Trial record 13 of 19 for:    breast cancer AND premenopausal | Open Studies | United States

Phase II Study of Metformin for Reduction of Obesity-Associated Breast Cancer Risk

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by University of Arizona
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sherry Chow, University of Arizona
ClinicalTrials.gov Identifier:
NCT02028221
First received: January 2, 2014
Last updated: February 11, 2014
Last verified: February 2014
  Purpose

Overweight and obesity are well established risk factors for breast cancer that develop after menopause. The increased postmenopausal breast cancer risk in women who are overweight or obese is likely to be attributed to multiple metabolic disturbances. Metformin is a commonly used medication in diabetics to stabilize blood sugar. Association studies and laboratory studies have shown its potential to reduce the risk for development of cancer, including breast cancer. Recent pilot clinical studies in breast cancer patients suggest that metformin may only be effective in overweight or obese women with metabolic disturbances. We propose to conduct a clinical study of metformin in overweight or obese premenopausal women with metabolic disturbances. Study participants will be randomly assigned to receive metformin or placebo for 12 months. The study will evaluate whether metformin can result in favorable changes in risk features that have been associated with increased breast cancer risk. The risk features that will be examined in our study include breast density, certain proteins and hormones, products of body metabolism, and body weight and composition. The study should help determine the potential breast cancer preventive activity of metformin in a growing population at risk for multiple diseases.


Condition Intervention Phase
Breast Cancer Prevention
Drug: Metformin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Phase II Study of Metformin for Reduction of Obesity-Associated Breast Cancer Risk

Resource links provided by NLM:


Further study details as provided by University of Arizona:

Primary Outcome Measures:
  • change from baseline in breast density at 6 and 12 months [ Time Frame: baseline, 6 months, 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • change from baseline in serum insulin levels at 6 and 12 months [ Time Frame: baseline, 6 months, 12 months ] [ Designated as safety issue: No ]
  • change from baseline in serum IGF-1 to IGFBP-3 ratio at 6 and 12 months [ Time Frame: baseline, 6 months, 12 months ] [ Designated as safety issue: No ]
  • change from baseline in serum testosterone levels at 6 and 12 months [ Time Frame: baseline, 6 months, 12 months ] [ Designated as safety issue: No ]
  • change from baseline in serum leptin to adiponectin ratio at 6 and 12 months [ Time Frame: baseline, 6 months, 12 months ] [ Designated as safety issue: No ]
  • change from baseline in body weight at 6 and 12 months [ Time Frame: baseline, 6 months, 12 months ] [ Designated as safety issue: No ]
  • change from baseline in waist circumference at 6 and 12 months [ Time Frame: baseline, 6 months, 12 months ] [ Designated as safety issue: No ]
  • change from baseline in serum IGF-2 levels at 6 and 12 months [ Time Frame: baseline, 6 months, 12 months ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • change from baseline in plasma metabolomics profile at 6 and 12 months [ Time Frame: baseline, 6 months, 12 months ] [ Designated as safety issue: No ]
  • change from baseline in metabolomics profile in nipple aspirate fluid at 6 and 12 months [ Time Frame: baseline, 6 months, 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: January 2014
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
1 tablet daily by mouth X 4 weeks, then 1 tablet twice daily by mouth for the remaining duration of the trial (12 months)
Drug: Placebo
1 tablet daily by mouth X 4 weeks, then 1 tablet twice daily by mouth for the remaining duration of the trial (12 months)
Experimental: Metformin
metformin 850 mg 1 tablet taken by mouth daily X 4 weeks, then metformin 850 mg 1 tablet taken twice daily for the remaining duration of he intervention period.
Drug: Metformin
metformin 850 mg 1 tablet taken by mouth daily X 4 weeks, then metformin 850 mg 1 tablet taken twice daily for the duration of he intervention period.
Other Names:
  • Glucophage
  • Glumetza
  • Fortamet

Detailed Description:

High adiposity is a major risk factor for a number of chronic diseases, including type 2 diabetes, cardiovascular diseases, and certain types of cancer, including postmenopausal breast cancer. The increased postmenopausal breast cancer risk in women with high adiposity is likely to be attributed to multiple metabolic disturbances including altered circulating sex steroid hormones, hyperinsulinemic insulin resistance, altered expression and secretion of adipokines from adipose tissue, increased production of pro-inflammatory cytokines, and increased oxidative stress.

Metformin, a widely used antidiabetic drug, exerts favorable effects on multiple metabolic disturbances which may lead to reduction of breast cancer risk in women with high adiposity. In addition, metformin may exert a direct effect in mammary tissue through the activation of the AMP-activated protein kinase signaling pathway, leading to an antiproliferative effect and induction of apoptosis. Recent case control and cohort studies found that treatment with metformin appears to substantially reduce the risk for development of cancer in diabetics, including breast cancer. There are a number of ongoing clinical trials of metformin in breast cancer patients. However, applicability of these trials to at risk healthy women requires further research and the concurrent or prior cancer treatments in these trials hinder the evaluation of metformin as a single agent for breast cancer risk reduction. In addition, recent clinical and animal studies suggest that metformin may only exert tumor suppressive effects in metabolic phenotypes of high adiposity and metabolic disturbances.

We propose to conduct a Phase II randomized, double-blind, placebo-controlled trial of metformin in overweight/obese premenopausal women who have metabolic syndrome. This study population is at increased risk for postmenopausal breast cancer and has a high prevalence of metabolic disturbances. The overall objective of this study is to determine its potential effects on reduction of obesity-associated breast cancer risk.

  Eligibility

Ages Eligible for Study:   30 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Premenopausal women with regular menstrual cycles for the past 6 months preceding the time of registration
  • 30-45 years of age
  • Have a BMI of 25 kg/m2 or greater
  • Have metabolic syndrome defined as having any 3 of the following 5 criteria based on the statement from the American Heart Association and the National Heart, Lung, and Blood Institute (103):

    • Elevated waist circumference ≥ 88 cm (≥35 inches)
    • Elevated triglycerides (≥ 150 mg/dL (1.7 mmol/L) or on drug treatment for elevated triglycerides
    • Reduced HDL-C (< 50 mg/dL (1.3 mmol/L) or on drug treatment for reduced HDL-C
    • Elevated blood pressure (≥ 130 Hg systolic blood pressure or ≥85 mm Hg diastolic blood pressure or on antihypertensive drug treatment in a patient with a history of hypertension
    • Elevated fasting glucose (≥100 mg/dL)
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Postmenopausal women

    • Amenorrhea for at least 12 months (preceding the time of registration), or
    • History of hysterectomy and bilateral salpingo-oophorectomy, or
    • At least 55 years of age with prior hysterectomy with or without oophorectomy, or
    • Age 35 to 54 with a prior hysterectomy without oophorectomy OR with a status of ovaries unknown with documented follicle-stimulating hormone level demonstrating elevation in postmenopausal range
  • Women who are pregnant, planning pregnancy within the next year, or breastfeeding
  • On treatment with any drug for diabetes
  • Have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or any illness that would limit compliance with study requirements
  • Have received chemotherapy and/or radiation for any malignancy (excluding non-melanoma skin cancer and cancers confined to organs with removal as only treatment) in the past 5 years (preceding the time of registration)
  • Have received other investigational agents within the past 3 months (preceding the time of registration)
  • Have a history of lactic acidosis or risk factors for lactic acidosis
  • Have significant renal disease or dysfunction (creatinine ≥ 2 x ULN)
  • Have significant hepatic dysfunction (bilirubin ≥ 2 x ULN unless with Gilberts syndrome or AST/ALT ≥ 5 x ULN)
  • Have a history of alcoholism or high alcohol consumption (average of > 3 standard drinks/day)
  • Have a history of allergic reactions to metformin or similar drugs
  • Have a history of severe claustrophobia
  • Have electrically, magnetically, or mechanically activated implants including cardiac pacemaker, cochlear implants, magnetic surgical clips or prostheses
  • Have breast implants
  • Plan to undergo radiologic studies involving intravascular administration of iodinated contrast materials
  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: NCT02028221

Contacts
Contact: Frances Epstein 520-321-7798 fminter@email.arizona.edu
Contact: Valerie Butler 520-318-9298 vbutler@email.arizona.edu

Locations
United States, Arizona
University of Arizona Recruiting
Tucson, Arizona, United States, 85719
Sponsors and Collaborators
University of Arizona
Investigators
Principal Investigator: Sherry Chow, PhD University of Arizona
  More Information

No publications provided

Responsible Party: Sherry Chow, H-H. Sherry Chow, Ph.D., University of Arizona
ClinicalTrials.gov Identifier: NCT02028221     History of Changes
Other Study ID Numbers: 1300000596, 1R01CA172444-01A1
Study First Received: January 2, 2014
Last Updated: February 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Arizona:
Breast cancer prevention
metformin
Breast cancer risk reduction

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014