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

NCT ID: NCT05051722

Last Updated: 2026-01-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

3110 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-08-03

Study Completion Date

2027-06-30

Brief Summary

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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

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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.

Conditions

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Endometrial Cancer Cervical Cancer Atypical Endometrial Hyperplasia Cervical Dysplasia Adnexal Mass Ovarian Cancer

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Cohort 1 - AUB / PMB

Patients ≥45 years of age, presenting with abnormal uterine bleeding (AUB) or post-menopausal bleeding (PMB). Patients ages 18 - 44 years of age, presenting with abnormal uterine bleeding (AUB) and a risk factor for endometrial cancer (BMI ≥30 or PCOS or Tamoxifen use). These presenting symptoms clinically warrant evaluation such as an endometrial biopsy to assess for underlying endometrial cancer, endometrial hyperplasia or other endometrial pathology.

Vaginal Fluid Collection

Intervention Type DIAGNOSTIC_TEST

A sample of vaginal fluid will be collected from each participant, prior to any exams or procedures, by a healthcare provider using a small vaginal swab.

Blood Collection

Intervention Type DIAGNOSTIC_TEST

A blood sample will be collected from each participant prior to undergoing any exams or procedures.

Cohort 2 - Biopsy-proven EC or AEH or EIN

Patients ≥18 years of age with biopsy-proven endometrial cancer (EC), atypical endometrial hyperplasia (AEH), or endometrial intraepithelial neoplasia (EIN) presenting for surgical management of their endometrial pathology.

Vaginal Fluid Collection

Intervention Type DIAGNOSTIC_TEST

A sample of vaginal fluid will be collected from each participant, prior to any exams or procedures, by a healthcare provider using a small vaginal swab.

Blood Collection

Intervention Type DIAGNOSTIC_TEST

A blood sample will be collected from each participant prior to undergoing any exams or procedures.

Cohort 3 - Cervix pathology

Patients ≥18 years of age presenting for a clinically indicated colposcopy, cervical biopsy, or surgical excision, as follow-up for an abnormal Pap test or cervical mass identified on physical exam. Final clinical diagnoses within this cohort may include mild cervical intraepithelial neoplasia (CIN 1), moderate and/or severe CIN (CIN 2/3), adenocarcinoma in situ (AIS), invasive cervical cancers (adenocarcinoma or squamous cell carcinoma), or possibly benign findings.

Vaginal Fluid Collection

Intervention Type DIAGNOSTIC_TEST

A sample of vaginal fluid will be collected from each participant, prior to any exams or procedures, by a healthcare provider using a small vaginal swab.

Blood Collection

Intervention Type DIAGNOSTIC_TEST

A blood sample will be collected from each participant prior to undergoing any exams or procedures.

Cohort 4 - Benign Uterine Pathology

Patients with any of four benign gynecologic conditions including: uterine fibroids, benign endometrial polyps, adenomyosis and endometriosis. All patients enrolled in this cohort will be undergoing clinically indicated gynecologic surgery (hysterectomy, myomectomy, polypectomy, or laparoscopic tissue excision) for the specific benign gynecologic condition. Verification of the final benign diagnosis will be based on pathology diagnosis of clinically-indicated tissue removed during surgery.

Vaginal Fluid Collection

Intervention Type DIAGNOSTIC_TEST

A sample of vaginal fluid will be collected from each participant, prior to any exams or procedures, by a healthcare provider using a small vaginal swab.

Blood Collection

Intervention Type DIAGNOSTIC_TEST

A blood sample will be collected from each participant prior to undergoing any exams or procedures.

Cohort 5 - Healthy Control Women

Healthy patients with a uterus, ≥45 years of age presenting for GYN wellness exam to serve as a control group. These patients will have no clinically evident gynecologic precancers, gynecologic cancers, or clinically evident or symptomatic benign gynecologic conditions. These patients will not have known or clinically suspected AUB, PMB, fibroids, endometriosis, benign endometrial polyps, or adenomyosis, nor will they have any active gynecologic or non-gynecologic acute medical conditions.

Vaginal Fluid Collection

Intervention Type DIAGNOSTIC_TEST

A sample of vaginal fluid will be collected from each participant, prior to any exams or procedures, by a healthcare provider using a small vaginal swab.

Blood Collection

Intervention Type DIAGNOSTIC_TEST

A blood sample will be collected from each participant prior to undergoing any exams or procedures.

Cohort 6- Isolated Adnexal Mass Cohort (ovarian or fallopian mass)

Patients ≥50 years of age and postmenopausal (12 months since LMP or available blood hormone levels confirming postmenopausal status) and an isolated adnexal mass or isolated bilateral adnexal masses being surgically removed. These patients may have a final diagnosis of any of the following: benign ovarian neoplasm, borderline tumor of the ovary, or clinically early-stage OC.

Vaginal Fluid Collection

Intervention Type DIAGNOSTIC_TEST

A sample of vaginal fluid will be collected from each participant, prior to any exams or procedures, by a healthcare provider using a small vaginal swab.

Blood Collection

Intervention Type DIAGNOSTIC_TEST

A blood sample will be collected from each participant prior to undergoing any exams or procedures.

Cohort 7 - OC Cohort - Biopsy proven or clinically suspected ovarian cancer (OC)

Patients ≥18 years of age with ovarian cancer (OC) (clinically probable based on distribution of pelvic/abdominal masses on imaging, elevated CA-125, ascites, and/or imaging-guided biopsy proven) presenting for neoadjuvant chemotherapy or primary surgical management (debulking or staging) of their OC. The umbrella of OC also includes fallopian tube cancer and primary peritoneal cancer. All histologies are eligible for enrollment.

Vaginal Fluid Collection

Intervention Type DIAGNOSTIC_TEST

A sample of vaginal fluid will be collected from each participant, prior to any exams or procedures, by a healthcare provider using a small vaginal swab.

Blood Collection

Intervention Type DIAGNOSTIC_TEST

A blood sample will be collected from each participant prior to undergoing any exams or procedures.

Interventions

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Vaginal Fluid Collection

A sample of vaginal fluid will be collected from each participant, prior to any exams or procedures, by a healthcare provider using a small vaginal swab.

Intervention Type DIAGNOSTIC_TEST

Blood Collection

A blood sample will be collected from each participant prior to undergoing any exams or procedures.

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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Vaginal Fluid

Eligibility Criteria

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Inclusion Criteria

Patients will be ≥45 years of age and meet one of the following criteria:

* Abnormal uterine bleeding
* Postmenopausal bleeding

OR

Patients ages 18 - 44 years of age and meet these criteria

* Abnormal uterine bleeding
* One risk factor for endometrial cancer (BMI ≥30 or PCOS or Tamoxifen use)


Patients will be ≥18 years of age and meet at least one of the following criteria:

* Presence of biopsy-proven EC (any histology, including uterine carcinosarcoma) and surgical intervention planned. Surgical intervention can include any of the following: hysterectomy, D\&C, hysteroscopic resection
* Biopsy showing AEH or EIN with surgical intervention planned. Surgical intervention can include any of the following: hysterectomy, D\&C, hysteroscopic resection, etc)


Patients will be ≥18 years of age, have a cervix and meet at least one of the following criteria:

* History of current abnormal cervical/endocervical Pap test for which the patient is presenting for colposcopy
* Cervical mass identified on physical exam and patient referred for cervical biopsy, even if colposcopy not recommended or indicated
* Planned clinically indicated surgical excisional biopsy or removal of the cervix (cold knife cone, LEEP, hysterectomy) for abnormal Pap test, cervical dysplasia, cervical mass, or biopsy-proven invasive cervical cancer (adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, or less common primary cervical carcinomas all eligible)


Patients will be ≥45 years of age and should meet at least one of the following criteria:

* Undergoing hysterectomy with biopsy-proven or clinically presumed (based on imaging and/or clinical symptoms) benign gynecologic or uterine pathology of fibroids, endometriosis, adenomyosis, or benign endometrial polyps.
* Undergoing any gynecologic surgery in which a benign pathologic tissue diagnosis of fibroids, endometriosis, adenomyosis, or benign endometrial polyp is anticipated to be confirmed.


Patients with a uterus will be ≥45 years of age and should meet the following criteria:

* Presenting for GYN wellness exam, ± Pap test
* No change in medical conditions, new diagnoses, or new medications within the past 6 months


Patients ≥50 years of age and:

* Postmenopausal
* At least 1 intact ovary
* Diagnosis of an adnexal mass or a clinical suspicion of early-stage ovarian cancer (including fallopian tube cancer)
* Planned surgery for the adnexal mass
* For vaginal fluid collection, patient must have a uterus, cervix and at least 1 intact fallopian tube\* (without prior tubal ligation/occlusion)


Women will be ≥18 years of age and meet the following criteria:

* Presence of clinically probable ovarian, fallopian tube, or primary peritoneal cancer (all under the umbrella of OC) based on clinical findings of any/all of the following: imaging showing adnexal and/or abdominal masses consistent with probable ovarian cancer, omental caking, elevated CA125, ascites, imaging-guided biopsy consistent with OC pathology
* Newly diagnosed with ovarian, fallopian tube or primary peritoneal cancer without neoadjuvant therapy
* At least one intact ovary
* For vaginal fluid collection, patient must have a uterus, cervix and at least 1 intact fallopian tube\* (without prior tubal ligation/occlusion)

Exclusion Criteria

* Prior hysterectomy
* Current known pregnancy diagnosis
* Any prior pelvic or vaginal radiotherapy
* Any prior cancer (except basal cell skin cancer) within the past 5 years
* Chemotherapy within the past 5 years
* Current biopsy-proven cervical, vaginal, or vulvar cancer or lower genital tract dysplasia
* Current biopsy-proven endometrial cancer or endometrial hyperplasia
* Current biopsy-proven benign endometrial polyp
* Endometrial biopsy/sampling within the preceding 1 month showing benign endometrium


* Undergoing surgical procedure for recurrent or metastatic EC
* Received preoperative neoadjuvant chemotherapy or radiotherapy for current EC diagnosis
* Prior hysterectomy
* Current known pregnancy diagnosis
* Prior or current biopsy-proven cervical cancer
* Presence of concomitant biopsy-proven cervical dysplasia
* Any prior pelvic or vaginal radiotherapy
* Any prior cancer (except basal cell skin cancer) within the past 5 years
* Chemotherapy within the past 5 years
* Prior intervention or surgery with intent to completely remove the target pathology


* History of pelvic or vaginal radiotherapy
* Prior total hysterectomy (cervix removed) for any indication
* Current known pregnancy diagnosis
* Cervical mass biopsy-proven to be EC or a cancer metastatic from a non-cervical origin
* Any prior cancer (except basal cell skin cancer) within the past 5 years
* Chemotherapy within the past 5 years
* Patients presenting for colposcopy as part of lower genital tract dysplasia or cancer surveillance after prior curative intent treatment and no current Pap abnormality or cervical mass
* Prior intervention or surgery with intent to completely remove the target pathology for the current lesion / diagnosis during the current episode


* Endometrial biopsy or office hysteroscopy within 2 weeks preceding the planned gynecologic surgery procedure for fibroids, endometriosis, benign endometrial polyps, or adenomyosis
* Any surgery within the past 3 months
* Prior hysterectomy
* Current known pregnancy diagnosis
* Prior or current biopsy-proven gynecologic cancer
* Current biopsy-proven AEH/EIN, cervical, vaginal, or vulvar dysplasia
* Prior pelvic or vaginal radiotherapy
* Any prior cancer (except basal cell skin cancer) within the past 5 years
* Chemotherapy within the past 5 years
* Undergoing hysterectomy for prolapse without a coexisting known or presumed benign uterine pathologic diagnosis of fibroids, endometriosis, benign endometrial polyps, or adenomyosis
* Prior intervention or surgery with intent to completely remove the target pathology for the current lesion / diagnosis during the current episode


* Pap test or cervical biopsy within the past 1 month
* Endometrial biopsy or office hysteroscopy within the past 1 month
* Any surgery within the past 3 months
* Prior hysterectomy
* Current known pregnancy diagnosis
* Prior or current biopsy-proven gynecologic cancer
* Current biopsy-proven AEH/EIN, cervical, vaginal, or vulvar dysplasia
* Prior pelvic or vaginal radiotherapy
* Any prior cancer (except basal cell skin cancer) within the past 5 years
* Chemotherapy within the past 5 years
* Criteria met for inclusion in any of the other study cohorts


* Any current or prior cancer diagnosis (except basal cell or squamous cell skin cancer, non-gyn)
* Chemotherapy for cancer treatment within the past 5 years prior to collection
* Clinically suspected advanced stage ovarian cancer (Stage III or IV) on presentation, if known prior to specimen collection
* Surgical candidates for recurrent ovarian cancer
* History of pelvic or vaginal radiation therapy
* Known current synchronous endometrial cancer or hyperplasia
* Known current cervical, vaginal, or vulvar dysplasia


* Patients with recurrent OC
* Any current or prior cancer diagnosis (except basal cell or squamous cell skin cancer, non-gyn) within the past 5 years
* Chemotherapy for cancer treatment within the past 5 years prior to collection
* History of pelvic or vaginal radiation therapy
* Known current synchronous endometrial cancer or hyperplasia
* Known current cervical, vaginal, or vulvar dysplasia
* Current known pregnancy diagnosis
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Mayo Clinic

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jamie N Bakkum-Gamez, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

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Mayo Clinic

Phoenix, Arizona, United States

Site Status RECRUITING

Mayo Clinic

Jacksonville, Florida, United States

Site Status RECRUITING

My GYN Care

Miami, Florida, United States

Site Status ACTIVE_NOT_RECRUITING

Genoma Research, Inc.

Miami, Florida, United States

Site Status RECRUITING

Orlando Health

Orlando, Florida, United States

Site Status RECRUITING

Signature Women's Healthcare, LLC

Pembroke Pines, Florida, United States

Site Status ACTIVE_NOT_RECRUITING

Sarasota Memorial Health Care System

Sarasota, Florida, United States

Site Status RECRUITING

Piedmont Healthcare

Atlanta, Georgia, United States

Site Status RECRUITING

University of Chicago

Chicago, Illinois, United States

Site Status RECRUITING

Providea Health Partners, LLC

Evergreen Park, Illinois, United States

Site Status ACTIVE_NOT_RECRUITING

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status RECRUITING

Valley OB-GYN Clinic

Saginaw, Michigan, United States

Site Status RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status RECRUITING

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status NOT_YET_RECRUITING

The Woman's Health Pavilion

Howard Beach, New York, United States

Site Status RECRUITING

The Woman's Health Pavilion

Westbury, New York, United States

Site Status RECRUITING

Altru Health System

Grand Forks, North Dakota, United States

Site Status RECRUITING

Cleveland Clinic

Cleveland, Ohio, United States

Site Status RECRUITING

Total Women's Care of the Heights

Houston, Texas, United States

Site Status RECRUITING

Medical Colleagues of Texas, LLP

Katy, Texas, United States

Site Status RECRUITING

Virginia Commonwealth University/ Massey Cancer Center

Richmond, Virginia, United States

Site Status RECRUITING

Mayo Clinic Health System - Northwest Wisconsin

Eau Claire, Wisconsin, United States

Site Status RECRUITING

Mayo Clinic Health System - Southwest Wisconsin

La Crosse, Wisconsin, United States

Site Status RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Maureen A Lemens, BSN

Role: CONTACT

507-293-1487

Clinical Trials Referral Office

Role: CONTACT

855-776-0015

Facility Contacts

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Debbie L Ryan, CCRP

Role: primary

480-342-1208

M

Role: backup

Ashley N Shelton, CRC

Role: primary

504-953-1594

Laura Lucia, BHSc, CRC

Role: primary

305-392-1264

Donya Shahnavaz, CRC

Role: primary

321-841-7303

Bianca Henry, CRC

Role: backup

Rachael Sanacore

Role: primary

Megan Swiger

Role: backup

Dionne Jean, CRC

Role: primary

404-425-7927

Calla O'Connor, MPH

Role: primary

Veronika Sesari

Role: backup

Ashley Samuel, CRC

Role: primary

504-703-2658

Veronica Hixon Calliet, BSN

Role: backup

504-703-8602

Jacqueline Lang, CCRC

Role: primary

989-272-9065

Maureen A Lemens, BSN

Role: primary

507-293-1487

Tanya Robinson, RN

Role: primary

601-815-2123

Kenna H Nettles, PA-C

Role: backup

601-815-5963

Monica Martinez, CRC

Role: primary

718-843-6300

Monica Martinez, CRC

Role: primary

718-843-6300

Alexis Tatum, CRC

Role: primary

701-780-1563

Tina Schmitz, BSN

Role: backup

701-780-1845

Tori Carpenter, CRC

Role: primary

Sarah Neale, CRC

Role: backup

Carmen Paz

Role: primary

346-330-5302

Erika Keller, CRC

Role: primary

281-769-8674

Gabriella Coletta, CRC

Role: backup

512-351-4565

Morgan DeHart

Role: primary

804-827-1266

Faith McFadden, MSN

Role: backup

804-628-0616

Stephanie L Larson, ACRC

Role: primary

715-838-1976

Christina M Scinto, ACRC

Role: backup

715-464-8172

Kate L Zboralski, ACRC

Role: primary

608-392-9521

Taylor Cammer, ACRC

Role: backup

608-392-9280

Jayashree Narayanon, CRC

Role: primary

414-805-6620

Maia Terashvili, Ph.D.

Role: backup

Related Links

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Other Identifiers

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NCI-2022-10826

Identifier Type: REGISTRY

Identifier Source: secondary_id

20-012833

Identifier Type: -

Identifier Source: org_study_id

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