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| Name | Class |
|---|---|
| Fudan University | OTHER |
| Shanghai 6th People's Hospital | OTHER |
| Zhejiang Cancer Hospital | OTHER |
| Shanghai Changning Maternity & Infant Health Hospital |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Megestrol acetate and metformin | Experimental | 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 | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Megestrol acetate and metformin | Drug | Patients will receive metformin 500 mg by mouth third daily and megestrol acetate 160 mg by mouth daily for 3 months. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative CR Rates Within 16 Weeks | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative CR Rates Within 32 Weeks | 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. |
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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
Have a desire for remaining reproductive function or uterus
Need to be able to undergo correlative treatment and follow-up
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Xiaojun Chen, PhD | Obstetrics & Gynecology Hospital of Fudan University | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Obstetrics and Gynecology Hospital, Fudan University | Shanghai | Shanghai Municipality | 200011 | China | ||
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.
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).
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 17, 2020 |
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| OTHER |
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|
| Megestrol acetate | Drug | Patients will receive megestrol acetate 160 mg by mouth daily for 3 months. |
|
|
| 32 weeks after initial treatment |
| Recurrence Rate | 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 | 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 |
| Fudan University Shanghai Cancer Center |
| Shanghai |
| Shanghai Municipality |
| 200032 |
| China |
| Shanghai Changning Maternity & Infant Health Hospital | Shanghai | Shanghai Municipality | China |
| Shanghai Sixth People's Hospital | Shanghai | Shanghai Municipality | China |
| Zhejiang Cancer Hospital | Hangzhou | Zhejiang | China |
| FG001 | 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. |
| COMPLETED |
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| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cumulative CR Rates Within 16 Weeks | 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. | 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. | Posted | Count of Participants | Participants | 16 weeks after initial treatment |
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| Secondary | Cumulative CR Rates Within 32 Weeks | 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. | 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. | Posted | Count of Participants | Participants | 32 weeks after initial treatment |
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| Secondary | Recurrence Rate | 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. | 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. | Posted | Count of Participants | Participants | through study completion, a median time of 33 months |
|
| ||||||||||||||||||||||||||||||
| Secondary | Pregnancy Rate | All patients were followed up till February 2019. The pregnancy rate was calculated only in women who planned for parenthood immediately after achieving CR. | In MA+metformin group only 31 cases wanted to have a baby, and that in MA group were 37. | Posted | Count of Participants | Participants | through study completion, a median time of 33 months |
|
|
32 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Megestrol Acetate and Metformin | 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. | 0 | 76 | 0 | 76 | 47 | 76 |
| EG001 | Megestrol Acetate | 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. | 0 | 74 | 0 | 74 | 46 | 74 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Weight gain | Endocrine disorders | Non-systematic Assessment |
| ||
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Increased nocturnal urine | Renal and urinary disorders | Non-systematic Assessment |
| ||
| Hyperhidrosis | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| ||
| Breast pain OR Abdominal pain | Vascular disorders | Non-systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Uterine hemorrhage | Congenital, familial and genetic disorders | Non-systematic Assessment |
| ||
| Dizziness | Nervous system disorders | Non-systematic Assessment |
| ||
| Constipation | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Insomnia | General disorders | Non-systematic Assessment |
| ||
| Allergic reaction | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| ||
| Anorexia | General disorders | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Xiaojun Chen | Obstetrics and Gynecology Hospital of Fudan University | 33189900 | xiaojunchen2013@sina.com |
| Nov 26, 2020 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D004714 | Endometrial Hyperplasia |
| ID | Term |
|---|---|
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
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| ID | Term |
|---|---|
| D019290 | Megestrol Acetate |
| D008687 | Metformin |
| ID | Term |
|---|---|
| D008535 | Megestrol |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
|
| Unknown or Not Reported |
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| Units | Counts |
|---|
| Participants |
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