Megestrol Acetate Plus Rosuvastatin in Young Women With Atypical Endometrial Hyperplasia

Phase 2

Completed

• Conditions: Atypical Endometrial Hyperplasia
• Interventions: Drug: Megestrol Acetate; Drug: Rosuvastatin

• Registration Number: NCT04491682
• Lead Sponsor: Fudan University

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.

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 Timeline

• Study First Submitted: 2020-06-21
• Study First Submitted QC: 2020-07-27
• Study First Posted: 2020-07-29
• Study Start: 2020-09-01
• Primary Completion: 2022-06-20
• Study Completion: 2022-06-20
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-26
• Last Update Posted: 2024-01-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 36

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:

  1. Total cholesterol (TC) ≥ 5.2mmol/L (200mg/dL)
  2. Low-density lipoprotein cholesterol (LDL-C) ≥ 3.4mmol/L (130mg/dL)
  3. Fasting triglycerides (TG) ≥ 1.7mmol/L (150mg/dL)
  4. High-density lipoprotein cholesterol (HDL-C) < 1.03mmol/L (40mg/dL)
  5. 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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MA + Rosuvastatin	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.
MA + Rosuvastatin	Megestrol Acetate	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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
Pregnancy rate	up to 2 years after the therapy for each patient

Trial Locations

Locations (1)

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