An Endometrial Cancer Chemoprevention Study of Metformin
Basic Trial Information
The goal of this clinical research study is to learn about the effects of metformin and/or a program called "lifestyle intervention" on the endometrium (inner lining of the uterus) in post-menopausal women who are also obese (both are risk factors for endometrial cancer). Researchers also want to learn how insulin levels will be affected by metformin, diet and/or exercise.
Metformin is designed to treat both diabetes and insulin resistance. Insulin resistance is a condition in which the body makes insulin but does not use it properly. It is often referred to as "pre-diabetes". Many people with insulin resistance have high levels of both sugar and insulin in their blood at the same time, which have been reported in patients with endometrial cancer.
In this study, metformin will be compared to a placebo. A placebo is not a drug. It looks like the study drug but is not designed to treat any disease or illness. It is designed to be compared with a study drug to learn if the study drug has any real effect.
Lifestyle intervention is made up of a series of in-person sessions where you meet with a coach to discuss strategies for losing weight and ways to increase physical activity. It also consists of materials designed to help you lose weight and will offer opportunities for supervised exercise.
Further Study Information
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:
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:
After week 4, you will continue to take 2 capsules of metformin/placebo 2 times each day.
If you are receiving the 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.
Before you can begin receiving the study drug/placebo:
At Month 1, all participants will return for a study visit. The following tests and procedures will be performed:
At each month, you will be asked about any symptom(s) that you may have to learn if it is related to the study. If you are called, this phone call should last about 5 minutes. If you are asked in a in-person visit, the visit can last up to an hour.
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.
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:
About 1 year after the screening visits (+/- 1 month), the following tests and procedures will be performed:
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.
1. For this study, only women will be enrolled.
2. Body Mass Index (BMI) > or = 30 kg/m2
3. Not frankly diabetic, as measured by a fasting blood glucose </=126 mg/dL.
4. Demonstrate hyperinsulinemia with a QUICK I value </= 0.357.
5. Age >/= 50 and </= 65
6. Zubrod Performance Scale 0-1
7. Hemoglobin >/= 10 g/dl
8. TSH 0.27 - 4.20 µlU/mL
9. Menopause as defined as no menses for 1 year and/or FSH >/= 25.8 mIU/ml
10. Must be able to read, write, and speak English.
11. Must have a Primary Care Provider (PCP).
1. Prior hysterectomy or endometrial ablation
2. ALT >/r = 2.0x Upper Limit of Normal (ULN)
3. Serum creatinine > /= 1.4 mg/dl
4. Triglycerides (fasting) >/ = 400
5. Known inability to participate in the ongoing appointments for the four months of the study and scheduled follow-up tests.
6. Significant medical or psychiatric history which would make the participant a poor protocol candidate, in the opinion of the principal investigator, for any aspect of study participation including metformin, unsupervised exercise program or dietary behavior change.
7. Participant reported history of congestive heart failure
8. Prior treatment with Metformin
9. Currently being treated for diabetes or meeting criteria for new diagnosis of diabetes.
10. Known allergy to Metformin or other biguanide (Proguanil).
11. Use of Aromatase Inhibitors, GNRH-agonists i.e.Lupron, Zoladex within the last 6 months
12. Use of SERMS (selective estrogen receptor modulators) in the past 6 months, including Tamoxifen and Raloxifene
13. Hormone replacement therapy within the last 6 months
14. Women who have been treated with chemotherapy for prior malignant disease or currently have an untreated malignancy other than non-melanoma skin cancer
15. Patients who have had prior radiation to the pelvis
Trial Contact Information
Trial Lead Organizations/Sponsors
M. D. Anderson Cancer Center at University of Texas
Karen H. Lu, Principal Investigator
Karen H. Lu, MD
Link to the current ClinicalTrials.gov record.
Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.