Leveraging Methylated DNA Markers (MDMs) in the Detection of Endometrial Cancer, Ovarian Cancer, and Cervical Cancer
- Conditions
- Ovarian CancerAtypical Endometrial HyperplasiaAdnexal MassCervical CancerEndometrial CancerCervical Dysplasia
- Interventions
- Diagnostic Test: Tampon CollectionDiagnostic Test: Blood Collection
- 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 tampon-collected vaginal fluid and 2) ovarian cancer (OC) in plasma and tampon-collected 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 2640
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Cohort 1 - AUB / PMB Blood Collection Women ≥45 years of age, presenting with abnormal uterine bleeding (AUB) or post-menopausal bleeding (PMB). These presenting symptoms clinically warrant evaluation such as an endometrial biopsy to assess for underlying endometrial cancer, endometrial hyperplasia or other endometrial pathology. Cohort 3 - Cervix pathology Blood Collection Women ≥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. Cohort 2 - Biopsy-proven EC or AEH or EIN Blood Collection Women ≥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. Cohort 5 - Healthy Control Women Blood Collection Healthy women ≥45 years of age presenting for well-woman exams to serve as a control group. These women will have no clinically evident gynecologic precancers, gynecologic cancers, or clinically evident or symptomatic benign gynecologic conditions. These women 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. Cohort 2 - Biopsy-proven EC or AEH or EIN Tampon Collection Women ≥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. Cohort 4 - Benign Uterine Pathology Blood Collection Women with any of four benign gynecologic conditions including: uterine fibroids, benign endometrial polyps, adenomyosis and endometriosis. All women 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. Cohort 6- Isolated Adnexal Mass Cohort (ovarian or fallopian mass) Tampon Collection Women ≥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 will have a final diagnosis of any of the following: benign ovarian neoplasm, borderline tumor of the ovary, or clinically early-stage OC. Cohort 6- Isolated Adnexal Mass Cohort (ovarian or fallopian mass) Blood Collection Women ≥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 will have a final diagnosis of any of the following: benign ovarian neoplasm, borderline tumor of the ovary, or clinically early-stage OC. Cohort 7 - OC Cohort - Biopsy proven or clinically suspected ovarian cancer (OC) Blood Collection Women ≥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. Cohort 1 - AUB / PMB Tampon Collection Women ≥45 years of age, presenting with abnormal uterine bleeding (AUB) or post-menopausal bleeding (PMB). These presenting symptoms clinically warrant evaluation such as an endometrial biopsy to assess for underlying endometrial cancer, endometrial hyperplasia or other endometrial pathology. Cohort 3 - Cervix pathology Tampon Collection Women ≥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. Cohort 4 - Benign Uterine Pathology Tampon Collection Women with any of four benign gynecologic conditions including: uterine fibroids, benign endometrial polyps, adenomyosis and endometriosis. All women 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. Cohort 5 - Healthy Control Women Tampon Collection Healthy women ≥45 years of age presenting for well-woman exams to serve as a control group. These women will have no clinically evident gynecologic precancers, gynecologic cancers, or clinically evident or symptomatic benign gynecologic conditions. These women 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. Cohort 7 - OC Cohort - Biopsy proven or clinically suspected ovarian cancer (OC) Tampon Collection Women ≥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.
- 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 tampon-collected 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 collected via intravaginal tampon. 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 tampon-collected 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 collected via intravaginal tampon. 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 tampon-based 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 (15)
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
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
The Woman's Health Pavilion
🇺🇸Westbury, New York, United States
Altru Health System
🇺🇸Grand Forks, North Dakota, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Medical Colleagues of Texas, LLP
🇺🇸Katy, Texas, United States