Endometrial HyperplasiaPhase 3NCT04897217
Levonorgestrel-Releasing Intrauterine System (LNG-IUS) in the Management of Atypical Endometrial Hyperplasia
A Phase 3 study testing Megestrol Acetate and Levonorgestrel Drug Implant in people with Endometrial Hyperplasia, run by Wake Forest University Health Sciences.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Endometrial Hyperplasia
- What is being tested?
- Megestrol Acetate and Levonorgestrel Drug Implant
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 30 Jun 2023to Nov 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
About this study
Official title: 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.
Read the 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.
- Conditions
- Endometrial Hyperplasia
- Being tested
- Megestrol Acetate, Levonorgestrel Drug Implant
- Medical subject headings
- Endometrial Hyperplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Megestrol AcetateDrug
The control arm will consist of oral progesterone therapy (megestrol acetate 160mg po daily). The intervention will be administered on an outpatient basis.
Levonorgestrel Drug ImplantDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Megestrol Acetate Arm - Control Arm | Active comparator | Megestrol Acetate 160 mg by mouth daily Receives: Drug: Megestrol Acetate |
| Levonorgestrel IUD - Comparison Arm | Experimental | Levonorgestrel intrauterine device with 52 mg progestin (Releases 20mcg/daily) Receives: Drug: Levonorgestrel Drug Implant |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (2)
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.
Measured: Up to 8 months
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.
Measured: Up to 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2021
- Study start30 Jun 2023 (estimated)
- Primary completionOct 2024 (estimated)
- Study completionNov 2026 (estimated)
Why it stopped: PI decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Endometrial HyperplasiaStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Janelle Darby, MD, Principal investigator, Wake Forest Baptist Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04897217
- Sponsor's protocol ID
- IRB00074615
- Other IDs
- WFBCCC 99321, P30CA012197
- Status last verified
- Jul 2023
- First submitted
- 17 May 2021
- Last updated
- 5 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Levonorgestrel-Releasing Intrauterine System (LNG-IUS) in the Management of Atypical Endometrial Hyperplasia: A Non-Inferiority Study
- ClinicalTrials.gov ID
- NCT04897217
- Acronym / sponsor ID
- IRB00074615
- Conditions
- Endometrial Hyperplasia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: PI decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 30 Jun 2023 (estimated)
- Primary completion
- Oct 2024 (estimated)
- Study completion
- Nov 2026 (estimated)
- First posted
- 21 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Megestrol Acetate Arm - Control Arm | Active comparator | Drug: Megestrol AcetateMegestrol Acetate 160 mg by mouth daily |
| Levonorgestrel IUD - Comparison Arm | Experimental | Drug: Levonorgestrel Drug ImplantLevonorgestrel intrauterine device with 52 mg progestin (Releases 20mcg/daily) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Megestrol AcetateThe control arm will consist of oral progesterone therapy (megestrol acetate 160mg po daily). The intervention will be administered on an outpatient basis. | Drug | Megestrol Acetate Arm - Control Arm |
| Levonorgestrel Drug ImplantParticipants 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. | Drug | Levonorgestrel IUD - Comparison Arm |
Primary outcome
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.
2 secondary outcomes
Number of Toxicities for Each Treatment
Time frame: Up to 8 months
Pathological Response to Treatment
Time frame: Up to 8 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2023.
- Individual participant dataSharing planned: No
Related trials for Endometrial Hyperplasia
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Not yet recruitingPhase 2
Canagliflozin Plus Progestin for Atypical Endometrial Hyperplasia and Early-Stage Endometrial Cancer
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RecruitingPhase 2
A Study to Estimate Early Clinical Efficacy Signals of GLP-1 Agonist Administration in Conjunction With Levonorgestrel Intrauterine Device in Obese Patients With Endometrioid Intraepithelial Neoplasia
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janelle Darby, MD principal investigator
Wake Forest Baptist Health Sciences
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Megestrol Acetate and Levonorgestrel Drug Implant in people with Endometrial Hyperplasia, run by Wake Forest University Health Sciences.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 5 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Histologic Response Scoring of Biopsy Specimens (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2023.