Trial Information

An Endometrial Cancer Chemoprevention Study of Metformin Versus No Treatment in Women With a Body Mass Index (BMI) >/= 35 kg.m2 and Hyperinsulinemia

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned
(as in the roll of dice) to 1 of 4 study groups:

- If you are in Group 1, you will receive metformin only.

- If you are in Group 2, you will receive a placebo and lifestyle intervention.

- If you are in Group 3, you will receive metformin and lifestyle intervention.

- If you are in Group 4, you will receive a placebo only.

Neither you nor the study staff will know if you are receiving metformin or placebo.
However, if needed for your safety, the study staff will be able to find out what you are
receiving.

In the first month you will gradually increase the dose of metformin/placebo by mouth as
listed below:

- Week 1: One capsule each day

- Week 2: One capsule 2 times each day

- Week 3: One capsule 3 times each day

- Week 4: Two capsules 2 times each day

After week 4, you will continue to take 2 capsules of metformin/placebo 2 times each day.

If you are in Group 2 or 3, you will also receive lifestyle intervention. You will have 16
lifestyle intervention sessions over 4 months. At each of these sessions, you will discuss
methods for managing your weight. You will receive print materials and worksheets,
measuring utensils, and a food scale. You will be instructed how to use each of these
materials and how often to use them during the study. You will also be provided with
opportunities for supervised exercise (such as group exercise class and group walks).

If you are traveling during a scheduled session, it can be performed over the telephone.
Each call should last about 30 minutes, during which you will discuss the same goals and
information that you would discuss in the in-person sessions.

Study Visits:

Before you can begin receiving the study drug/placebo:

- You will have a dual energy x-ray absorptiometry (DEXA) scan to measure your body
composition. The scan requires you to lie still on a table for about 8-10 minutes
while a low-energy x-ray takes an image that allows the study staff to get an image of
your body fat density.

- You will be given an accelerometer (a small, portable device that measures your
physical activity) and be taught how to use it at the first Screening Visit. You will
wear the accelerometer at all times while you are awake for 7 days. At the second
Screening Visit, you will return the accelerometer at an intervention session. If you
are not able to return it at the second visit then you will mail it back to the study
staff in a pre-paid envelope. You will receive the accelerometer again at Month 4 and
wear it for another 7 days.

- You will receive a study diary in which you will record any and all exercise you
perform each day while you are on study. It should take about 5 minutes to complete
each time.

- You will complete questionnaires about diet and exercise. These questionnaires should
take about 30-40 minutes to complete.

- You will also be taught to complete a questionnaire on the internet to record the food
you eat in a 24 hour period. You will do this 3 times over a 2 week period. The first
time, you will complete it at the clinic. The study staff will call and remind you to
complete the questionnaire the other 2 times. Each time you complete this
questionnaire, it should take about 40 minutes.

At Month 1, all participants will return for a study visit. The following tests and
procedures will be performed:

- Blood (about 2 teaspoons) will be drawn for routine tests. If this blood draw shows
that your liver or kidney function is abnormal, you will need to return for an
additional blood draw at Month 2.

- You will have a physical exam, including measurement of your height, weight, and waist.

At each month, you will be called and asked about any side effects you may be having. This
phone call should last about 5 minutes. You may be asked about side effects in person if
you are already in the clinic.

Length of Study:

You will receive the study drug/placebo and/or lifestyle intervention for up to 4 months.
You will be taken off study if you have intolerable side effects or if you develop
endometrial cancer or hyperplasia during the study. Your participation in the study will be
over after the end-of-study visit.

Post-Treatment Visit:

At the end of the 4th month, you will have a post-treatment visit. You will repeat all
procedures performed in the first and second visit:

- Your height, weight, waist, and hip circumference will be measured.

- You will have a DEXA scan.

- You will complete the questionnaires about food, diet, and exercise.

- You will have an endometrial biopsy.

- Blood (about 8 tablespoons) will be drawn for routine tests and for biomarker testing.
You will have to fast (not eat or drink anything except water) for 12 hours before this
blood draw.

This is an investigational study. Metformin is FDA approved and commercially available for
the treatment of diabetes and insulin resistance.

Up to 100 patients will take part in this study. All will be enrolled at MD Anderson Cancer
Center.