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

Sponsor

Fudan University (Other)

Overall Status

Completed

CT.gov ID

NCT03241888

Collaborator

Shanghai 6th People's Hospital (Other), Zhejiang Cancer Hospital (Other), Shanghai Changning Maternity & Infant Health Hospital (Other)

180

Enrollment

Location

Arms

35.5

Actual Duration (Months)

5.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atypical Endometrial Hyperplasia	Drug: Megestrol Acetate Device: Levonorgestrel-releasing Intrauterine System(LNG-IUS)	Phase 2/Phase 3

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

Study Type:

Interventional

Actual Enrollment :

180 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 4, 2017

Actual Primary Completion Date :

Jun 18, 2020

Actual Study Completion Date :

Jun 18, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: MA 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.	Drug: Megestrol Acetate At a dosage of 160 mg/day Other Names: Megace
Active Comparator: 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.	Device: Levonorgestrel-releasing Intrauterine System(LNG-IUS) Active ingredient: levonorgestrel 52mg. It is a hormone-releasing T-shaped intrauterine system. Other Names: Mirena Intrauterine Device Mirena
Experimental: MA+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.	Drug: Megestrol Acetate At a dosage of 160 mg/day Other Names: Megace Device: Levonorgestrel-releasing Intrauterine System(LNG-IUS) Active ingredient: levonorgestrel 52mg. It is a hormone-releasing T-shaped intrauterine system. Other Names: Mirena Intrauterine Device Mirena

Arm

Intervention/Treatment

Active Comparator: MA

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.

Drug: Megestrol Acetate

At a dosage of 160 mg/day

Other Names:

Megace

Active Comparator: 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.

Device: Levonorgestrel-releasing Intrauterine System(LNG-IUS)

Active ingredient: levonorgestrel 52mg. It is a hormone-releasing T-shaped intrauterine system.

Other Names:

Mirena Intrauterine Device

Mirena

Experimental: MA+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.

Drug: Megestrol Acetate

At a dosage of 160 mg/day

Other Names:

Megace

Device: Levonorgestrel-releasing Intrauterine System(LNG-IUS)

Active ingredient: levonorgestrel 52mg. It is a hormone-releasing T-shaped intrauterine system.

Other Names:

Mirena Intrauterine Device

Mirena

Outcome Measures

Primary Outcome Measures

Pathological response rate [From date of randomization until the date of CR or date of hysterectomy, whichever came first, assessed up to 12 months]
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

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]
Rate of pregnancy [up to 2 years after the treatment for each patient]
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.

Other Outcome Measures

Economic consequences through study completion [From date of randomization until the date of CR or date of hysterectomy, whichever came first, assessed up to 12 months]
The investigators will evaluate whether the combination could shorten the therapeutic period, so that bring economic benefits.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

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)