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

Primary Purpose

Endometrial Hyperplasia

Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Megestrol Acetate
Levonorgestrel Drug Implant
Sponsored by
Wake Forest University Health Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Endometrial Hyperplasia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Dilatation and curettage proven 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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Experimental

    Arm Label

    Megestrol Acetate Arm - Control Arm

    Levonorgestrel IUD - Comparison Arm

    Arm Description

    Megestrol Acetate 160 mg by mouth daily

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

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    Number of Toxicities for Each Treatment
    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.
    Pathological Response to Treatment
    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.

    Full Information

    First Posted
    May 17, 2021
    Last Updated
    July 3, 2023
    Sponsor
    Wake Forest University Health Sciences
    Collaborators
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04897217
    Brief Title
    Levonorgestrel-Releasing Intrauterine System (LNG-IUS) in the Management of Atypical Endometrial Hyperplasia
    Official Title
    Levonorgestrel-Releasing Intrauterine System (LNG-IUS) in the Management of Atypical Endometrial Hyperplasia: A Non-Inferiority Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2023
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    PI decision
    Study Start Date
    June 30, 2023 (Anticipated)
    Primary Completion Date
    October 2024 (Anticipated)
    Study Completion Date
    November 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Wake Forest University Health Sciences
    Collaborators
    National Cancer Institute (NCI)

    4. Oversight

    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
    Data Monitoring Committee
    No

    5. Study Description

    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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Endometrial Hyperplasia

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Megestrol Acetate Arm - Control Arm
    Arm Type
    Active Comparator
    Arm Description
    Megestrol Acetate 160 mg by mouth daily
    Arm Title
    Levonorgestrel IUD - Comparison Arm
    Arm Type
    Experimental
    Arm Description
    Levonorgestrel intrauterine device with 52 mg progestin (Releases 20mcg/daily)
    Intervention Type
    Drug
    Intervention Name(s)
    Megestrol Acetate
    Intervention Description
    The control arm will consist of oral progesterone therapy (megestrol acetate 160mg po daily). The intervention will be administered on an outpatient basis.
    Intervention Type
    Drug
    Intervention Name(s)
    Levonorgestrel Drug Implant
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Histologic Response Scoring of Biopsy Specimens
    Description
    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.
    Time Frame
    6 months
    Secondary Outcome Measure Information:
    Title
    Number of Toxicities for Each Treatment
    Description
    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.
    Time Frame
    Up to 8 months
    Title
    Pathological Response to Treatment
    Description
    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.
    Time Frame
    Up to 8 months

    10. Eligibility

    Sex
    Female
    Gender Based
    Yes
    Gender Eligibility Description
    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).
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Janelle Darby, MD
    Organizational Affiliation
    Wake Forest Baptist Health Sciences
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

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

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