Longitudinal Follow-up in Women With Endometrial Hyperplasia Without Atypia

Study Overview
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Brief Summary
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This study will prospectively enroll a total of 1000 patients (200 per year) simple hyperplasia/complex hyperplasia (SH/CH) without atypia. All subjects will receive education for exercise and weight control and be randomized 1:1 to with or without metformin intervention. At the end of this 3-year project, an interim analysis will be performed. Since long-term follow-up is intended, therefore for the 4th to 6th year a new grant support will be looked for. The long-term occurrence of endometrial cancer (up to15 years) data will be acquired from national cancer registry, which permission is addressed in the informed sent.

Detailed Description
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The first year: (1) the cumulative progression rate of SH/CH without atypia to endometrial cancer (EC) of the 1989-2011 cohort will be investigated by linking with national health databases from Health and Welfare Data Science Center (HWDC); (2) Prospectively enroll 200 patients with SH/CH without atypia and deliver education for exercise and weight control and collect the related biospecimens and data; (3) 1:1 randomized to with or without metformin intervention. The 2nd year: (1) analyze the whole genome sequencing (WGS) data of those progressed and non-progressed ; (2) analyze the metabolomic data in relation to exercise and weight control data. The 3rd year: (1) validate microRNA (miR) panel in tissues and sera selected by CMRPG3G1511-3; (2) analyze data of MiR panel, degree of exercise/weight control, clinical lab data, and demographic data on EC progression rate; (3) Incremental predicting proficiency of the model including metabolomics data and WGS.

Official Title
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MicroRNAs as Biomarkers of Predicting Future Endometrial Malignancy and Longitudinal Follow-up With Randomized Intervention in Women With Endometrial Hyperplasia Without Atypia

Conditions
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Female

Intervention / Treatment
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* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged ≧ 20 years Histological diagnosis of SH/CH without atypia Not taking Metformin for diabetes mellitus currently Adequate kidney function Provided informed consent within 3 months of diagnosis No previous history of breast cancer with tamoxifen use Willing to be followed for 5 years Exclusion Criteria: Atypical hyperplasia or EC found within 3 months after enrollment History or concurrent gynecologic cancers or cervical intraepithelial neoplasia Pregnancy test positive History of intolerance to Metformin Family history of HNPCC

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: metformin group<br>During the intervention period, metformin is given 500 mg tablet b.i.d. We will deliver education for exercise and weight control to all eligible participants | Drug: Metformin<br>* During the intervention period, metformin is given 500 mg tablet b.i.d. Those who stopped taking metformin will remain in the study not counting as protocol violation.<br>* Other names: Uformin Tablet 500mg;|
| No Intervention: Observation group<br>only exercise and weight control to all eligible participants | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The area under the receiver operating characteristic curve (ROC curve) (AUC) of the prediction miR panel of the 3 miRs. | The primary endpoint of the randomized prospective study is to evaluate the ROC of the prediction miR panel of the 3 miRs. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression among groups | Incidence of progression to endometrial cancer among groups, Proportion of participants with treatment-related adverse events as assessed by CTCAE v4.0 | 3 years | 
| Subgroup analysis in body-weight control | Follow up the body-weight control | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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simple hyperplasia, Metformain