Adnexal Mass, Atypical Endometrial Hyperplasia, Cervical Cancer, Cervical Dysplasia, Endometrial Cancer, Ovarian Cancer
Conditions
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.
Interventions
DIAGNOSTIC_TESTVaginal 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.
DIAGNOSTIC_TESTBlood Collection
A blood sample will be collected from each participant prior to undergoing any exams or procedures.
Sponsors
Mayo Clinic
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
for Cohort 1: 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)
Exclusion criteria
for Cohort 1: * 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 Inclusion Criteria for Cohort 2: 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
CONTACTMaureen A Lemens, BSN
CONTACTClinical Trials Referral Office
PRINCIPAL_INVESTIGATORJamie N. Bakkum-Gamez, M.D.
Mayo Clinic
Outcome results
None listed