Metformin Plus Megestrol Acetate as a Fertility-sparing Treatment in Patients With Atypical Endometrial Hyperplasia

Comparing Metformin Plus Megestrol Acetate With Megestrol Acetate Alone as a Fertility-sparing Treatment in Patients With Atypical Endometrial Hyperplasia

To verify whether metformin could improve the effect of progestin as fertility-sparing treatment in patients with atypical endometrial hyperplasia(AEH).

Study Overview

• Status: Terminated
• Conditions: Atypical Endometrial Hyperplasia
• Intervention / Treatment: Drug: Metformin plus Megestrol acetate; Drug: Megestrol Acetate

Detailed Description

Whether metformin could improve the effect of progestin as fertility-sparing treatment in patients with atypical endometrial hyperplasia(AEH) is still not clear. Our previous finding from subgroup analysis in a phase II randomized controlled trial showed that 39.6% of AEH patients in metformin plus megestrol acetate group achieved complete response, compared with 20.4% in group of megestrol acetate alone. This trial aim to fully testify the effect of metformin in fertility-sparing treatment for AEH patients with adequate sample size.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200011
      • Obstetrics and Gynecology Hospital, Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. 18-45 years old;
2. pathologically diagnosed with AEH for the first time;
3. desire to preserve their fertility;
4. no signs of suspicious myometrial invasion or extrauterine metastasis by enhanced magnetic resonance imaging (MRI), enhanced computed tomography (CT) or transvaginal ultrasonography (TVUS);
5. no contraindication for metformin, megestrol acetate or pregnancy;
6. no hormone or metformin treatment within 6 months before entering the trial;
7. not pregnant when participating in the trial;
8. willing to follow the trial arrangement after being fully informed of all the risks and inconveniences caused by the trial.

Exclusion Criteria:

Patients who had one or more of the following conditions:

1. allergy history or contraindications for megestrol acetate or metformin;
2. pregnant when initiating the study;
3. alcoholism, severe infection, severe chronical diseases (dysfunction of heart, liver, lung or kidney);
4. high risk of thrombosis;
5. recurrent AEH;
6. endometrial cancer;
7. other malignancy history.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metformin plus megestrol acetate; Metformin 1500mg per day plus megestrol acetate 160mg per day.	Drug: Metformin plus Megestrol acetate; metformin 1500mg, per day, oral; megestrol acetate 160mg per day, oral
Active Comparator: Megestrol acetate; Megestrol acetate 160mg per day.	Drug: Megestrol Acetate; megestrol acetate 160mg per day, oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response within 16 weeks of treatment	reversion of AEH The reversion of AEH to proliferative or secretory endometrium	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response within 32 weeks of treatment	The reversion of AEH to proliferative or secretory endometrium	32 weeks
Adverse events	Adverse events during the treatment of metformin plus megestrol acetate or megestrol acetate alone	32 weeks
2-year recurrence rate	recurrence rate within 2 years after the treatment	2 years
2-year pregnancy rate	Pregnancy rate within 2 years after the treatment	2 years
2-year live-birth rate	Live-birth rate within 2 years after the treatment	2 years

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: XIAOJUN CHEN, PhD, Obstetrics & Gynecology Hospital of Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2021
• Primary Completion (Actual): June 3, 2021
• Study Completion (Actual): June 3, 2021

Study Registration Dates

• First Submitted: October 23, 2020
• First Submitted That Met QC Criteria: October 28, 2020
• First Posted (Actual): October 29, 2020

Study Record Updates

• Last Update Posted (Actual): April 5, 2022
• Last Update Submitted That Met QC Criteria: March 24, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Uterine Diseases; Hyperplasia; Endometrial Hyperplasia; Hypoglycemic Agents; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Central Nervous System Stimulants; Appetite Stimulants; Metformin; Megestrol; Megestrol Acetate
• Other Study ID Numbers: V01 2020-10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Data will be shared with other researchers without patients' personal information after all the findings being published.

Drug and device information, study documents

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