Leveraging Methylated DNA Markers (MDMs) in the Detection of Endometrial Cancer, Ovarian Cancer, and Cervical Cancer

Recruiting

• Conditions: Ovarian Cancer; Atypical Endometrial Hyperplasia; Adnexal Mass; Cervical Cancer; Endometrial Cancer; Cervical Dysplasia

• Registration Number: NCT05051722
• Lead Sponsor: Mayo Clinic

Brief Summary

The overarching objective of this project is to develop a pan-gynecologic cancer detection test using gynecologic (unique endometrial, cervical, and ovarian cancer) cancer-specific methylated DNA markers and high-risk human papilloma virus (HR-HPV) detected in vaginal fluid and/or plasma.

This proposal defines Phase II MDM-based cancer detection studies in endometrial cancer (EC) and endometrial hyperplasia with atypia (AEH) in vaginal fluid and 2) ovarian cancer (OC) in plasma and vaginal fluid. Additionally, it defines necessary Phase I MDM-based cancer detection and exploratory aims to test novel cervical cancer (CC) MDMs and test the specificity of cancer-specific MDMs among various common benign gynecologic pathologies.er detection and exploratory aims to test novel cervical cancer MDMs and test the specificity of cancer-specific MDMs among various common benign gynecologic pathologies.

Detailed Description

Detection of endometrial, ovarian, and cervical cancers at an early stage vastly increases the chances of cure and may also avert morbidity secondary to surgical staging, radiation, and/or chemotherapy. Despite the great successes of cervical cancer screening, comparable early detection methods for other gynecologic cancers and their precursors are not available. While nearly 1.5 million women per year in the United States are evaluated for abnormal uterine bleeding (AUB) or postmenopausal bleeding (PMB), the most common symptom of endometrial cancer, most undergo an invasive diagnostic biopsy with the finding of benign etiology.

Vaginal bleeding is often the only presenting symptom of women ultimately diagnosed with endometrial cancer (EC) or its precursor lesion, endometrial hyperplasia(EH). More than 90% of women with EC present with vaginal bleeding. Cervical cancer and cervical dysplasia can present as intermenstrual bleeding, post-coital bleeding, or other abnormal vaginal bleeding. However, most women who present with AUB or PMB have a benign etiology.

There are approximately 70 million women ≥45 years of age in the United States based on the most recent census data. Between 4-11% of women will be worked up for perimenopausal AUB or PMB in their lifetime. As only 5-10% of those women will have an EC or EH, there is a great clinical need for a less invasive clinical diagnostic test that can reliably distinguish between benign uterine bleeding and bleeding associated with an underlying endometrial cancer, cervical cancer, or a precursor lesion.

Study Timeline

• Study Start: 2021-08-03
• Study First Submitted: 2021-09-11
• Study First Submitted QC: 2021-09-11
• Study First Posted: 2021-09-21
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-09
• Last Update Posted: 2025-06-11
• Primary Completion: 2026-10-31
• Study Completion: 2026-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 3110

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Develop predictive models from a panel of EC-specific MDMs and validate their performance in identifying underlying EC and AEH within vaginal fluid in a larger, more diverse cohort.	18 months	Complete a phase II biomarker development study of a methylated DNA marker (MDM)-based endometrial cancer detection test performed on vaginal fluid. The phase II aspect of this biomarker development study will narrow the number of endometrial cancer MDMs within the biomarker panel in order to optimize the next phase of test development.
Develop predictive models from a panel of OC-specific MDMs and validate their performance in identifying underlying OC within vaginal fluid and plasma in a larger, more diverse cohort.	18 months	Complete a phase II biomarker development study of a methylated DNA marker (MDM)-based ovarian cancer detection test performed on vaginal fluid. The phase II aspect of this biomarker development study will narrow the number of ovarian cancer MDMs within the biomarker panel in order to optimize the next phase of test development.

Secondary Outcome Measures

Name	Time	Method
Using 95% specificity cutoffs of the final MDM EC panel, determine the false positive rate among women undergoing surgical removal of common benign gynecologic pathology	18 months	As part of this biomarker test development, understanding whether common non-cancerous uterine or gynecologic conditions may also lead to the finding of currently apparent endometrial cancer-specific MDMs in vaginal fluid is critical in determining specificity, positive predictive value, and negative predictive value of the test.

Trial Locations

Locations (17)

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

My GYN Care; 🇺🇸 Miami, Florida, United States

Genoma Research, Inc.; 🇺🇸 Miami, Florida, United States

Signature Women's Healthcare, LLC; 🇺🇸 Pembroke Pines, Florida, United States

Sarasota Memorial Health Care System; 🇺🇸 Sarasota, Florida, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States

Providea Health Partners, LLC; 🇺🇸 Evergreen Park, Illinois, United States

Ochsner Clinic Foundation; 🇺🇸 New Orleans, Louisiana, United States

Valley OB-GYN Clinic; 🇺🇸 Saginaw, Michigan, United States

University of Mississippi Medical Center; 🇺🇸 Jackson, Mississippi, United States

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