Clinical trial NCT04491643: Megestrol Acetate Plus Rosuvastatin in Young Women with Early Endometrial Carcinoma
Official title: Megestrol Acetate Plus Rosuvastatin in Young Women with Early Endometrial Carcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Endometrial Carcinoma Stage I
Keywords: megestrol acetate
rosuvastatin
endometrial carcinoma stage I limited to endometrium
conservative treatment
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2020-07-29
Enrollment: 48
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Simon two-stage optimal design
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: 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:

  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 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)

Primary outcomes:
measure: Pathological response rate
timeFrame: 12 to 16 weeks
Secondary outcomes:
measure: Pathological response rate
timeFrame: 28 to 32 weeks
measure: Pathological response duration
timeFrame: up to 2 years
measure: Pathological response rate classified by different blood lipid level
timeFrame: up to 32 weeks
measure: Toxicity evaluation
timeFrame: up to 32 weeks
measure: Relapse rate
timeFrame: Up to 2 years after the end of treatment
measure: Pregnancy rate
timeFrame: Up to 2 years after the end of treatment
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Obstetrics and Gynecology Hospital, Fudan University
Study officials:
affiliation: Obstetrics and Gynecology Hospital, Fudan University
name: Xiaojun Chen, PhD
role: PRINCIPAL_INVESTIGATOR
References: