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
Condition: Adenocarcinoma of the Endometrium
MeSH terms: Adenocarcinoma; Uterine Neoplasms
Intervention: Metformin
Intervention MeSH terms: Metformin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: Female
Minimum age: 45 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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.