Trial Outcomes & Findings for Megestrol Acetate Plus Metformin to Megestrol Acetate in Patients With Endometrial Atypical Hyperplasia or Early Stage Endometrial Adenocarcinoma (NCT NCT01968317)
NCT ID: NCT01968317
Last Updated: 2021-09-14
Results Overview
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.
COMPLETED
PHASE2
150 participants
16 weeks after initial treatment
2021-09-14
Participant Flow
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).
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.
Participant milestones
| Measure |
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.
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.
|
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.
Megestrol acetate: Patients will receive megestrol acetate 160 mg by mouth daily for 3 months.
|
|---|---|---|
|
Overall Study
STARTED
|
76
|
74
|
|
Overall Study
COMPLETED
|
76
|
74
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Megestrol Acetate Plus Metformin to Megestrol Acetate in Patients With Endometrial Atypical Hyperplasia or Early Stage Endometrial Adenocarcinoma
Baseline characteristics by cohort
| Measure |
Megestrol Acetate and Metformin
n=76 Participants
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.
|
Megestrol Acetate
n=74 Participants
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
n=150 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
32.0 years
STANDARD_DEVIATION 4.5 • n=5 Participants
|
33.4 years
STANDARD_DEVIATION 5.2 • n=7 Participants
|
32.6 years
STANDARD_DEVIATION 4.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
76 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
150 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
76 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
150 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
China
|
76 participants
n=5 Participants
|
74 participants
n=7 Participants
|
150 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 16 weeks after initial treatmentPopulation: 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.
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.
Outcome measures
| Measure |
Megestrol Acetate and Metformin
n=67 Participants
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.
|
Megestrol Acetate
n=58 Participants
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.
|
|---|---|---|
|
Cumulative CR Rates Within 16 Weeks
|
23 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: 32 weeks after initial treatmentPopulation: 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.
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.
Outcome measures
| Measure |
Megestrol Acetate and Metformin
n=70 Participants
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.
|
Megestrol Acetate
n=66 Participants
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.
|
|---|---|---|
|
Cumulative CR Rates Within 32 Weeks
|
52 Participants
|
45 Participants
|
SECONDARY outcome
Timeframe: through study completion, a median time of 33 monthsPopulation: 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.
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.
Outcome measures
| Measure |
Megestrol Acetate and Metformin
n=69 Participants
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.
|
Megestrol Acetate
n=66 Participants
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.
|
|---|---|---|
|
Recurrence Rate
|
7 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: through study completion, a median time of 33 monthsPopulation: In MA+metformin group only 31 cases wanted to have a baby, and that in MA group were 37.
All patients were followed up till February 2019. The pregnancy rate was calculated only in women who planned for parenthood immediately after achieving CR.
Outcome measures
| Measure |
Megestrol Acetate and Metformin
n=37 Participants
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.
|
Megestrol Acetate
n=31 Participants
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.
|
|---|---|---|
|
Pregnancy Rate
|
19 Participants
|
15 Participants
|
Adverse Events
Megestrol Acetate and Metformin
Megestrol Acetate
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Megestrol Acetate and Metformin
n=76 participants at risk
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.
|
Megestrol Acetate
n=74 participants at risk
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.
|
|---|---|---|
|
Endocrine disorders
Weight gain
|
38.2%
29/76 • Number of events 29 • 32 weeks
|
45.9%
34/74 • Number of events 34 • 32 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
15.8%
12/76 • Number of events 12 • 32 weeks
|
4.1%
3/74 • Number of events 3 • 32 weeks
|
|
Renal and urinary disorders
Increased nocturnal urine
|
19.7%
15/76 • Number of events 15 • 32 weeks
|
27.0%
20/74 • Number of events 20 • 32 weeks
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
13.2%
10/76 • Number of events 10 • 32 weeks
|
13.5%
10/74 • Number of events 10 • 32 weeks
|
|
Vascular disorders
Breast pain OR Abdominal pain
|
22.4%
17/76 • Number of events 17 • 32 weeks
|
27.0%
20/74 • Number of events 20 • 32 weeks
|
|
Gastrointestinal disorders
Nausea
|
10.5%
8/76 • Number of events 8 • 32 weeks
|
5.4%
4/74 • Number of events 4 • 32 weeks
|
|
Congenital, familial and genetic disorders
Uterine hemorrhage
|
7.9%
6/76 • Number of events 6 • 32 weeks
|
17.6%
13/74 • Number of events 13 • 32 weeks
|
|
Nervous system disorders
Dizziness
|
9.2%
7/76 • Number of events 7 • 32 weeks
|
9.5%
7/74 • Number of events 7 • 32 weeks
|
|
Gastrointestinal disorders
Constipation
|
1.3%
1/76 • Number of events 1 • 32 weeks
|
1.4%
1/74 • Number of events 1 • 32 weeks
|
|
General disorders
Insomnia
|
2.6%
2/76 • Number of events 2 • 32 weeks
|
4.1%
3/74 • Number of events 3 • 32 weeks
|
|
Skin and subcutaneous tissue disorders
Allergic reaction
|
10.5%
8/76 • Number of events 8 • 32 weeks
|
6.8%
5/74 • Number of events 5 • 32 weeks
|
|
General disorders
Anorexia
|
6.6%
5/76 • Number of events 5 • 32 weeks
|
0.00%
0/74 • 32 weeks
|
Additional Information
Xiaojun Chen
Obstetrics and Gynecology Hospital of Fudan University
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60