Breast Atypical Ductal HyperplasiaPhase 3NCT01905046

Metformin Hydrochloride in Preventing Breast Cancer in Patients With Atypical Hyperplasia or In Situ Breast Cancer

A Phase 3 study testing metformin hydrochloride in people with Breast Atypical Ductal Hyperplasia and Breast Ductal Carcinoma In Situ, run by Alliance for Clinical Trials in Oncology at 27 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

This phase III trial studies how well metformin hydrochloride works compared to placebo in preventing breast cancer in patients with atypical hyperplasia or in situ breast cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of metformin hydrochloride may prevent breast cancer. Read more about this study

Who is it for?: Ages 25 to 55 years, women only
Conditions the study is for: Breast Atypical Ductal Hyperplasia, Breast Ductal Carcinoma In Situ, Breast Lobular Carcinoma In Situ
What is being tested?: metformin hydrochloride
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 86 participants
Where: 27 sitesUnited States
Study dates: 23 Nov 2015to Nov 2026
Phase: Phase 3
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 25 to 55 years
Women only
No healthy volunteers
Adult

Who may be able to join

None listed.

Who cannot join

Other active malignancy =< 5 years prior to pre-registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history or prior malignancy, they must not be receiving other specific treatment, i.e., other hormonal therapy, for their cancer
Body mass index (BMI) < 25
Receiving Warfarin
Bilateral breast implants or autologous breast flap reconstruction
Active diagnosis of alcoholism
Contraindication to metformin prevention such as acute hypersensitivity or allergic reaction to metformin

Show all 15Show fewer

Currently receiving tamoxifen or raloxifene
Administration of any investigational agent =< 30 days prior to pre-registration
Previous radiation to both breasts
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Receiving pyrimethamine, cimetidine, rifampin or cephalexin
Women who have a core biopsy or excisional biopsy containing invasive cancer
Women who have taken metformin within the past 90 days
Patients with hemoglobin a1c > 6.3 or who are being actively treated for diabetes

Trial locations and contacts

27 sites in 1 country.

City, postcode or hospital

27 sites in 1 country

United States27 sites

Prisma Health Cancer Institute - Spartanburg
Boiling Springs, South Carolina, 29316
Roswell Park Cancer Institute
Buffalo, New York, 14263
The Christ Hospital
Cincinnati, Ohio, 45219
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27710
Prisma Health Cancer Institute - Easley
Easley, South Carolina, 29640
Greenville Health System Cancer Institute-Andrews
Greenville, South Carolina, 29601
Prisma Health Cancer Institute - Butternut
Greenville, South Carolina, 29605
Prisma Health Cancer Institute - Faris
Greenville, South Carolina, 29605
Prisma Health Greenville Memorial Hospital
Greenville, South Carolina, 29605
Prisma Health Cancer Institute - Eastside
Greenville, South Carolina, 29615
Prisma Health Cancer Institute - Greer
Greer, South Carolina, 29650
M D Anderson Cancer Center
Houston, Texas, 77030
University of Kansas Cancer Center
Kansas City, Kansas, 66160
Doctor's Hospital of Laredo
Laredo, Texas, 78041
Los Angeles County-USC Medical Center
Los Angeles, California, 90033
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53792
The Community Hospital
Munster, Indiana, 46321
Mount Sinai Hospital
New York, New York, 10029
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Prisma Health Cancer Institute - Seneca
Seneca, South Carolina, 29672
City of Hope South Pasadena
South Pasadena, California, 91030
Cotton O'Neil Cancer Center / Stormont Vail Health
Topeka, Kansas, 66606

Other trials in United States

About this study

Official title: Testing for Atypia in Random Periareolar Fine Needle Aspiration (RPFNA) Cytology After 12 Months Metformin (1, 1-Dimethylbiguanide Hydrochloride) Chemoprevention Versus Placebo Control in Premenopausal Women

Read the detailed description

Test for the presence or absence of cytological atypia (as measured by a Masood Cytology Index Score of 14-17) in unilateral or bilateral random periareolar fine needle aspiration (RPFNA) aspirates after 12 and 24 months (24 month is optional for placebo-only group for patients who remain on placebo arm and will not receive metformin [metformin hydrochloride]) for women receiving metformin versus placebo control. The presence of cytological atypia means any atypia in any RPFNA specimen.

SECONDARY OBJECTIVES:

Use the Masood Cytology Index Score to test for the presence of cytological atypia or disappearance of cytological atypia in RPFNA aspirates after 12 months for both arms, and 24 months (24 month is optional for placebo-only group for patients who remain on placebo arm and will not receive metformin, and mandatory for crossover patients) for women receiving metformin 850 mg orally (PO) twice daily (BID) (metformin group).

II. Compare Masood Cytology Score values at 0 and 12 months in right and left breasts (if both breasts were aspirated) from the same individual in the metformin and placebo group.

III. Test the reproducibility of reverse phase protein microarray (RPPM) in duplicate RPPM determinations from individual RPFNA specimens.

IV. Correlate baseline RPPM values with presence of atypia (as measured by Masood Cytology Index Score) at month 12 and month 24 (month 24 optional for placebo-only group; for patients who remain on placebo arm and will not receive metformin) RPFNA.

TERTIARY OBJECTIVES:

Test whether metformin alters RPFNA or blood biomarkers associated with breast cancer risk.

II. Test whether metformin alters markers associated with obesity and insulin resistance.

III. Test other exploratory measures in RPFNA and serum including metformin levels and estrogen/progesterone.

IV. Banking: As part of ongoing research for Alliance Cancer Control studies, banking residual blood and RPFNA products for future studies.

Conditions: Breast Atypical Ductal Hyperplasia, Breast Ductal Carcinoma In Situ, Breast Lobular Carcinoma In Situ
Being tested: metformin hydrochloride, placebo
Medical subject headings: Carcinoma, Intraductal, Noninfiltrating, Breast Carcinoma In Situ

What participants receive

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

metformin hydrochlorideDrug
Also called 1,1 - dimethylbiguanide hydrochloride, 657-24-9, N, N - dimethylimidodicarbonimidic diamide monohydrochloride
given PO
placeboOther
Also called PLCB
given PO

Study groups in NCT01905046
Study group	Role	What they receive
Arm I: metformin hydrochloride	Experimental	Patients receive metformin hydrochloride PO QD or BID for 24 months. Patients will continue metformin 850 mg PO BID for months 13-24. Patients will undergo RPFNA at 24 months. Follow up visits will be performed at 36 and 48 months after the start of treatment. Receives: Drug: metformin hydrochloride
Arm II: placebo	Placebo comparator	Patients receive placebo PO QD or BID for 12 months. Patients may crossover to Arm I for months 13-24. Receives: Other: placebo

What is being measured

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

Test for the Presence or Absence of Cytological Atypia in Unilateral or Bilateral RPFNA Aspirates After 12 Months.
Presence of atypia at 12 months is determined through the average of Masood scores across all evaluable breasts for a patient. If the average score is at least 13.5, then patient will be labeled as having atypia. The primary aim of this study is to compare the presence of atypia at month 12 between two arms using the chi-square test in univariable analysis and regressed on group indicator, age, race, stratification factors, and baseline Masood score using logistic regression in multivariable analysis.
Measured: 12 months

Secondary outcomes (4)

Test for the Masood Score and the Presence of Atypia or Disapperance of Atypia in RPFNA After 12 Months (for Both Arms) and 24 Months for Metformin Arm.
Measured: Up to 24 months
Compare Masood Cytology Score Value at 0 and 12 in Right and Left Breast From the Same Individual in the Metformin and Non-metformin Group.
Measured: Up to 24 months
Test the Reproducibility of RPPM in Duplicate RPPM Determinations From Individual RPFNA Specimens.
Measured: Up to 12 months
Correlate Baseline RPPM Values With Presence of Atypia at Month 12 and Month 24.
Measured: Up to 24 months

Timeline

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

23 Nov 2015Nov 2026

First posted23 Jul 2013 (estimated)
Study start23 Nov 2015
Primary completion10 Nov 2023
Study completionNov 2026 (estimated)

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.
Other trials for Breast Atypical Ductal HyperplasiaStudies of the same condition, open and under way.
More trials run by Alliance for Clinical Trials in OncologyThe 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 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 86 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01905046
Sponsor's protocol ID: A211102
Other IDs: U10CA031946, NCI-2013-00995
Status last verified: Apr 2026
First submitted: 16 Jul 2013
Last updated: 8 Oct 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

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?

See locations

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All Breast Atypical Ductal Hyperplasia trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Testing for Atypia in Random Periareolar Fine Needle Aspiration (RPFNA) Cytology After 12 Months Metformin (1, 1-Dimethylbiguanide Hydrochloride) Chemoprevention Versus Placebo Control in Premenopausal Women
ClinicalTrials.gov ID: NCT01905046
Acronym / sponsor ID: A211102
Conditions: Breast Atypical Ductal Hyperplasia, Breast Ductal Carcinoma In Situ, Breast Lobular Carcinoma In Situ
Phase: Phase 3
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 86 participants (actual)
Lead sponsor: Alliance for Clinical Trials in OncologyUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: 23 Nov 2015 (actual)
Primary completion: 10 Nov 2023 (actual)
Study completion: Nov 2026 (estimated)
First posted: 23 Jul 2013 (estimated)
Results: Posted 13 Apr 2025

Clinical summary

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

Detailed description

Test for the presence or absence of cytological atypia (as measured by a Masood Cytology Index Score of 14-17) in unilateral or bilateral random periareolar fine needle aspiration (RPFNA) aspirates after 12 and 24 months (24 month is optional for placebo-only group for patients who remain on placebo arm and will not receive metformin [metformin hydrochloride]) for women receiving metformin versus placebo control. The presence of cytological atypia means any atypia in any RPFNA specimen.

SECONDARY OBJECTIVES:

Use the Masood Cytology Index Score to test for the presence of cytological atypia or disappearance of cytological atypia in RPFNA aspirates after 12 months for both arms, and 24 months (24 month is optional for placebo-only group for patients who remain on placebo arm and will not receive metformin, and mandatory for crossover patients) for women receiving metformin 850 mg orally (PO) twice daily (BID) (metformin group).

II. Compare Masood Cytology Score values at 0 and 12 months in right and left breasts (if both breasts were aspirated) from the same individual in the metformin and placebo group.

III. Test the reproducibility of reverse phase protein microarray (RPPM) in duplicate RPPM determinations from individual RPFNA specimens.

TERTIARY OBJECTIVES:

Test whether metformin alters RPFNA or blood biomarkers associated with breast cancer risk.

II. Test whether metformin alters markers associated with obesity and insulin resistance.

III. Test other exploratory measures in RPFNA and serum including metformin levels and estrogen/progesterone.

IV. Banking: As part of ongoing research for Alliance Cancer Control studies, banking residual blood and RPFNA products for future studies.

Study design

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

Arm	Type	Receives
Arm I: metformin hydrochloride	Experimental	Drug: metformin hydrochloridePatients receive metformin hydrochloride PO QD or BID for 24 months. Patients will continue metformin 850 mg PO BID for months 13-24. Patients will undergo RPFNA at 24 months. Follow up visits will be performed at 36 and 48 months after the start of treatment.
Arm II: placebo	Placebo comparator	Other: placeboPatients receive placebo PO QD or BID for 12 months. Patients may crossover to Arm I for months 13-24.

Who may qualify

Ages: 25 to 55 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (0 listed)

Key exclusion criteria (15 listed)

Other active malignancy =< 5 years prior to pre-registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history or prior malignancy, they must not be receiving other specific treatment, i.e., other hormonal therapy, for their cancer
Body mass index (BMI) < 25
Receiving Warfarin
Bilateral breast implants or autologous breast flap reconstruction
Active diagnosis of alcoholism

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
metformin hydrochlorideAlso: 1,1 - dimethylbiguanide hydrochloride, 657-24-9, N, N - dimethylimidodicarbonimidic diamide monohydrochloridegiven PO	Drug	Arm I: metformin hydrochloride
placeboAlso: PLCBgiven PO	Other	Arm II: placebo

Primary outcome

Test for the Presence or Absence of Cytological Atypia in Unilateral or Bilateral RPFNA Aspirates After 12 Months.
Time frame: 12 months
Presence of atypia at 12 months is determined through the average of Masood scores across all evaluable breasts for a patient. If the average score is at least 13.5, then patient will be labeled as having atypia. The primary aim of this study is to compare the presence of atypia at month 12 between two arms using the chi-square test in univariable analysis and regressed on group indicator, age, race, stratification factors, and baseline Masood score using logistic regression in multivariable analysis.

4 secondary outcomes

Test for the Masood Score and the Presence of Atypia or Disapperance of Atypia in RPFNA After 12 Months (for Both Arms) and 24 Months for Metformin Arm.
Time frame: Up to 24 months
Compare Masood Cytology Score Value at 0 and 12 in Right and Left Breast From the Same Individual in the Metformin and Non-metformin Group.
Time frame: Up to 24 months
Test the Reproducibility of RPPM in Duplicate RPPM Determinations From Individual RPFNA Specimens.
Time frame: Up to 12 months
Correlate Baseline RPPM Values With Presence of Atypia at Month 12 and Month 24.
Time frame: Up to 24 months

Results and safety

Results posted to the registry on 13 Apr 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Arm I	42	42
Arm II	44	44

Primary outcome: Test for the Presence or Absence of Cytological Atypia in Unilateral or Bilateral RPFNA Aspirates After 12 Months.

Time frame: 12 months. Count of participants. Unit: Participants

Measure	Arm I n = 32	Arm II n = 34
With Aytpia	20	21
Without Aytpia	12	13

Arm I vs Arm II: Odds Ratio (OR): 0.97 (95% CI 0.36 to 2.62), p = 0.951, Chi-squared

Population analysed: Per protocol, evaluable patients are defined as having a baseline Masood score between 14 and 17 in at least one breast, and all evaluable breasts undergo satisfactory RPFNA at 12 months. At the time of the primary analysis, we had 66 evaluable patients out of 86 randomized patients (32 Placebo, 34 Metformin).

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: 24 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Arm I	1 of 42 (2.4%)	24 of 42 (57.1%)	0 of 42
Arm II Months 0-12: Placebo	0 of 44 (0%)	34 of 44 (77.3%)	0 of 44
Arm II Months 13-24: Metformin	2 of 57 (3.5%)	32 of 57 (56.1%)	0 of 57

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

Victoria Seewaldt, MD study chair

City of Hope Medical Center

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

Questions about this trial

What is this clinical trial studying?

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 0 inclusion and 15 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: under way, not looking for participants, as of the sponsor's last update on 8 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 13 Apr 2025). 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?

Test for the Presence or Absence of Cytological Atypia in Unilateral or Bilateral RPFNA Aspirates After 12 Months. (time frame: 12 months). 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 NCT01905046.

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 8 Oct 2026.