Megestrol Acetate Plus Metformin to Megestrol Acetate in Patients With Endometrial Atypical Hyperplasia or Early Stage Endometrial Adenocarcinoma

September 10, 2021 updated by: Xiaojun Chen
The purpose of this study is to see if megestrol acetate plus metformin will be more effective in returning the endometrial tissue to a normal state than megestrol acetate alone in patients with endometrial atypical hyperplasia or early stage endometrial adenocarcinoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

After diagnosed of endometrial atypical hyperplasia(EAH) or type I endometrial cancer(EC) by dilatation and curettage (D&C) or hysteroscopy, patients will be enrolled. Age, waist circumstances, blood pressure, basic history of infertility, blood pressure, serum lipid level and side effects will be collected. Blood tests, including triglycerides, high density lipoprotein-cholesterol, fasting blood glucose, liver and kidney function will be performed before treatment to evacuate their metabolic conditions.

Patients are randomized to 1 of 2 treatment groups. Patients will receive metformin 500 mg by mouth third daily and megestrol acetate 160 mg by mouth daily for 3 months on Arm I. Patients will receive megestrol acetate 160 mg PO daily for 3 months on Arm II. Then an hysteroscope will be used to evaluate the endometrial condition, and the findings will be recorded. For patients with EAH, 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 atypia; no response (NR) is defined as the persistence of the disease; and progressive disease (PD) is defined as the appearance of endometrial cancer in patients. EAH after treatment will be defined as PR in patients with EC. Continuous therapies will be needed in PR, NR or PD.

After completion of study treatment, 3 months of maintenance treatment will be recommended for patients with CR, and they will be followed up for 2 years.

In addition, we've already had a pilot study in 19 patients primarily diagnosed of endometrial atypical hyperplasia from August 2012 to April 2013. 10 patients were in Arm I and 9 patients were in Arm II. Metabolic syndrome were evaluated among all subjects. After treatment, megestrol acetate plus metformin worked better than megestrol acetate alone. But two arms showed no difference in NR patients, which may suggest metformin just worked as an antitumor drug more than an insulin sensitizer. More supportive researches are needed to verify it.

Study Type

Interventional

Enrollment (Actual)

150

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Fudan University Shanghai Cancer Center
      • Shanghai, Shanghai, China, 200011
        • Obstetrics and Gynecology Hospital, Fudan University
      • Shanghai, Shanghai, China
        • Shanghai Changning Maternity & Infant Health Hospital
      • Shanghai, Shanghai, China
        • Shanghai Sixth People's Hospital
    • Zhejiang
      • Hangzhou, Zhejiang, China
        • Zhejiang Cancer Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Be between the ages of 18-45 years old

  • Primarily have a confirmed diagnosis of endometrial atypical hyperplasia based upon D&C or hysteroscopy

    • OR primarily have a confirmed diagnosis of endometrial adenocarcinoma(G1, low tumor grade), based upon D&C or hysteroscopy, and three MRI parameters shows there's no myometrial invasion, extension beyond corpus, or enlarged lymph nodes
  • Have a desire for remaining reproductive function or uterus
  • Need to be able to undergo correlative treatment and follow-up

Exclusion Criteria:

  • Have a history of serious liver or renal dysfunction
  • Have a confirmed diagnosis of malignant tumor in genital system
  • Have taken oral contraceptive or other medicine for the treatment of endometrial hyperplasia in the past 6 months
  • Ask for removal of the uterus or other conservative treatment
  • serum CA-125 > 35 Um/L

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Megestrol acetate and metformin
Patients will receive metformin 500 mg by mouth third daily and megestrol acetate 160 mg by mouth daily for 3 months.Then an hysteroscope will be used to evaluate the endometrial condition, and the findings will be recorded.
Drug: Megestrol acetate and metformin
Patients will receive metformin 500 mg by mouth third daily and megestrol acetate 160 mg by mouth daily for 3 months.
Other Names:
  • Megestrol acetate: Megace
  • Metformin: Fortamet, Glucophage
Experimental: Megestrol acetate
Patients will receive megestrol acetate 160 mg by mouth daily for 3 months.Then an hysteroscope will be used to evaluate the endometrial condition, and the findings will be recorded.
Drug: Megestrol acetate
Patients will receive megestrol acetate 160 mg by mouth daily for 3 months.
Other Names:
  • Megestrol acetate: Megace

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative CR Rates Within 16 Weeks
Time Frame: 16 weeks after initial treatment

The primary objective was to determine whether metformin plus MA would be associated with a higher CR rate at 3 months of treatment compared with MA alone. However, for patients who eventually underwent the first and second hysteroscopies for endometrium evaluation within 16 weeks of the treatment, the cumulative CR rates within 16 weeks (16w-CR) were analysed as first end point instead of the CR rate at 3 months.

Complete response was defined as the reversion of AEH/EEC to proliferative or secretory endometrium in pathology.
16 weeks after initial treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative CR Rates Within 32 Weeks
Time Frame: 32 weeks after initial treatment
One of the secondary objectives was between-group comparisons of the cumulative CR rate at 6 months treatment. However, for patients who eventually underwent the second hysteroscopies for endometrium evaluation within 32 weeks of the treatment, the cumulative CR rates within 32 weeks (32w-CR rates) were analysed as secondary end point instead of the CR rate at 6 months.
32 weeks after initial treatment
Recurrence Rate
Time Frame: through study completion, a median time of 33 months
All patients were followed up till February 2019. Statistics of patients who didn't accept hysterectomy and were not lost to follow up were analyzed.
through study completion, a median time of 33 months
Pregnancy Rate
Time Frame: through study completion, a median time of 33 months
All patients were followed up till February 2019. The pregnancy rate was calculated only in women who planned for parenthood immediately after achieving CR.
through study completion, a median time of 33 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xiaojun Chen

Collaborators

Zhejiang Cancer Hospital
Fudan University
Shanghai 6th People's Hospital
Shanghai Changning Maternity & Infant Health Hospital

Investigators

  • Study Chair: Xiaojun Chen, PhD, Obstetrics & Gynecology Hospital of Fudan University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2013

Primary Completion (Actual)

October 1, 2017

Study Completion (Actual)

October 1, 2017

Study Registration Dates

First Submitted

October 16, 2013

First Submitted That Met QC Criteria

October 20, 2013

First Posted (Estimate)

October 24, 2013

Study Record Updates

Last Update Posted (Actual)

September 14, 2021

Last Update Submitted That Met QC Criteria

September 10, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 134119a4500

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Endometrial Adenocarcinoma

Clinical Trials on Megestrol acetate and metformin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kuwait

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe