An Endometrial Cancer Chemoprevention Study of Metformin

This study is currently recruiting participants.
Verified December 2013 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
SPORE
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01697566
First received: September 28, 2012
Last updated: December 5, 2013
Last verified: December 2013
  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:


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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   50 Years to 65 Years
Genders 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 = 32 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
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:
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: December 5, 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
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Genital Diseases, Female
Glucose Metabolism Disorders
Metabolic Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014