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

July 3, 2023 updated by: Wake Forest University Health Sciences

Levonorgestrel-Releasing Intrauterine System (LNG-IUS) in the Management of Atypical Endometrial Hyperplasia: A Non-Inferiority Study

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Primary Objective: To determine if Levonorgestrel-releasing intrauterine system is of equal efficacy to the standard systemic progestin therapy (megestrol acetate) based on endometrial sampling at 6 months after randomization. Non-inferiority analysis.

Secondary Objective(s):

  • To determine the safety of each treatment modality.
  • Determine the feasibility of transvaginal ultrasound to predict treatment response.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Wake Forest Baptist Health Sciences
        • Contact:
        • Principal Investigator:
          • Janelle Darcy, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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).
  • Endometrial carcinoma (worrisome or possible carcinoma not exclusionary but requires dilatation and curettage if based only on office biopsy).
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Megestrol Acetate Arm - Control Arm
Megestrol Acetate 160 mg by mouth daily
Drug: Megestrol Acetate
The control arm will consist of oral progesterone therapy (megestrol acetate 160mg po daily). The intervention will be administered on an outpatient basis.
Experimental: Levonorgestrel IUD - Comparison Arm
Levonorgestrel intrauterine device with 52 mg progestin (Releases 20mcg/daily)
Drug: Levonorgestrel Drug Implant
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Histologic Response Scoring of Biopsy Specimens
Time Frame: 6 months
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Toxicities for Each Treatment
Time Frame: Up to 8 months
Toxicities for each treatment modality based on standard toxicity scoring using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Investigators will compare the number of toxicities between the two treatment groups using chi-squared tests.
Up to 8 months
Pathological Response to Treatment
Time Frame: Up to 8 months
The pathological response variable will be treated as a binary variable, the Wilcoxon rank sum test will be used to explore the association between measurement of the endometrial stripe and the response outcome at each visit. 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.
Up to 8 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Wake Forest University Health Sciences

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Janelle Darby, MD, Wake Forest Baptist Health Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 30, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 17, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 20, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 21, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 5, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 3, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB00074615
  • P30CA012197 (U.S. NIH Grant/Contract)
  • WFBCCC 99321 (Other Identifier: Wake Forest Baptist Comprehensive Cancer Center)

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

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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