Evaluation of the Molecular Effects of Metformin on the Endometrium in Patients With Endometrial Cancer

The Study Drug:

Metformin is designed to treat both diabetes and insulin resistance. Both diabetes and
insulin resistance have been linked to endometrial cancer. Although you do not have a
diagnosis of diabetes, metformin may still have an affect on your cancer cells.

Study Visit (before taking Metformin):

If you are found eligible to take part in this study, you will have a study visit before you
begin taking Metformin. The following tests and procedures will be performed:

- Blood (about 2 tablespoons) and urine will be collected for research to look at
different hormone levels.

- If needed, a fasting glucose level will be obtained.

- If you are found not to be eligible your blood, urine, and tissue for research will be
discarded.

Study Drug Administration:

You will take metformin, by mouth, 1 time each morning, with breakfast, for at least 7 days
and up to 30 days until your scheduled surgery is performed. You will record the dates and
times you take metformin on a study drug calendar provided by the study staff. You will not
take metformin on the day of your surgery.

Study Tests (on the day of your surgery):

You will bring your study drug calendar to the clinic on the day of your surgery. The
following tests and procedures will also be performed:

- Blood (about 2 tablespoons) and urine will be collected for routine tests and to check
different hormone levels.

- During surgery, you will have a second endometrial biopsy for biomarker testing.

Length of Study:

You will be off study after your surgical procedure.

This is an investigational study.

Up to 30 women will take part in this study. Up to 25 participants will take part at MD
Anderson.

Inclusion Criteria:

1. Patients must have signed informed consent

2. Patients must have histologically-confirmed endometrial adenocarcinoma, any grade (1,
2, or 3) or a mixed tumor with at least an endometrioid component

3. Patients must be a candidate for surgical staging procedure

4. Patients must either be not of child bearing potential or have a negative pregnancy
test within 7 days of treatment. Patients are considered not of child bearing
potential if they are surgically sterile or they are postmenopausal for greater than
12 months

5. Patients must have a documented non-fasting plasma glucose level of less than or
equal to 125 mg/dL. If non-fasting plasma glucose is greater than125 mg/dL, patients
must have a fasting plasma glucose level less than or equal to 125 mg/dL

6. Patients must have an adequated renal function of >60cc/min as documented by the
Cockcroft Gualt creatinine clearance formula: (140 - age) x (weight Kg) DIVIDED BY
Estimated GFR+ 72x serum Creatinine (non-IDMS x 85 (female)

7. Patients must have adequate hepatic function as documented by a serum bilirubin < 2.5
mg/dL, regardless of whether patients have liver involvement secondary to tumor

Exclusion Criteria:

1. Patients with a known history of diabetes mellitus type 1 or 2 or currently taking
any hypoglycemic agents

2. Patients who have received metformin or another mTOR inhibitor in the last 2 years

3. Patients with uterine sarcomas

4. Patients who have received prior treatment for endometrial carcinoma with cytotoxic
or biologic chemotherapy. Patients who have only received hormonal therapy for
endometrial cancer may be included

5. Patients who have undergone definitive surgery including hysterectomy or endometrial
ablation

6. Patients who are not surgical candidates

7. Patients with a known hypersensitivity to metformin

8. Patients with metabolic acidosis, acute or chronic, including ketoacidosis or
increased risk of lactic acidosis

9. Patients who have a history of excessive alcohol use

10. Patients with a history of congestive heart failure requiring pharmacologic treatment

11. Patients with a known history of HIV

12. Patients older than 80 year of age