Cancer Driving Mutations in Endometriosis Lesions and Development of Progesterone Resistance

Recruiting

• Conditions: Endometriosis; Endometrial Diseases

• Registration Number: NCT03756480
• Lead Sponsor: Johns Hopkins University

Brief Summary

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.

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 Timeline

• Study First Submitted: 2018-11-27
• Study First Submitted QC: 2018-11-27
• Study First Posted: 2018-11-28
• Study Start: 2020-10-01
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-06
• Last Update Posted: 2024-08-07
• Primary Completion: 2026-10-01
• Study Completion: 2026-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 135

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Number of somatic cancer driver mutations in progesterone-resistant versus progesterone-sensitive endometriosis lesions.	Six month	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.

Secondary Outcome Measures

Name	Time	Method
Difference in DNA methylation PCR profile of endometriotic lesions in ectopic versus eutopic endometrium in control versus diseased subjects.	One month	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.
Number of cancer driver mutations in eutopic versus ectopic endometrial tissue in control versus diseased subjects	Six month	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.

Trial Locations

Locations (3)

Yale School of Medicine; 🇺🇸 New Haven, Connecticut, United States

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States