Tube Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Fallopian Tube Diseases

Adenocarcinoma

Neoplasms, Cystic, Mucinous, and Serous

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Adenocarcinoma of the Appendix

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.

Patients with non-malignant gynecological conditions indicating surgical procedure, either salpingo-oophorectomy, hysterectomy or hysteroscopy.

Healthy women with genetically high risk for developing ovarian cancer, who have not undergone risk reducing procedure.

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.

Uterine lavage

5-10mL of blood will be drawn from participants.

Blood sample

Uterine lavage catheter

Keren Levanon, MD, PhD

Shunit Armon, MD

Yfat Kadan, MD

Ram Eitan, MD

Ariella Jakobson-Setton, MD

Tamar Perri, MD

Keren Levanon, MD,PhD

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.

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.

Biomarkers for Early Detection of Ovarian Cancer Using Uterine Lavage

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

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

Assessment of complications rate based on patient's questionnaire and medical records

Assessment of cost-effectiveness of uterine lavage-based diagnostic test for high risk population, including direct and indirect costs

Rabin Medical Center

Meir Medical Center

Shaare Zedek Medical Center

Sheba Medical Center

Spots Global Cancer Trial Database for uterine lavage catheter