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

NCT01905046 | Active Not Recruiting Phase 3 Results DMC

• 3 other identifiers: A211102U10CA031946NCI-2013-00995
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 27

Brief Summary

This randomized phase III trial studies metformin hydrochloride to see how well it 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.

Conditions

Atypical Ductal Breast Hyperplasia; BRCA1 Mutation Carrier; BRCA2 Mutation Carrier; Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  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.

  Up to 24 months

• Test the Reproducibility of RPPM in Duplicate RPPM Determinations From Individual RPFNA Specimens.

  Up to 12 months

• Correlate Baseline RPPM Values With Presence of Atypia at Month 12 and Month 24.

  Up to 24 months

Study Arms (2)

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.

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.

Other: placebo

Interventions

metformin hydrochloride DRUG

given PO

Also known as: 1,1 - dimethylbiguanide hydrochloride, 657-24-9, N, N - dimethylimidodicarbonimidic diamide monohydrochloride

Arm I: metformin hydrochloride

placebo OTHER

given PO

Also known as: PLCB

Arm II: placebo

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Must be at increased risk for breast cancer, defined as at least one of the following four criteria:
• Having had a prior biopsy demonstrating atypical hyperplasia, lobular carcinoma in situ (LCIS), or ductal carcinoma in situ (DCIS)
• A Gail Model Risk of \>= 1.66% over 5 years
• A strong family history of breast and/or ovarian cancer which is defined as at least one of the following:
• One first-degree relative with breast cancer before the age of 50 years
• One first degree relative with bilateral breast cancer
• Two or more first-degree relatives with breast cancer
• One first degree relative and two or more second or third degree relatives with breast cancer
• One first-degree relative with breast cancer and one or more relatives with ovarian cancer
• Two second or third degree relatives with either breast cancer and one or more with ovarian cancer
• One second or third degree relative with breast cancer and two or more with ovarian cancer
• Three or more second or third degree relatives with breast cancer
• Known breast cancer (BRCA)1 or BRCA2 mutation carrier providing that the woman has
• Met with a genetic counselor to review genetic testing results, and
• Has been offered the opportunity to undergo prophylactic mastectomy and oophorectomy

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• Alliance for Clinical Trials in Oncology: lead

Study Sites (27)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Los Angeles County-USC Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

The Community Hospital

Munster, Indiana, 46321, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

Cotton O'Neil Cancer Center / Stormont Vail Health

Topeka, Kansas, 66606, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Prisma Health Cancer Institute - Spartanburg

Boiling Springs, South Carolina, 29316, United States

Location

Prisma Health Cancer Institute - Easley

Easley, South Carolina, 29640, United States

Location

Greenville Health System Cancer Institute-Andrews

Greenville, South Carolina, 29601, United States

Location

Prisma Health Cancer Institute - Butternut

Greenville, South Carolina, 29605, United States

Location

Prisma Health Cancer Institute - Faris

Greenville, South Carolina, 29605, United States

Location

Prisma Health Greenville Memorial Hospital

Greenville, South Carolina, 29605, United States

Location

Prisma Health Cancer Institute - Eastside

Greenville, South Carolina, 29615, United States

Location

Prisma Health Cancer Institute - Greer

Greer, South Carolina, 29650, United States

Location

Prisma Health Cancer Institute - Seneca

Seneca, South Carolina, 29672, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Doctor's Hospital of Laredo

Laredo, Texas, 78041, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Carcinoma, Intraductal, Noninfiltrating; Breast Carcinoma In Situ

Interventions

Metformin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary; Breast Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Victoria Seewaldt, M.D.
• Organization: City of Hope

vseewaldt@coh.org

6262564674

Study Officials

• Victoria Seewaldt, MD

  City of Hope Comprehensive Cancer Center

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2013
• First Posted: July 23, 2013
• Study Start: November 23, 2015
• Primary Completion: November 10, 2023
• Study Completion (Estimated): November 1, 2026
• Last Updated: April 28, 2026
• Results First Posted: April 13, 2025

Record last verified: 2026-04

Locations

US (27)