Cancer Driving Mutations in Endometriosis Lesions and Development of Progesterone Resistance

Endometriosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03756480
• Other study ID #: IRB00188129
• Secondary ID: R01HD096147
• Status: Recruiting
• Start date: October 1, 2020
• Est. completion date: October 1, 2026

Study information

• Verified date: August 2023
• Source: Johns Hopkins University
• Contact: James Segars, MD, FACOG
• Phone: 410-614-2000
• Email: jsegars2[@]jhmi.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 135
• Est. completion date: October 1, 2026
• Est. primary completion date: October 1, 2026
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Endometrial Diseases
• Endometriosis
• Uterine Diseases

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale School of Medicine	New Haven	Connecticut

Sponsors (3)

Lead Sponsor	Collaborator
Johns Hopkins University	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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