A Randomized Pilot Study to Evaluate the Effects of a Short Course of Metformin Versus No Therapy in the Period Prior to Hysterectomy for Grade 1-2 Adenocarcinoma of the Endometrium in Obese Non-Diabetic Women

Study Overview
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Brief Summary
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The purpose of this research is to determine the effects of Metformin, a well tolerated drug widely prescribed for treatment of Type 2 Diabetes Mellitus, on endometrium cancer patients.

Official Title
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A Randomized Pilot Study to Evaluate the Effects of a Short Course of Metformin Versus No Therapy in the Period Prior to Hysterectomy for Grade 1-2 Adenocarcinoma of the Endometrium in Obese Non-Diabetic Women

Conditions
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Adenocarcinoma of the Endometrium

Intervention / Treatment
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* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological confirmed diagnosis of grade I or II adenocarcinoma of the endometrium Must be obese as defined by a body mass index (BMI) greater than or equal to 30 kg/m2 Candidate for surgical removal of their uterus as part of their endometrial cancer treatment Subjects must have signed informed consent Age 42 - 65 years of age Electrocorticogram (ECOG) Performance status of 0 - 2 History of adequate renal, liver, and bone marrow function: Hb: (adequate for surgical intervention, with transfusion if necessary) White Blood Cell (WBC): (normal range) Platelets: (180K/cmm) Liver Function Test(LFTs): Normal bilirubin (<2.0mg/dL), AST/ALT (2xULN) Renal function: creatinine less than 1.4 Female subjects must either not be of child-bearing potential or must have a negative urine pregnancy test within 7 days of randomization to Metformin. Subjects are considered not of child-bearing potential if they are surgically sterile or they are postmenopausal for greater than 12 months. Exclusion Criteria: Poorly differentiated cancer or any of the high-risk subtypes of endometrial cancer including serous, clear cell, or carcinosarcoma History of diabetes mellitus Type 1 or Type 2. Receiving metformin prior to enrollment Known hypersensitivity to metformin. Unable to swallow and retain oral medication. Pregnant or lactating. Previous or concurrent malignancies, except non-melanoma skin cancers, unless curatively treated and with no evidence of recurrence for > 5 years If the physician feels that the candidate is not suitable for the study, he/she will be excluded. Currently taking biguanides, sulfonylurea drugs, thiazolidinediones, insulin, or mTOR or DPP-4 inhibitors or having taken any of these medications during the 12 weeks prior to study participation. Clinical symptoms of gastrointestinal obstruction or bleeding and consideration for immediate surgery or immediate neoadjuvant chemoradiation. History of lactic or other metabolic acidosis. Uncontrolled infectious disease. History of positivity for human immunodeficiency virus (HIV). History of congestive heart failure requiring pharmacologic treatment. History of excessive alcohol abuse, defined by a habitual intake of more than three drinks daily. Mal-absorption syndrome, disease affecting gastrointestinal function, or previous resection of the stomach or small bowel. Current use of medications for weight loss. Currently taking cimetidine, thiazide diuretics or cephalexin. If a patient needs some of these agents, alternative agents should be substituted.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 - Metformin<br>oral metformin at 500 mg twice a day for 14-21 days followed by surgery | Drug: Metformin<br> <br> |
| No Intervention: Group 2 - No treatment<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IHC-based Tissue Markers of Proliferation |  | 1 year |