Medroxyprogesterone Acetate Plus Atorvastatin in Young Women With Early Endometrial Carcinoma and Atypical Endometrial Hyperplasia

Medroxyprogesterone Acetate Plus Atorvastatin in Young Women With Atypical Endometrial Hyperplasia and Early Endometrial Carcinoma

To explore the treatment efficacy of medroxyprogesterone acetate plus atorvastatin in patients with atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EEC) for conservative treatment.

Study Overview

• Status: Recruiting
• Conditions: Atypical Endometrial Hyperplasia; Endometrial Carcinoma Stage I
• Intervention / Treatment: Drug: Medroxyprogesterone acetate + Atorvastatin

Detailed Description

After diagnosed of AEH or EEC by hysteroscopy, patients meet the study criteria will be enrolled. The lipid content (lipid droplet, cholesterol and triglyceride) in endometrial lesion tissue was detected by Raman scattering instrument. And Age, height, weight, waistline, blood pressure, basic history of infertility and family cancer will be collected. Blood tests, including fasting blood glucose (FBG), fasting insulin (FINS), blood lipids, sex hormone levels, anti-müllerian hormone (AMH) and renal/liver function tests will be performed before treatment to evacuate their basic conditions. Each subject will receive body fat testing by Inbody 770.

Patients will receive MPA (Medroxyprogesterone acetate) 250-500 mg by mouth daily plus atorvastatin 20mg by mouth daily for at least 3 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. Patients with PD will be recommended for hysterectomy.

For patients remained SD after 9 months of treatment but refused hysterectomy, a multiple disciplinary discussion would be held for individual case, and alternative treatment would be given. Three months of maintenance treatment will be recommended for patients with CR, and participants will be followed up for at least 1 year.

• Study Type: Interventional
• Enrollment (Estimated): 82
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: HE YIJIAO, PhD; Phone Number: +8618301512017; Email: heyijiao2017@pku.edu.cn
• Study Contact Backup: Name: WANG JIANLIU, PHD/MD; Phone Number: +861088324383; Email: wangjianliu1203@163.com

Study Locations

• China
  • Beijing
    • Peking, Beijing, China, 100044
      • Recruiting
      • Wang Jianliu
      • Contact: WANG JIANLIU, PHD/MD; Phone Number: +861088324383; Email: wangjianliu1203@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have a confirmed pathological diagnosis based upon hysteroscopy: histologically prove AEH or well-differentiated EEC G1 without myometrial invasion: 1. Untreated patients; 2. Patients with persistent lesions after one course (12 weeks) of progesterone therapy; 3. Patients who did not achieve complete remission after 2 courses (24 weeks) of progesterone therapy;
• 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

Exclusion Criteria:

• Hypersensitivity or contradiction for using MPA or atorvastatin
• Pregnancy or potential pregnancy
• Confirmed diagnosis of any cancer in reproductive system
• Already diagnosed with hyperlipidemia and using lipid-lowering drugs
• Acute liver disease or liver tumor (benign or malignant) or renal dysfunction
• Acute severe disease such as stroke or heart infarction or a history of thrombosis disease
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; MPA + Atorvastatin	Drug: Medroxyprogesterone acetate + Atorvastatin; MPA (at a dosage of 250-500 mg/day,) + Atorvastatin (at a dosage of 20 mg/day), by mouth,
No Intervention: Control groups; MPA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological cumulative complete response rate;	3 to 4 months: From date of initial therapy until the date of CR or date of hysterectomy,	assessed up to 4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological cumulative complete response rate;	From 6 to 8 months; From date of initial therapy until the date of CR or date of hysterectomy,	assessed up to 8 months
Overall complete response rate	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 2 years;
Relapse rate	Relapse rate	up to 15 months after the end of treatment
Pregnancy rate	Pregnancy rate	up to 15 months after the end of treatment
Toxic Side Effect	Toxicity evaluation according to CTCAE 5.0 version.	up to 3 months after the end of treatment
The lipid content (lipid droplet, cholesterol and triglyceride) in endometrial lesion tissue	The lipid content (lipid droplet, cholesterol and triglyceride) in endometrial lesion	assessed up to 4 months

Collaborators and Investigators

• Sponsor: Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2023
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): October 31, 2025

Study Registration Dates

• First Submitted: December 29, 2022
• First Submitted That Met QC Criteria: December 29, 2022
• First Posted (Actual): January 9, 2023

Study Record Updates

• Last Update Posted (Actual): July 11, 2024
• Last Update Submitted That Met QC Criteria: July 9, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Endometrial Carcinoma; Atypical Endometrial Hyperplasia
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Carcinoma; Hyperplasia; Endometrial Hyperplasia; Endometrial Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Contraceptive Agents, Male; Atorvastatin; Medroxyprogesterone Acetate; Medroxyprogesterone
• Other Study ID Numbers: 2022PHB416

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No