Breast Cancer Clinical Trial

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

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.

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Full Description

I. 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:

I. 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:

I. 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.

View Eligibility Criteria

Eligibility Criteria

PRE-REGISTRATION-INCLUSION CRITERIA

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
Pre-menopausal women as defined as four menstrual cycles within the last six months prior to pre-registration; women with less than 4 menses within 6 months prior to pre-registration, or women who have had a hysterectomy with ovaries intact will be considered premenopausal if follicle-stimulating hormone (FSH) level is < 20; women who are using hormonal contraceptives that cause amenorrhea (e.g. injectable and extended oral contraceptives, hormone containing contraceptive ring, or hormone containing intrauterine device) will be considered eligible if they had a minimum of 4 menstrual cycles within the last six months prior to starting on the contraceptive
Digital mammogram within 365 days prior to pre-registration
Mammograms must be read as not suspicious for breast cancer (American College of Rheumatology [ACR] class I-III); subjects with a class IV mammogram may be enrolled once they have been evaluated by a breast surgeon and there is no evidence of invasive malignancy
Must be non-pregnant and non-lactating for at least one year prior to pre-registration
If currently menstruating, subjects must use a reliable method of birth control
Willing to provide RPFNA and blood samples for correlative research purposes
REGISTRATION/RANDOMIZATION INCLUSION CRITERIA:

Qualifying cytological atypia in RPFNA, Masood score of 14-17; the qualifying RPFNA (of one or both breasts) must be send to Dr. Seewaldt's laboratory for cytological scoring and proteomic analysis; score results must be received from Dr. Seewaldt's lab prior to patient registration/randomization; test must be done =< 90 days prior to registration/randomization

* Note: Only the contralateral breast can be aspirated in women with DCIS and those undergoing surgery for an atypical lesion; the decision to aspirate the contralateral breast is at the discretion of the woman's surgeon

Hemoglobin >= 9 g/dL
Absolute neutrophil count (ANC) >= 1500/mm^3
Platelet count >= 75,000/mm^3
Creatinine =< 1.4 mg/dL
Total bilirubin =< 3.0 mg/dL
Aspartate transaminase (AST) =< 3 x upper limit of normal (ULN)
Alanine transaminase (ALT) =< 3 x ULN

Negative pregnancy test done =< 7 days prior to registration/randomization, for women of childbearing potential only

* A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)

Women eligible to take tamoxifen must be offered tamoxifen prevention as part of their clinical care and have refused tamoxifen treatment

Exclusion Criteria

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

Study is for people with:

Breast Cancer

Phase:

Phase 3

Estimated Enrollment:

161

Study ID:

NCT01905046

Recruitment Status:

Active, not recruiting

Sponsor:

Alliance for Clinical Trials in Oncology

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There are 24 Locations for this study

See Locations Near You

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

How clear is this clinincal trial information?

Study is for people with:

Breast Cancer

Phase:

Phase 3

Estimated Enrollment:

161

Study ID:

NCT01905046

Recruitment Status:

Active, not recruiting

Sponsor:


Alliance for Clinical Trials in Oncology

How clear is this clinincal trial information?

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