Atypical Endometrial HyperplasiaPhase 2/3NCT03241888
Megestrol Acetate Plus LNG-IUS in Young Women With Endometrial Atypical Hyperplasia
A Phase 2/3 study testing Megestrol Acetate and Levonorgestrel-releasing Intrauterine System(LNG-IUS) in people with Atypical Endometrial Hyperplasia, run by Fudan University at 1 site in China.
Trial summary
To see if megestrol acetate plus Levonorgestrel-releasing intrauterine system (LNG-IUS) will not be inferior to returning the endometrial tissue to a normal state than megestrol acetate or LNG-IUS alone in patients with endometrial atypical hyperplasia. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Atypical Endometrial Hyperplasia
- What is being tested?
- Megestrol Acetate and Levonorgestrel-releasing Intrauterine System(LNG-IUS)
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 1 siteChina
- Study dates
- 4 Jul 2017to 18 Jun 2020
- Phase
- Phase 2/3
- 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 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Primarily have a confirmed diagnosis of endometrial atypical hyperplasia based upon hysteroscopy
- Have a desire for remaining reproductive function or uterus
- Need to be able to undergo correlative treatment and follow-up
Who cannot join
- Acute liver disease or liver tumor (benign or malignant) or renal dysfunction
- Pregnancy or suspicion of pregnancy
- Have a history of EAH and have disease relapse during Merina insertion
- Under treatment of high-dose progestin therapy more than 3 months in recent 6 months
- Congenital or acquired uterine anomaly including fibroids if they distort the uterine cavity
- Confirmed diagnosis of malignant tumor in genital system
Show all 10Show fewer
- Acute severe disease such as stroke or heart infarction or a history of thrombosis disease
- Hypersensitivity or contradiction to any component of this product
- Ask for removal of the uterus or other conservative treatment
- Smoker(>15 cigarettes a day)
Trial locations and contacts
1 site in 1 country.
China1 site
Obstetrics and Gynecology Hospital, Fudan University
Shanghai, Shanghai Municipality, 200011
About this study
Official title: Megestrol Acetate Plus LNG-IUS to Megestrol Acetate or LNG-IUS in Young Women With Endometrial Atypical Hyperplasia
To see if megestrol acetate plus Levonorgestrel-releasing intrauterine system (LNG-IUS) will not be inferior to returning the endometrial tissue to a normal state than megestrol acetate or LNG-IUS alone in patients with endometrial atypical hyperplasia.
Read the detailed description
After diagnosed of endometrial atypical hyperplasia (EAH) by hysteroscopy, patients will be enrolled. Age, waist circumstances, blood pressure, basic history of infertility, blood pressure, serum lipid level and side effects will be collected. Blood tests, including fasting blood glucose (FBG), postprandial blood glucose (PBG), fasting insulin (FINS), SHBG, sex hormone levels, blood lipids and anti-müllerian hormone(AMH) will be performed before treatment to evacuate their metabolic conditions.
Patients are randomized to 1 of 3 treatment groups. Patients will receive MA (megestrol acetate) 160 mg by mouth daily for at least 3 months on Arm I. Patients will receive LNG-IUS insertion on Arm II and MA 160 mg plus LNG-IUS insertion on Arm III. Then an hysteroscope will be used to evaluate the endometrial condition every 3 months, and the findings will be recorded. For patients with EAH, complete response (CR) is defined as the reversion of endometrial atypical hyperplasia to proliferative or secretory endometrium; partial response (PR) is defined as regression to simple or complex hyperplasia without atypia; no response (NR) is defined as the persistence of the disease; and progressive disease (PD) is defined as the appearance of endometrial cancer in patients. Continuous therapies will be needed in PR, NR or PD.
After completion of study treatment, 2 months of maintenance treatment will be recommended for patients with CR, and participants will be followed up for 2 years.
- Conditions
- Atypical Endometrial Hyperplasia
- Being tested
- Megestrol Acetate, Levonorgestrel-releasing Intrauterine System(LNG-IUS)
- Keywords
- Levonorgestrel-releasing intrauterine system, megestrol acetate, Atypical Endometrial Hyperplasia
- 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
Also called Megace
At a dosage of 160 mg/day
Levonorgestrel-releasing Intrauterine System(LNG-IUS)Device
Also called Mirena Intrauterine Device, Mirena
Active ingredient: levonorgestrel 52mg. It is a hormone-releasing T-shaped intrauterine system.
| Study group | Role | What they receive |
|---|---|---|
| MA | Active comparator | Patients will receive megestrol acetate 160 mg by mouth daily for at least 3 months.Then every 3 months, an hysteroscope will be used to evaluate the endometrial condition, and the findings will be recorded. Receives: Drug: Megestrol Acetate |
| LNG-IUS | Active comparator | Patients will receive LNG-IUS insertion for at least 3 months. Then every 3 months, an hysteroscope will be used to evaluate the endometrial condition, and the findings will be recorded. Receives: Device: Levonorgestrel-releasing Intrauterine System(LNG-IUS) |
| MA+LNG-IUS | Experimental | Patients will receive MA (160mg po qd) plus LNG-IUS insertion for at least 3 months. Then every 3 months, an hysteroscope will be used to evaluate the endometrial condition, and the findings will be recorded. Receives: Drug: Megestrol Acetate; Device: Levonorgestrel-releasing Intrauterine System(LNG-IUS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological response rate
the proportion of histologic regression from endometrial atypical hyperplasia to benign endometrium
Measured: From date of randomization until the date of CR or date of hysterectomy, whichever came first, assessed up to 12 months
Pathological response time
time of histologic regression from endometrial atypical hyperplasia to benign endometrium
Measured: From date of randomization until the date of CR or date of hysterectomy, whichever came first, assessed up to 12 months
Secondary outcomes (4)
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Common side effects from these drugs include weight gain, vaginal spotting and descent of sexuality. Severe side effects include thrombus and diseases related. The investigators will record any mental or body symptoms and evaluate the correlation.
Measured: up to 2 years after the treatment for each patient
Rate of relapse
the proportion of experiencing recurrence after regression
Measured: up to 2 years after the treatment for each patient
Rate of pregnancy
the proportion of getting pregnancy after regression
Measured: up to 2 years after the treatment for each patient
Compliance
The investigators designed a questionnaire to evaluate the compliance through treatment as side effects of oral megestrol acetate may be more common than LNG-IUS. Self Efficacy, physical activity and social support will be scored (1 to 5) and compared among each arm.
Measured: up to 2 years after the treatment for each patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2017
- Study start4 Jul 2017
- Primary completion18 Jun 2020
- Study completion18 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Atypical Endometrial HyperplasiaStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xiaojun Chen, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03241888
- Sponsor's protocol ID
- 2017-30-1
- Status last verified
- Sep 2024
- First submitted
- 12 Jul 2017
- Last updated
- 26 Sep 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study data are available after a request email with indications.
Publications
Gressel GM, Parkash V, Pal L. Management options and fertility-preserving therapy for premenopausal endometrial hyperplasia and early-stage endometrial cancer. Int J Gynaecol Obstet. 2015 Dec;131(3):234-9. doi: 10.1016/j.ijgo.2015.06.031. Epub 2015 Sep 8.
PubMed 26384790Park JY, Kim DY, Kim JH, Kim YM, Kim KR, Kim YT, Seong SJ, Kim TJ, Kim JW, Kim SM, Bae DS, Nam JH. Long-term oncologic outcomes after fertility-sparing management using oral progestin for young women with endometrial cancer (KGOG 2002). Eur J Cancer. 2013 Mar;49(4):868-74. doi: 10.1016/j.ejca.2012.09.017. Epub 2012 Oct 13.
PubMed 23072814Orbo A, Vereide A, Arnes M, Pettersen I, Straume B. Levonorgestrel-impregnated intrauterine device as treatment for endometrial hyperplasia: a national multicentre randomised trial. BJOG. 2014 Mar;121(4):477-86. doi: 10.1111/1471-0528.12499. Epub 2013 Nov 28.
PubMed 24286192Wildemeersch D, Janssens D, Pylyser K, De Wever N, Verbeeck G, Dhont M, Tjalma W. Management of patients with non-atypical and atypical endometrial hyperplasia with a levonorgestrel-releasing intrauterine system: long-term follow-up. Maturitas. 2007 Jun 20;57(2):210-3. doi: 10.1016/j.maturitas.2006.12.004. Epub 2007 Jan 31.
PubMed 17270370Montz FJ, Bristow RE, Bovicelli A, Tomacruz R, Kurman RJ. Intrauterine progesterone treatment of early endometrial cancer. Am J Obstet Gynecol. 2002 Apr;186(4):651-7. doi: 10.1067/mob.2002.122130.
PubMed 11967486Chen M, Jin Y, Li Y, Bi Y, Shan Y, Pan L. Oncologic and reproductive outcomes after fertility-sparing management with oral progestin for women with complex endometrial hyperplasia and endometrial cancer. Int J Gynaecol Obstet. 2016 Jan;132(1):34-8. doi: 10.1016/j.ijgo.2015.06.046. Epub 2015 Oct 1.
PubMed 26493012Xu Z, Yang B, Shan W, Liao J, Shao W, Wu P, Zhou S, Ning C, Luo X, Zhu Q, Zhang H, Ma F, Guan J, Chen X. Comparison of the effect of levonorgestrel-intrauterine system with or without oral megestrol acetate on fertility-preserving treatment in patients with atypical endometrial hyperplasia: A prospective, open-label, randomized controlled phase II study. Gynecol Oncol. 2023 Jul;174:133-141. doi: 10.1016/j.ygyno.2023.05.001. Epub 2023 May 12.
PubMed 37182434Mittermeier T, Farrant C, Wise MR. Levonorgestrel-releasing intrauterine system for endometrial hyperplasia. Cochrane Database Syst Rev. 2020 Sep 6;9(9):CD012658. doi: 10.1002/14651858.CD012658.pub2.
PubMed 32909630
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Megestrol Acetate Plus LNG-IUS to Megestrol Acetate or LNG-IUS in Young Women With Endometrial Atypical Hyperplasia
- ClinicalTrials.gov ID
- NCT03241888
- Acronym / sponsor ID
- 2017-30-1
- Conditions
- Atypical Endometrial Hyperplasia
- Keywords
- Levonorgestrel-releasing intrauterine system, megestrol acetate, Atypical Endometrial Hyperplasia
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 4 Jul 2017 (actual)
- Primary completion
- 18 Jun 2020 (actual)
- Study completion
- 18 Jun 2020 (actual)
- First posted
- 8 Aug 2017 (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.
To see if megestrol acetate plus Levonorgestrel-releasing intrauterine system (LNG-IUS) will not be inferior to returning the endometrial tissue to a normal state than megestrol acetate or LNG-IUS alone in patients with endometrial atypical hyperplasia.
Detailed description
After diagnosed of endometrial atypical hyperplasia (EAH) by hysteroscopy, patients will be enrolled. Age, waist circumstances, blood pressure, basic history of infertility, blood pressure, serum lipid level and side effects will be collected. Blood tests, including fasting blood glucose (FBG), postprandial blood glucose (PBG), fasting insulin (FINS), SHBG, sex hormone levels, blood lipids and anti-müllerian hormone(AMH) will be performed before treatment to evacuate their metabolic conditions.
Patients are randomized to 1 of 3 treatment groups. Patients will receive MA (megestrol acetate) 160 mg by mouth daily for at least 3 months on Arm I. Patients will receive LNG-IUS insertion on Arm II and MA 160 mg plus LNG-IUS insertion on Arm III. Then an hysteroscope will be used to evaluate the endometrial condition every 3 months, and the findings will be recorded. For patients with EAH, complete response (CR) is defined as the reversion of endometrial atypical hyperplasia to proliferative or secretory endometrium; partial response (PR) is defined as regression to simple or complex hyperplasia without atypia; no response (NR) is defined as the persistence of the disease; and progressive disease (PD) is defined as the appearance of endometrial cancer in patients. Continuous therapies will be needed in PR, NR or PD.
After completion of study treatment, 2 months of maintenance treatment will be recommended for patients with CR, and participants will be followed up for 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MA | Active comparator | Drug: Megestrol AcetatePatients will receive megestrol acetate 160 mg by mouth daily for at least 3 months.Then every 3 months, an hysteroscope will be used to evaluate the endometrial condition, and the findings will be recorded. |
| LNG-IUS | Active comparator | Device: Levonorgestrel-releasing Intrauterine System(LNG-IUS)Patients will receive LNG-IUS insertion for at least 3 months. Then every 3 months, an hysteroscope will be used to evaluate the endometrial condition, and the findings will be recorded. |
| MA+LNG-IUS | Experimental | Drug: Megestrol Acetate, Device: Levonorgestrel-releasing Intrauterine System(LNG-IUS)Patients will receive MA (160mg po qd) plus LNG-IUS insertion for at least 3 months. Then every 3 months, an hysteroscope will be used to evaluate the endometrial condition, and the findings will be recorded. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Primarily have a confirmed diagnosis of endometrial atypical hyperplasia based upon hysteroscopy
- Have a desire for remaining reproductive function or uterus
- Need to be able to undergo correlative treatment and follow-up
Key exclusion criteria (10 listed)
- Acute liver disease or liver tumor (benign or malignant) or renal dysfunction
- Pregnancy or suspicion of pregnancy
- Have a history of EAH and have disease relapse during Merina insertion
- Under treatment of high-dose progestin therapy more than 3 months in recent 6 months
- Congenital or acquired uterine anomaly including fibroids if they distort the uterine cavity
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 AcetateAlso: MegaceAt a dosage of 160 mg/day | Drug | MA, MA+LNG-IUS |
| Levonorgestrel-releasing Intrauterine System(LNG-IUS)Also: Mirena Intrauterine Device, MirenaActive ingredient: levonorgestrel 52mg. It is a hormone-releasing T-shaped intrauterine system. | Device | LNG-IUS, MA+LNG-IUS |
Primary outcome
Pathological response rate
Time frame: From date of randomization until the date of CR or date of hysterectomy, whichever came first, assessed up to 12 months
the proportion of histologic regression from endometrial atypical hyperplasia to benign endometrium
Pathological response time
Time frame: From date of randomization until the date of CR or date of hysterectomy, whichever came first, assessed up to 12 months
time of histologic regression from endometrial atypical hyperplasia to benign endometrium
4 secondary outcomes
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: up to 2 years after the treatment for each patient
Rate of relapse
Time frame: up to 2 years after the treatment for each patient
Rate of pregnancy
Time frame: up to 2 years after the treatment for each patient
Compliance
Time frame: up to 2 years after the treatment for each patient
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2024.
- Background: PubMed 26384790Gressel GM, Parkash V, Pal L. Management options and fertility-preserving therapy for premenopausal endometrial hyperplasia and early-stage endometrial cancer. Int J Gynaecol Obstet. 2015 Dec;131(3):234-9. doi: 10.1016/j.ijgo.2015.06.031. Epub 2015 Sep 8.
- Background: PubMed 23072814Park JY, Kim DY, Kim JH, Kim YM, Kim KR, Kim YT, Seong SJ, Kim TJ, Kim JW, Kim SM, Bae DS, Nam JH. Long-term oncologic outcomes after fertility-sparing management using oral progestin for young women with endometrial cancer (KGOG 2002). Eur J Cancer. 2013 Mar;49(4):868-74. doi: 10.1016/j.ejca.2012.09.017. Epub 2012 Oct 13.
- Background: PubMed 24286192Orbo A, Vereide A, Arnes M, Pettersen I, Straume B. Levonorgestrel-impregnated intrauterine device as treatment for endometrial hyperplasia: a national multicentre randomised trial. BJOG. 2014 Mar;121(4):477-86. doi: 10.1111/1471-0528.12499. Epub 2013 Nov 28.
- Background: PubMed 17270370Wildemeersch D, Janssens D, Pylyser K, De Wever N, Verbeeck G, Dhont M, Tjalma W. Management of patients with non-atypical and atypical endometrial hyperplasia with a levonorgestrel-releasing intrauterine system: long-term follow-up. Maturitas. 2007 Jun 20;57(2):210-3. doi: 10.1016/j.maturitas.2006.12.004. Epub 2007 Jan 31.
- Background: PubMed 11967486Montz FJ, Bristow RE, Bovicelli A, Tomacruz R, Kurman RJ. Intrauterine progesterone treatment of early endometrial cancer. Am J Obstet Gynecol. 2002 Apr;186(4):651-7. doi: 10.1067/mob.2002.122130.
- Background: PubMed 26493012Chen M, Jin Y, Li Y, Bi Y, Shan Y, Pan L. Oncologic and reproductive outcomes after fertility-sparing management with oral progestin for women with complex endometrial hyperplasia and endometrial cancer. Int J Gynaecol Obstet. 2016 Jan;132(1):34-8. doi: 10.1016/j.ijgo.2015.06.046. Epub 2015 Oct 1.
- Derived from this study: PubMed 37182434Xu Z, Yang B, Shan W, Liao J, Shao W, Wu P, Zhou S, Ning C, Luo X, Zhu Q, Zhang H, Ma F, Guan J, Chen X. Comparison of the effect of levonorgestrel-intrauterine system with or without oral megestrol acetate on fertility-preserving treatment in patients with atypical endometrial hyperplasia: A prospective, open-label, randomized controlled phase II study. Gynecol Oncol. 2023 Jul;174:133-141. doi: 10.1016/j.ygyno.2023.05.001. Epub 2023 May 12.
- Derived from this study: PubMed 32909630Mittermeier T, Farrant C, Wise MR. Levonorgestrel-releasing intrauterine system for endometrial hyperplasia. Cochrane Database Syst Rev. 2020 Sep 6;9(9):CD012658. doi: 10.1002/14651858.CD012658.pub2.
- Individual participant dataSharing planned: Yes. Study data are available after a request email with indications.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Megestrol Acetate and Levonorgestrel-releasing Intrauterine System(LNG-IUS) in people with Atypical Endometrial Hyperplasia, run by Fudan University at 1 site in China.
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 3 inclusion and 10 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: finished, as of the sponsor's last update on 26 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Pathological response rate (time frame: From date of randomization until the date of CR or date of hysterectomy, whichever came first, assessed up to 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03241888, which also lists 8 linked publications.
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 26 Sep 2024.