Megestrol Acetate Plus Metformin to Megestrol Acetate in Patients With Endometrial Atypical Hyperplasia or Early Stage Endometrial Adenocarcinoma
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
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 Design
Arms and Interventions
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:
|
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:
|
Outcome Measures
Primary Outcome Measures
- Cumulative CR Rates Within 16 Weeks [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.
Secondary Outcome Measures
- Cumulative CR Rates Within 32 Weeks [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.
- Recurrence Rate [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.
- Pregnancy Rate [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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Obstetrics and Gynecology Hospital, Fudan University | Shanghai | Shanghai | China | 200011 |
2 | Fudan University Shanghai Cancer Center | Shanghai | Shanghai | China | 200032 |
3 | Shanghai Changning Maternity & Infant Health Hospital | Shanghai | Shanghai | China | |
4 | Shanghai Sixth People's Hospital | Shanghai | Shanghai | China | |
5 | Zhejiang Cancer Hospital | Hangzhou | Zhejiang | China |
Sponsors and Collaborators
- Xiaojun Chen
- Fudan University
- Shanghai 6th People's Hospital
- Zhejiang Cancer Hospital
- Shanghai Changning Maternity & Infant Health Hospital
Investigators
- Study Chair: Xiaojun Chen, PhD, Obstetrics & Gynecology Hospital of Fudan University
Study Documents (Full-Text)
More Information
Publications
None provided.- 134119a4500
Study Results
Participant Flow
Recruitment Details | 307 patients from Obstetrics and Gynaecology Hospital of Fudan University (Shanghai, China) were enrolled to this study between October 2013 to October 2017, including 237 patients with atypical endometrial hyperplasia (AEH) and 70 patients with well-differentiated endometrioid endometrial cancer (EEC). |
---|---|
Pre-assignment Detail | 157 of 307 enrolled patients were deemed ineligible, including 28 patients with hysterectomy history, 31 patients with AEH/EEC history, 67 patients with progestin use history, 10 patients refusing to attend this trial, 21 patients transferred to other hospital were excluded from this trial. |
Arm/Group Title | Megestrol Acetate and Metformin | Megestrol Acetate |
---|---|---|
Arm/Group Description | 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. 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. | 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. Megestrol acetate: Patients will receive megestrol acetate 160 mg by mouth daily for 3 months. |
Period Title: Overall Study | ||
STARTED | 76 | 74 |
COMPLETED | 76 | 74 |
NOT COMPLETED | 0 | 0 |
Baseline Characteristics
Arm/Group Title | Megestrol Acetate and Metformin | Megestrol Acetate | Total |
---|---|---|---|
Arm/Group Description | 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. 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. | 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. Megestrol acetate: Patients will receive megestrol acetate 160 mg by mouth daily for 3 months. | Total of all reporting groups |
Overall Participants | 76 | 74 | 150 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
32.0
(4.5)
|
33.4
(5.2)
|
32.6
(4.9)
|
Sex: Female, Male (Count of Participants) | |||
Female |
76
100%
|
74
100%
|
150
100%
|
Male |
0
0%
|
0
0%
|
0
0%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
Asian |
76
100%
|
74
100%
|
150
100%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
Black or African American |
0
0%
|
0
0%
|
0
0%
|
White |
0
0%
|
0
0%
|
0
0%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Region of Enrollment (participants) [Number] | |||
China |
76
100%
|
74
100%
|
150
100%
|
Outcome Measures
Title | Cumulative CR Rates Within 16 Weeks |
---|---|
Description | 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. |
Time Frame | 16 weeks after initial treatment |
Outcome Measure Data
Analysis Population Description |
---|
In MA+metformin group, 9 cases were excluded in primary analysis for 1 asking for surgery and 8 missing hysteroscopic evaluation. In MA group, 16 cases were excluded for 1 asking for surgery and 15 missing hysteroscopic evaluation. |
Arm/Group Title | Megestrol Acetate and Metformin | Megestrol Acetate |
---|---|---|
Arm/Group Description | Patients will receive metformin 500 mg by mouth three times daily and megestrol acetate 160 mg by mouth daily. Hysteroscopic evaluation was performed every 3 months during the therapy to evaluate the endometrial condition, and the findings will be recorded. | Patients will receive megestrol acetate 160 mg by mouth daily. Hysteroscopic evaluation was performed every 3 months during the therapy to evaluate the endometrial condition, and the findings will be recorded. |
Measure Participants | 67 | 58 |
Count of Participants [Participants] |
23
30.3%
|
12
16.2%
|
Title | Cumulative CR Rates Within 32 Weeks |
---|---|
Description | 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. |
Time Frame | 32 weeks after initial treatment |
Outcome Measure Data
Analysis Population Description |
---|
In MA+metformin group, 6 cases were excluded in this analysis for 3 asking for surgery and 3 missing hysteroscopic evaluation. In MA group, 8 cases were excluded for 2 asking for surgery and 6 missing hysteroscopic evaluation. |
Arm/Group Title | Megestrol Acetate and Metformin | Megestrol Acetate |
---|---|---|
Arm/Group Description | Patients will receive metformin 500 mg by mouth three times daily and megestrol acetate 160 mg by mouth daily. Hysteroscopic evaluation was performed every 3 months during the therapy to evaluate the endometrial condition, and the findings will be recorded. | Patients will receive megestrol acetate 160 mg by mouth daily. Hysteroscopic evaluation was performed every 3 months during the therapy to evaluate the endometrial condition, and the findings will be recorded. |
Measure Participants | 70 | 66 |
Count of Participants [Participants] |
52
68.4%
|
45
60.8%
|
Title | Recurrence Rate |
---|---|
Description | 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. |
Time Frame | through study completion, a median time of 33 months |
Outcome Measure Data
Analysis Population Description |
---|
In MA+metformin group, 3 cases were excluded in this analysis for surgery, 3 for lost to follow-up, and 1 for still in treatment. In MA group, 2 cases were excluded for surgery and 6 for lost to follow-up. |
Arm/Group Title | Megestrol Acetate and Metformin | Megestrol Acetate |
---|---|---|
Arm/Group Description | Patients will receive metformin 500 mg by mouth three times daily and megestrol acetate 160 mg by mouth daily. Hysteroscopic evaluation was performed every 3 months during the therapy to evaluate the endometrial condition, and the findings will be recorded. | Patients will receive megestrol acetate 160 mg by mouth daily. Hysteroscopic evaluation was performed every 3 months during the therapy to evaluate the endometrial condition, and the findings will be recorded. |
Measure Participants | 69 | 66 |
Count of Participants [Participants] |
7
9.2%
|
6
8.1%
|
Title | Pregnancy Rate |
---|---|
Description | All patients were followed up till February 2019. The pregnancy rate was calculated only in women who planned for parenthood immediately after achieving CR. |
Time Frame | through study completion, a median time of 33 months |
Outcome Measure Data
Analysis Population Description |
---|
In MA+metformin group only 31 cases wanted to have a baby, and that in MA group were 37. |
Arm/Group Title | Megestrol Acetate and Metformin | Megestrol Acetate |
---|---|---|
Arm/Group Description | Patients will receive metformin 500 mg by mouth three times daily and megestrol acetate 160 mg by mouth daily. Hysteroscopic evaluation was performed every 3 months during the therapy to evaluate the endometrial condition, and the findings will be recorded. | Patients will receive megestrol acetate 160 mg by mouth daily. Hysteroscopic evaluation was performed every 3 months during the therapy to evaluate the endometrial condition, and the findings will be recorded. |
Measure Participants | 37 | 31 |
Count of Participants [Participants] |
19
25%
|
15
20.3%
|
Adverse Events
Time Frame | 32 weeks | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | Megestrol Acetate and Metformin | Megestrol Acetate | ||
Arm/Group Description | Patients will receive metformin 500 mg by mouth three times daily and megestrol acetate 160 mg by mouth daily. After initiating the treatment, hysteroscopic evaluation was performed every 3 months during the therapy to evaluate the endometrial condition, and the findings will be recorded. | Patients will receive megestrol acetate 160 mg by mouth daily for 3 months.After initiating the treatment, hysteroscopic evaluation was performed every 3 months during the therapy to evaluate the endometrial condition, and the findings will be recorded. | ||
All Cause Mortality |
||||
Megestrol Acetate and Metformin | Megestrol Acetate | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/76 (0%) | 0/74 (0%) | ||
Serious Adverse Events |
||||
Megestrol Acetate and Metformin | Megestrol Acetate | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/76 (0%) | 0/74 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Megestrol Acetate and Metformin | Megestrol Acetate | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 47/76 (61.8%) | 46/74 (62.2%) | ||
Congenital, familial and genetic disorders | ||||
Uterine hemorrhage | 6/76 (7.9%) | 6 | 13/74 (17.6%) | 13 |
Endocrine disorders | ||||
Weight gain | 29/76 (38.2%) | 29 | 34/74 (45.9%) | 34 |
Gastrointestinal disorders | ||||
Diarrhea | 12/76 (15.8%) | 12 | 3/74 (4.1%) | 3 |
Nausea | 8/76 (10.5%) | 8 | 4/74 (5.4%) | 4 |
Constipation | 1/76 (1.3%) | 1 | 1/74 (1.4%) | 1 |
General disorders | ||||
Insomnia | 2/76 (2.6%) | 2 | 3/74 (4.1%) | 3 |
Anorexia | 5/76 (6.6%) | 5 | 0/74 (0%) | 0 |
Nervous system disorders | ||||
Dizziness | 7/76 (9.2%) | 7 | 7/74 (9.5%) | 7 |
Renal and urinary disorders | ||||
Increased nocturnal urine | 15/76 (19.7%) | 15 | 20/74 (27%) | 20 |
Skin and subcutaneous tissue disorders | ||||
Hyperhidrosis | 10/76 (13.2%) | 10 | 10/74 (13.5%) | 10 |
Allergic reaction | 8/76 (10.5%) | 8 | 5/74 (6.8%) | 5 |
Vascular disorders | ||||
Breast pain OR Abdominal pain | 17/76 (22.4%) | 17 | 20/74 (27%) | 20 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Name/Title | Xiaojun Chen |
---|---|
Organization | Obstetrics and Gynecology Hospital of Fudan University |
Phone | 33189900 |
xiaojunchen2013@sina.com |
- 134119a4500