An Endometrial Cancer Chemoprevention Study of Metformin

Study Description

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Gynecology	Drug: Metformin; Other: Placebo; Procedure: Endometrial Biopsy; Behavioral: Lifestyle Intervention; Behavioral: Questionnaires	Phase 3

  Show Detailed Description

Study Design

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	100 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	An Endometrial Cancer Chemoprevention Study of Metformin Versus No Treatment in Women With a Body Mass Index (BMI) >/= 30 kg.m2 and Hyperinsulinemia
Actual Study Start Date :	May 2013
Estimated Primary Completion Date :	May 2019
Estimated Study Completion Date :	May 2019

Arms and Interventions

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: Metformin; Participants gradually increase the dose of metformin 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, participant continues to take 2 capsules of metformin 2 times each day. Each capsule is 425 mg.	Drug: Metformin; Participants gradually increase the dose of metformin 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, participant continues to take 2 capsules of metformin 2 times each day. Each capsule is 425 mg. Procedure: Endometrial Biopsy; Endometrial biopsies obtained at baseline and after 4 months. Behavioral: Questionnaires; Completion of questionnaires about diet and exercise at baseline, during treatment and at end of study. Questionnaires take about 30-40 minutes to complete.; Other Name: surveys
Experimental: Placebo + Lifestyle Intervention; Placebo taken by mouth twice daily for 4, 30 day cycles. Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.	Other: Placebo; Placebo taken by mouth twice daily for 4, 30 day cycles.; Other Name: sugar pill Procedure: Endometrial Biopsy; Endometrial biopsies obtained at baseline and after 4 months. Behavioral: Lifestyle Intervention; Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period. Behavioral: Questionnaires; Completion of questionnaires about diet and exercise at baseline, during treatment and at end of study. Questionnaires take about 30-40 minutes to complete.; Other Name: surveys
Experimental: Metformin + Lifestyle Intervention; Participants gradually increase the dose of metformin 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, participant continues to take 2 capsules of metformin 2 times each day. Each capsule is 425 mg. Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.	Drug: Metformin; Participants gradually increase the dose of metformin 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, participant continues to take 2 capsules of metformin 2 times each day. Each capsule is 425 mg. Procedure: Endometrial Biopsy; Endometrial biopsies obtained at baseline and after 4 months. Behavioral: Lifestyle Intervention; Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period. Behavioral: Questionnaires; Completion of questionnaires about diet and exercise at baseline, during treatment and at end of study. Questionnaires take about 30-40 minutes to complete.; Other Name: surveys
Placebo Comparator: Placebo; Placebo taken by mouth twice daily for 4, 30 day cycles.	Other: Placebo; Placebo taken by mouth twice daily for 4, 30 day cycles.; Other Name: sugar pill Procedure: Endometrial Biopsy; Endometrial biopsies obtained at baseline and after 4 months. Behavioral: Questionnaires; Completion of questionnaires about diet and exercise at baseline, during treatment and at end of study. Questionnaires take about 30-40 minutes to complete.; Other Name: surveys

Outcome Measures

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Effect of Metformin and/or Lifestyle Intervention on Biomarkers. [ Time Frame: 4 months ]
   Differences in Ki-67 and other biomarkers analyzed using a 2x2 ANOVA. Other biomarkers examined include a) a panel of genes relevant to estrogen dependent endometrial proliferation, hyperplasia and cancer using Q-PCR, b) biomarkers specific to the effect of metformin treatment (phospho-AMPKa, phospho-ACC, phospho-mTOR and phospho-S6 ribosomal protein and c) potential biomarkers of modulation of insulin sensitivity on the human endometrial proteome using reverse phase protein arrays (RPPA).

Eligibility Criteria

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	50 Years to 65 Years (Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

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).

Exclusion Criteria:

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

Contacts and Locations

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Karen H. Lu, MD	M.D. Anderson Cancer Center

More Information

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

University of Texas MD Anderson Cancer Center Website 

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT01697566 History of Changes
Other Study ID Numbers:	2011-0739; 5P50CA098258 ( U.S. NIH Grant/Contract ); NCI-2013-00834 ( Registry Identifier: NCI CTRP )
First Posted:	October 2, 2012
Last Update Posted:	May 11, 2018
Last Verified:	May 2018

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by M.D. Anderson Cancer Center:

Gynecology; Endometrial Cancer Chemoprevention; Obese; Body Mass Index (BMI) >/= 35 kg.m2; Post-menopausal; Hyperinsulinemia	Metformin; Placebo; Sugar pill; Lifestyle intervention; Diet; Exercise

Additional relevant MeSH terms:

Endometrial Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms	Uterine Diseases; Genital Diseases, Female; Metformin; Hypoglycemic Agents; Physiological Effects of Drugs