An Endometrial Cancer Chemoprevention Study of Metformin - Full Text View

Purpose

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	Intervention	Phase
Gynecology	Drug: Metformin Other: Placebo Procedure: Endometrial Biopsy Behavioral: Lifestyle Intervention Behavioral: Questionnaires	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	An Endometrial Cancer Chemoprevention Study of Metformin Versus No Treatment in Women With a Body Mass Index (BMI) >/= 35 kg.m2 and Hyperinsulinemia

Resource links provided by NLM:

MedlinePlus related topics: Benign Tumors Cancer Diabetes Medicines Exercise and Physical Fitness

Drug Information available for: Metformin Metformin hydrochloride

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

Effect of Metformin and/or Lifestyle Intervention on Biomarkers. [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
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).

Estimated Enrollment:	100
Study Start Date:	May 2013
Estimated Primary Completion Date:	May 2019 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Metformin 850 mg by mouth twice a day for four, 30 day cycles.	Drug: Metformin 850 mg by mouth twice a day for four, 30 day cycles. 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 Metformin 850 mg by mouth twice a day for four, 30 day cycles. Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.	Drug: Metformin 850 mg by mouth twice a day for four, 30 day cycles. 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

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Eligibility

Ages Eligible for Study:	50 Years to 60 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

For this study, only women will be enrolled.
Body Mass Index (BMI) > or = 35 kg/m2
Not frankly diabetic, as measured by a fasting blood glucose </=126 mg/dL.
Demonstrate hyperinsulinemia with a QUICK I value below 0.357.
Age >/= 50 and </= 60
Zubrod Performance Scale 0-1
Hemoglobin >/= 10 g/dl
TSH 0.50 - 5.50mcU/ml
Menopause as defined as no menses for 1 year and FSH greater than 50mIU/ml
Must be able to read, write, and speak English.
Must have a Primary Care Provider (PCP).

Exclusion Criteria:

Prior hysterectomy
ALT >/r = 2.0x Upper Limit of Normal (ULN)
Serum creatinine > /= 1.4 mg/dl
Triglycerides (fasting) >/ = 400
Known inability to participate in the ongoing appointments for the four months of the study and scheduled follow-up tests.
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.
Participant reported history of congestive heart failure
Prior treatment with Metformin
Currently being treated for diabetes or meeting criteria for new diagnosis of diabetes.
Known allergy to Metformin or other biguanide (Proguanil).
Use of Aromatase Inhibitors, GNRH-agonists i.e.Lupron, Zoladex within the last 6 months
Use of SERMS (selective estrogen receptor modulators) in the past 6 months, including Tamoxifen and Raloxifene
Hormone replacement therapy within the last 6 months
Women who have been treated with chemotherapy for prior malignant disease or currently have an untreated malignancy other than non-melanoma skin cancer
Patients who have had prior radiation to the pelvis

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01697566

Contacts

Contact: Karen H. Lu, MD

713-745-8902

Locations

United States, Texas
UT MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

SPORE

Investigators

Principal Investigator:

Karen H. Lu, MD

UT MD Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center Website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT01697566 History of Changes
Other Study ID Numbers:	2011-0739
Study First Received:	September 28, 2012
Last Updated:	May 2, 2013
Health Authority:	United States: Food and Drug Administration

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
Hyperinsulinism
Adenoma
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases

Genital Diseases, Female
Glucose Metabolism Disorders
Metabolic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2013