Cancer Driving Mutations in Endometriosis Lesions and Development of Progesterone Resistance

Prospective Clinical Study of the Relationship Between Cancer Driving Mutations Found in Endometriotic Implants and the Development of Progesterone Resistance

This study will test the hypothesis that the molecular changes present in ectopic endometriosis lesions correlate with progesterone-resistant disease (using the criteria defined in this study) and are present in matched eutopic endometrium.

Study Overview

• Status: Active, not recruiting
• Conditions: Endometriosis; Endometrial Diseases

Detailed Description

Tissues from 100 patients with endometriosis will be analyzed with droplet digital PCR (ddPCR) targeted sequencing and responders (n=50) will be compared to non-responders (n=50) after controlling confounding factors.

From a subset of the 100 cases, whole exome sequencing (WES) and Methylation-Specific PCR (MSP)-based methylation profiling on microdissected epithelium and stroma will be performed in matched eutopic and ectopic tissues from 20 patients with known cancer-associated mutations or 20 controls.

• Study Type: Observational
• Enrollment (Estimated): 135

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale School of Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Johns Hopkins Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Women between the ages of 18-45 undergoing surgical management for endometriosis as cases and women between ages of 18-45 years undergoing elective tubal ligation and no diagnosis of endometriosis.

Description

Inclusion Criteria:

• Signed informed consent.
• Gender: female.
• Age: 18-45 years at the time of signing consent.
• Clinical or surgical diagnosis of endometriosis undergoing laparoscopy.
• Controls may not have clinical or surgical diagnosis of endometriosis.
• Regular menstrual cycles.
• BMI between 18-40 kg/m2.
• Sexually active or have had a previous vaginal exam that used a speculum.
• English speaking

Exclusion Criteria:

• Use of any kind of steroidal therapy including oral contraceptives, Norplant, estrogen replacement/supplemental therapy, androgens (Danazol, Cyclomen, Danocrine, testosterone) or progesterone. She may not be taking or be on Celebrex.
• Pregnant.
• Presence of pelvic infection.
• Mullerian anomalies with absence of a cervix.
• History of cancer of the reproductive tract.
• Presence of undiagnosed uterine bleeding.
• Treatment with intrauterine device (IUD) or progestin-containing intrauterine device.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Case Group; Clinical or surgical diagnosis of Endometriosis, patients undergoing surgical management 100 participants
Control Group; No diagnosis of Endometriosis, Patients undergoing Laparoscopic Tubal Ligation 35 participants

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of somatic cancer driver mutations in progesterone-resistant versus progesterone-sensitive endometriosis lesions.	Digital droplet PCR will be used to identify somatic cancer-driver mutations with the presence of at least one of KRAS or ARID1A or PIK3CA or PPP2R1A cancer-driver mutations to assess any difference between progesterone-resistant endometriosis and progesterone-sensitive endometriosis.	Six month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of cancer driver mutations in eutopic versus ectopic endometrial tissue in control versus diseased subjects	Whole exome sequencing in a subset of patients with progesterone-resistant disease and controls will be done using TruSeq Amplicon Cancer Panel (Illumina) to assess the number of cancer driver mutations.	Six month
Difference in DNA methylation PCR profile of endometriotic lesions in ectopic versus eutopic endometrium in control versus diseased subjects.	DNA methylation profile of eutopic and ectopic endometrial tissue for cases and controls will be done using Raw Illumina 450K methylation array to assess for any difference.	One month

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institutes of Health (NIH)
• Investigators: Principal Investigator: James Segars, MD, FACOG, Professor

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Actual): October 1, 2024
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: November 27, 2018
• First Submitted That Met QC Criteria: November 27, 2018
• First Posted (Actual): November 28, 2018

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Endometriosis
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Endometriosis; Uterine Diseases
• Other Study ID Numbers: IRB00188129; R01HD096147 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No