Levonorgestrel-Releasing Intrauterine System (LNG-IUS) in the Management of Atypical Endometrial Hyperplasia

NCT04897217 | Withdrawn Phase 3 FDA Drug

• 3 other identifiers: IRB00074615WFBCCC 99321P30CA012197
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this research study is to compare the uterus tissue of women who receive an intrauterine system to treat their endometrial hyperplasia with the uterine tissue of women who receive megestrol acetate to treat their hyperplasia. While both methods are commonly used in practice, investigators would like to see what effects each treatment has on uterine tissue.

Conditions

Endometrial Hyperplasia

Outcome Measures

Primary Outcomes (1)

• Histologic Response Scoring of Biopsy Specimens

  The primary outcome is a response score (0: no response, 1: incomplete response, 2: complete response): Score -1 will be assigned to specimens with progression of disease (ie. Endometrial carcinoma); Score 0 will be assigned to specimens with atypical hyperplasia; Score 1 will be assigned to specimens with benign hyperplasia and will be indicative partial response to therapy; Score 2 will be assigned to specimens without hyperplasia and will be indicative of complete response to therapy. All study cases will be reviewed by a pathologist and all cases will be scored following the standard 2014 WHO classification of endometrial hyperplasia. Investigators will compare the estimated 90% confidence interval (CI) of the levonorgestrel-releasing Intrauterine system versus the standard therapy from the noninferiority trial to a predefined margin.

  6 months

Secondary Outcomes (2)

• Number of Toxicities for Each Treatment

  Up to 8 months

• Pathological Response to Treatment

  Up to 8 months

Study Arms (2)

Megestrol Acetate Arm - Control Arm

ACTIVE COMPARATOR

Megestrol Acetate 160 mg by mouth daily

Drug: Megestrol Acetate

Levonorgestrel IUD - Comparison Arm

EXPERIMENTAL

Levonorgestrel intrauterine device with 52 mg progestin (Releases 20mcg/daily)

Drug: Levonorgestrel Drug Implant

Interventions

Megestrol Acetate DRUG

The control arm will consist of oral progesterone therapy (megestrol acetate 160mg po daily). The intervention will be administered on an outpatient basis.

Megestrol Acetate Arm - Control Arm

Levonorgestrel Drug Implant DRUG

Participants in the comparison arm will have a levonorgestrel intrauterine device placed in the office or in the operating room if the office procedure not tolerated or if they have not had a prior dilation and curettage.

Levonorgestrel IUD - Comparison Arm

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Women of all races and ethnicity who meet the eligibility criteria are eligible for this trial. Men are excluded from participation due to the site-specific nature of the disease being studied (endometrial hyperplasia).
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Complex atypical endometrial hyperplasia only. Confirmed by pathology report.
• Normal renal function and liver function tests.
• Age 18 or older.
• The effects of megestrol acetate on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because megestrol acetate is known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

You may not qualify if:

• Prior complex atypical endometrial hyperplasia or carcinoma.
• Prior hormone sensitive malignancy.\]
• Exogenous estrogen or progestin use presently or within the past 12 months.
• Standard contraindications to progestin therapy.
• Standard contraindications to intrauterine device use.
• Simple hyperplasia, complex hyperplasia without atypia (may be present in addition to atypical endometrial hyperplasia).
• Pregnant women are excluded from this study because megestrol acetate has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with megestrol acetate, breastfeeding should be discontinued if the mother is treated with megestrol acetate.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Endometrial Hyperplasia

Interventions

Megestrol Acetate

Condition Hierarchy (Ancestors)

Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Megestrol; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Janelle Darby, MD

  Wake Forest Baptist Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2021
• First Posted: May 21, 2021
• Study Start: June 30, 2023
• Primary Completion: October 1, 2024
• Study Completion (Estimated): November 1, 2026
• Last Updated: July 5, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share