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

NCT02028221 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 13000005961R01CA172444-01A1
• Study Type: interventional
• Target: 151
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer Prevention

Keywords

Breast cancer prevention; metformin; Breast cancer risk reduction

Outcome Measures

Primary Outcomes (2)

• Change in Breast Density at 6 Months

  change of dense breast volume at 6 months

  baseline, 6 months

• Change in Breast Density at 12 Months

  Change in dense breast volume at 12 months

  Baseline, 12 months

Secondary Outcomes (7)

• Change From Baseline in Serum Insulin Levels at 6 and 12 Months

  baseline, 6 months, 12 months

• Change From Baseline in Serum IGF-1 to IGFBP-3 Ratio at 6 and 12 Months

  baseline, 6 months, 12 months

• Change From Baseline in Serum Testosterone Levels at 6 and 12 Months

  baseline, 6 months, 12 months

• Change From Baseline in Serum Leptin to Adiponectin Ratio at 6 and 12 Months

  baseline, 6 months, 12 months

• Change From Baseline in Body Weight at 6 and 12 Months

  baseline, 6 months, 12 months

Other Outcomes (2)

• Change From Baseline in Plasma Metabolomics Profile at 6 and 12 Months

  baseline, 6 months, 12 months

• Change From Baseline in Metabolomics Profile in Nipple Aspirate Fluid at 6 and 12 Months

  baseline, 6 months, 12 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Metformin

EXPERIMENTAL

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

Interventions

Metformin DRUG

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.

Also known as: Glucophage, Glumetza, Fortamet

Metformin

Placebo DRUG

1 tablet daily by mouth X 4 weeks, then 1 tablet twice daily by mouth for the remaining duration of the trial (12 months)

Placebo

Eligibility Criteria

• Age: 21 Years - 54 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Premenopausal women
• years of age
• Have a BMI of 25 kg/m2 or greater
• No change in menstrual patterns for the past 6 months preceding the time of registration
• Waist circumference ≥ 35 inches or ≥ 31 inches for Asian Americans, individuals with polycystic ovary syndrome, or individuals with non-alcoholic fatty liver disease.
• Have at least one other component of metabolic syndrome (103) reported below:
• 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)
• Mammogram negative for breast cancer within the 12 months preceding the time of registration for women ≥ 50 years of age
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• 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 ≥ 1.4 mg/dL)
• Have significant hepatic dysfunction (bilirubin ≥ 1.5 x ULN unless with Gilberts syndrome or AST/ALT ≥ 3 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

Sponsors & Collaborators

• University of Arizona: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Arizona

Tucson, Arizona, 85719, United States

Location

Related Publications (2)

• Tapia E, Villa-Guillen DE, Chalasani P, Centuori S, Roe DJ, Guillen-Rodriguez J, Huang C, Galons JP, Thomson CA, Altbach M, Trujillo J, Pinto L, Martinez JA, Algotar AM, Chow HS. A randomized controlled trial of metformin in women with components of metabolic syndrome: intervention feasibility and effects on adiposity and breast density. Breast Cancer Res Treat. 2021 Nov;190(1):69-78. doi: 10.1007/s10549-021-06355-9. Epub 2021 Aug 12.

  PMID: 34383179 DERIVED

• Martinez JA, Chalasani P, Thomson CA, Roe D, Altbach M, Galons JP, Stopeck A, Thompson PA, Villa-Guillen DE, Chow HH. Phase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocol. BMC Cancer. 2016 Jul 19;16:500. doi: 10.1186/s12885-016-2551-3.

  PMID: 27430256 DERIVED

MeSH Terms

Interventions

Metformin

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Sherry Chow, PhD
• Organization: University of Arizona

schow@azcc.arizona.edu

5206263358

Study Officials

• Sherry Chow, PhD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2014
• First Posted: January 7, 2014
• Study Start: March 7, 2014
• Primary Completion: November 30, 2018
• Study Completion: June 14, 2022
• Last Updated: June 27, 2023
• Results First Posted: March 12, 2021

Record last verified: 2023-06

Locations

US (1)