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) >/= 30 kg.m2 and Hyperinsulinemia

Resource links provided by NLM:

MedlinePlus related topics: Cancer

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 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

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Eligibility


Ages Eligible for Study:	50 Years to 65 Years (Adult)
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 = 30 kg/m2
Not frankly diabetic, as measured by a fasting blood glucose </=126 mg/dL.
Demonstrate hyperinsulinemia with a QUICK I value </= 0.357.
Age >/= 50 and </= 65
Zubrod Performance Scale 0-1
Hemoglobin >/= 10 g/dl
TSH 0.27 - 4.20 µlU/mL
Menopause as defined as no menses for 1 year and/or FSH >/= 25.8 mIU/ml
Must be able to read, write, and speak English.
Must have a Primary Care Provider (PCP).

Exclusion Criteria:

Prior hysterectomy or endometrial ablation
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

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

Additional Information:

University of Texas MD Anderson Cancer Center Website This link exits the ClinicalTrials.gov site


Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT01697566 History of Changes
Other Study ID Numbers:	2011-0739 5P50CA098258 NCI-2013-00834
Study First Received:	September 28, 2012
Last Updated:	June 9, 2016
Health Authority:	United States: Food and Drug Administration United States: Federal Government

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

ClinicalTrials.gov processed this record on September 23, 2016