Megestrol Acetate Plus LNG-IUS in Young Women With Endometrial Atypical Hyperplasia

Phase 2

Completed

• Conditions: Atypical Endometrial Hyperplasia
• Interventions: Device: Levonorgestrel-releasing Intrauterine System(LNG-IUS); Drug: Megestrol Acetate

• Registration Number: NCT03241888
• Lead Sponsor: Fudan University

Brief 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.

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 Timeline

• Study Start: 2017-07-04
• Study First Submitted: 2017-07-12
• Study First Submitted QC: 2017-08-05
• Study First Posted: 2017-08-08
• Status Verified: 2020-06
• Primary Completion: 2020-06-18
• Study Completion: 2020-06-18
• Last Update Submitted: 2020-06-18
• Last Update Posted: 2020-06-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 180

Inclusion Criteria

• 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

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Exclusion Criteria

• 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
• 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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LNG-IUS	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	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.
MA	Megestrol Acetate	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.
MA+LNG-IUS	Megestrol Acetate	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.

Primary Outcome Measures

Name	Time	Method
Pathological response rate	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	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

Secondary Outcome Measures

Name	Time	Method
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	up to 2 years after the treatment for each patient	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.
Rate of relapse	up to 2 years after the treatment for each patient	the proportion of experiencing recurrence after regression
Rate of pregnancy	up to 2 years after the treatment for each patient	the proportion of getting pregnancy after regression
Compliance	up to 2 years after the treatment for each patient	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.

Trial Locations

Locations (1)

Obstetrics and Gynecology Hospital, Fudan University; 🇨🇳 Shanghai, Shanghai, China