Megestrol Acetate Plus Rosuvastatin in Young Women With Early Endometrial Carcinoma

Study Overview
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Brief Summary
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To explore the treatment efficacy of megestrol acetate plus rosuvastatin in patients with early endometrial carcinoma (EEC) seeking for conservative treatment.

Detailed Description
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After diagnosed of EEC by hysteroscopy, patients meet the study criteria 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 will receive MA (megestrol acetate) 160 mg by mouth daily 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 hyperplasia with or without atypic; stable disease (SD) is defined as the persistence of the disease; and progressive disease (PD) is defined as the appearance of higher pathological progression, or myometrial invasion, or extra-uterine metastasis. Continuous therapies will be needed in PR or NR. Patients with PD will be recommended for hysterectomy. Due to personal reasons, patients may not accept hysteroscopic evaluation every three months, then the longest duration will be 8 months. For patients remained SD after 6 to 8 months of treatment but refused hysterectomy, a multiple disciplinary discussion would be held for individual case, and alternative treatment would be given. Two months of maintenance treatment will be recommended for patients with CR, and participants will be followed up for 2 years.

Official Title
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Megestrol Acetate Plus Rosuvastatin in Young Women With Early Endometrial Carcinoma

Conditions
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Endometrial Carcinoma Stage I

Intervention / Treatment
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* Drug: Megestrol Acetate
* Drug: Rosuvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a confirmed pathological diagnosis based upon hysteroscopy: histologically prove well-differentiated EEC G1 without myometrial invasion No signs of suspicious extrauterine involvement on enhanced magnetic resonance imaging (MRI) or enhanced computed tomography (CT) or ultrasound 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 atorvastatin 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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Simon two-stage optimal design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MA + Rosuvastatin<br>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, patients may not accept hysteroscopic evaluation every three months, then the longest duration will be 8 months. | Drug: Megestrol Acetate<br>* At a dosage of 160 mg/day<br>Drug: Rosuvastatin<br>* At a dosage of 10 mg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological response rate | From date of initial therapy until the date of CR or date of hysterectomy, whichever come first, assessed up to 16 weeks. | 12 to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological response rate | From date of initial therapy until the date of CR or date of hysterectomy, whichever come first, assessed up to 32 weeks. | 28 to 32 weeks | 
| Pathological response duration | Pathological response duration | up to 2 years | 
| Pathological response rate classified by different blood lipid level | Pathological response rate classified by different blood lipid level | up to 32 weeks | 
| Toxicity evaluation | Toxicity evaluation according to CTCAE 5.0 version. | up to 32 weeks | 
| Relapse rate |  | Up to 2 years after the end of treatment | 
| Pregnancy rate |  | Up to 2 years after the end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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megestrol acetate, rosuvastatin, endometrial carcinoma stage I limited to endometrium, conservative treatment