Megestrol Acetate Plus Rosuvastatin in Young Women With Atypical Endometrial Hyperplasia

Sponsor

Fudan University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04491682

Collaborator

(none)

Enrollment

Location

Arm

35.9

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To see if megestrol acetate plus rosuvastatin will be superior to reversing the endometrial lesion to a normal endometrium than megestrol acetate alone in patients with atypical endometrial hyperplasia (AEH). Considering the large sample size in RCT, we used Simon two-stage design.

Condition or Disease	Intervention/Treatment	Phase
Atypical Endometrial Hyperplasia	Drug: Megestrol Acetate Drug: Rosuvastatin	Phase 2/Phase 3

Detailed Description

After diagnosed of AEH by hysteroscopy, patients will be enrolled. Age, height, weight, waist circumstances, blood pressure, basic history of infertility and blood pressure will be collected. Blood tests, including fasting blood glucose (FBG), fasting insulin (FINS), OGTT 2h blood glucose and insulin, blood lipids, SHBG, sex hormone levels, anti-müllerian hormone(AMH), creatine kinase(CK) and renal/liver function tests will be performed before treatment to evacuate their basic conditions. Each subject will receive body fat testing by Inbody 520.

Patients are randomized to 1 of 2 treatment groups. Patients will receive MA 160 mg plus rosuvastatin 10mg by mouth daily for at least 6 months. Then hysteroscopy will be used to evaluate the endometrial condition every 3 months, and intra-operative findings will be recorded. 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 atypic; stable disease (SD) 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 or NR. Patients with PD will be recommended for hysterectomy.

Two 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

Anticipated Enrollment :

36 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Megestrol Acetate Plus Rosuvastatin in Young Women With Atypical Endometrial Hyperplasia

Actual Study Start Date :

Sep 1, 2020

Anticipated Primary Completion Date :

Aug 31, 2023

Anticipated Study Completion Date :

Aug 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MA + Rosuvastatin Patients will receive MA 160 mg and rosuvastatin 10 mg by mouth daily for at least 6 months.Then every 3 months, hysteroscopy will be used to evaluate the endometrial condition, and findings will be recorded. Due to personal reasons, it may not be possible to accept hysteroscopic evaluation every three months, then the longest duration will be 8 months.	Drug: Megestrol Acetate At a dosage of 160 mg/day Drug: Rosuvastatin At a dosage of 10 mg/day

Arm

Intervention/Treatment

Experimental: MA + Rosuvastatin

Patients will receive MA 160 mg and rosuvastatin 10 mg by mouth daily for at least 6 months.Then every 3 months, hysteroscopy will be used to evaluate the endometrial condition, and findings will be recorded. Due to personal reasons, it may not be possible to accept hysteroscopic evaluation every three months, then the longest duration will be 8 months.

Drug: Megestrol Acetate

At a dosage of 160 mg/day

Drug: Rosuvastatin

At a dosage of 10 mg/day

Outcome Measures

Primary Outcome Measures

Pathological response rate [12 to 16 weeks]
From date of randomization or initial therapy until the date of CR or date of hysterectomy, whichever come first, assessed up to 16 weeks.

Secondary Outcome Measures

Pathological response rate [28 to 32 weeks]
From date of randomization or initial therapy until the date of CR or date of hysterectomy, whichever come first, assessed up to 32 weeks.
Pathological response duration [Up to 2 years]
Pathological response duration
Pathological response rate classified by different blood lipid level [Up to 32 weeks]
Pathological response rate classified by different blood lipid level
Toxicity evaluation [Up to 32 weeks]
Toxicity evaluation according to CTCAE 5.0 version.
Relapse rate [up to 2 years after the therapy for each patient]
Pregnancy rate [up to 2 years after the therapy for each patient]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Have a confirmed pathological diagnosis based upon hysteroscopy
Have a desire for remaining reproductive function or uterus
Good compliance with adjunctive treatment and follow-up
Abnormal blood lipid. At least meet one of the following five items:

Total cholesterol (TC) ≥ 5.2mmol/L (200mg/dL)
Low-density lipoprotein cholesterol (LDL-C) ≥ 3.4mmol/L (130mg/dL)
Fasting triglycerides (TG) ≥ 1.7mmol/L (150mg/dL)
High-density lipoprotein cholesterol (HDL-C) <1.03mmol/L (40mg/dL)
Apo-lipoprotein-A (Apo-A) ≥ 1.0g/L

Exclusion Criteria:

Acute liver disease or liver tumor (benign or malignant) or renal dysfunction
Pregnancy or potential pregnancy
Under treatment of high-dose progestin therapy more than 1 months in recent 6 months
Confirmed diagnosis of any cancer in reproductive system
Acute severe disease such as stroke or heart infarction or a history of thrombosis disease
Hypersensitivity or contradiction for using MA or statins
Already diagnosed with hyperlipidemia and using lipid-lowering drugs
With other factors of reproductive dysfunction;
Strong request for uterine removal or other conservative treatment
Smoker (>15 cigarettes a day)
Drinker (>20 grams a day)