Breast Cancer PreventionPhase 2NCT02028221

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

A Phase 2 study testing Metformin in people with Breast Cancer Prevention, run by University of Arizona at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 21 to 54 years, women only
Conditions the study is for: Breast Cancer Prevention
What is being tested?: Metformin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 151 participants
Where: 1 siteUnited States
Study dates: 7 Mar 2014to 14 Jun 2022
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 54 years
Women only
No healthy volunteers
Adult

Who may be able to join

Premenopausal women
21-54 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:

Show all 12Show fewer

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

Who cannot join

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

Show all 18Show fewer

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
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

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Arizona
Tucson, Arizona, 85719

Other trials in United States

About this study

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.

Read the 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.

A Phase II randomized, double-blind, placebo-controlled trial of metformin in overweight/obese premenopausal women who have metabolic syndrome will be conducted. 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.

Conditions: Breast Cancer Prevention
Being tested: Metformin, Placebo
Keywords: Breast cancer prevention, metformin, Breast cancer risk reduction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MetforminDrug
Also called Glucophage, Glumetza, Fortamet
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.
PlaceboDrug
1 tablet daily by mouth X 4 weeks, then 1 tablet twice daily by mouth for the remaining duration of the trial (12 months)

Study groups in NCT02028221
Study group	Role	What they receive
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) Receives: 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. Receives: Drug: Metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Breast Density at 6 Months
change of dense breast volume at 6 months
Measured: baseline, 6 months
Change in Breast Density at 12 Months
Change in dense breast volume at 12 months
Measured: Baseline, 12 months

Secondary outcomes (7)

Change From Baseline in Serum Insulin Levels at 6 and 12 Months
Measured: baseline, 6 months, 12 months
Change From Baseline in Serum IGF-1 to IGFBP-3 Ratio at 6 and 12 Months
Measured: baseline, 6 months, 12 months
Change From Baseline in Serum Testosterone Levels at 6 and 12 Months
Measured: baseline, 6 months, 12 months
Change From Baseline in Serum Leptin to Adiponectin Ratio at 6 and 12 Months
Measured: baseline, 6 months, 12 months
Change From Baseline in Body Weight at 6 and 12 Months
Measured: baseline, 6 months, 12 months
Change From Baseline in Waist Circumference at 6 and 12 Months
Measured: baseline, 6 months, 12 months
Change From Baseline in Serum IGF-2 Levels at 6 and 12 Months
Measured: baseline, 6 months, 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Mar 201414 Jun 2022

First posted7 Jan 2014 (estimated)
Study start7 Mar 2014
Primary completion30 Nov 2018
Study completion14 Jun 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Breast Cancer PreventionStudies of the same condition, open and under way.
More trials run by University of ArizonaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 151 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02028221
Sponsor's protocol ID: 1300000596
Other IDs: 1R01CA172444-01A1
Status last verified: Jun 2023
First submitted: 2 Jan 2014
Last updated: 27 Jun 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
PubMed 34383179
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.
PubMed 27430256

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Breast Cancer Prevention trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase II Study of Metformin for Reduction of Obesity-Associated Breast Cancer Risk
ClinicalTrials.gov ID: NCT02028221
Acronym / sponsor ID: 1300000596
Conditions: Breast Cancer Prevention
Keywords: Breast cancer prevention, metformin, Breast cancer risk reduction
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 151 participants (actual)
Lead sponsor: University of ArizonaUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: 7 Mar 2014 (actual)
Primary completion: 30 Nov 2018 (actual)
Study completion: 14 Jun 2022 (actual)
First posted: 7 Jan 2014 (estimated)
Results: Posted 12 Mar 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Placebo	Placebo comparator	Drug: Placebo1 tablet daily by mouth X 4 weeks, then 1 tablet twice daily by mouth for the remaining duration of the trial (12 months)
Metformin	Experimental	Drug: Metforminmetformin 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.

Who may qualify

Ages: 21 to 54 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (12 listed)

Premenopausal women
21-54 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.

Key exclusion criteria (18 listed)

Postmenopausal women
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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MetforminAlso: Glucophage, Glumetza, Fortametmetformin 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.	Drug	Metformin
Placebo1 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

Primary outcome

Change in Breast Density at 6 Months
Time frame: baseline, 6 months
change of dense breast volume at 6 months
Change in Breast Density at 12 Months
Time frame: Baseline, 12 months
Change in dense breast volume at 12 months

7 secondary outcomes

Change From Baseline in Serum Insulin Levels at 6 and 12 Months
Time frame: baseline, 6 months, 12 months
Change From Baseline in Serum IGF-1 to IGFBP-3 Ratio at 6 and 12 Months
Time frame: baseline, 6 months, 12 months
Change From Baseline in Serum Testosterone Levels at 6 and 12 Months
Time frame: baseline, 6 months, 12 months
Change From Baseline in Serum Leptin to Adiponectin Ratio at 6 and 12 Months
Time frame: baseline, 6 months, 12 months
Change From Baseline in Body Weight at 6 and 12 Months
Time frame: baseline, 6 months, 12 months
Change From Baseline in Waist Circumference at 6 and 12 Months
Time frame: baseline, 6 months, 12 months
Change From Baseline in Serum IGF-2 Levels at 6 and 12 Months
Time frame: baseline, 6 months, 12 months

Results and safety

Results posted to the registry on 12 Mar 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	75	62
Metformin	76	56

Primary outcome: Change in Breast Density at 6 Months

Time frame: baseline, 6 months. Mean (Standard Deviation). Unit: cm^3

Measure	Placebo n = 41	Metformin n = 38
Value	-5.45 (48.91)	-13.71 (56.69)

Population analysed: Analysis was performed on participants who provided baseline and 6 month breast density measures

Primary outcome: Change in Breast Density at 12 Months

Time frame: Baseline, 12 months. Mean (Standard Deviation). Unit: cm^3

Measure	Placebo n = 43	Metformin n = 39
Value	-12.11 (68.11)	-14.75 (47.84)

Population analysed: Analysis was performed on participants who provided baseline and 12-month breast density measures

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: 12 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	7 of 75 (9.3%)	61 of 75 (81.3%)	0 of 75
Metformin	1 of 76 (1.3%)	67 of 76 (88.2%)	0 of 76

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 34383179Tapia 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.
Derived from this study: PubMed 27430256Martinez 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Sherry Chow, PhD principal investigator

University of Arizona

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Metformin in people with Breast Cancer Prevention, run by University of Arizona at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Breast Density at 6 Months (time frame: baseline, 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02028221, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2023.