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

This study is currently recruiting participants.
Verified August 2017 by Alliance for Clinical Trials in Oncology
Sponsor:
ClinicalTrials.gov Identifier:
NCT01905046
First Posted: July 23, 2013
Last Update Posted: August 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
  Purpose
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.

Condition Intervention Phase
Atypical Ductal Breast Hyperplasia BRCA1 Mutation Carrier BRCA2 Mutation Carrier Ductal Breast Carcinoma in Situ Lobular Breast Carcinoma in Situ Drug: metformin hydrochloride Other: placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Test for the presence or absence of cytological atypia in unilateral or bilateral 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). [ Time Frame: Up to 24 months ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 128
Study Start Date: August 2013
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I: metformin hydrochloride
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
given PO
Other Names:
  • 1,1 - dimethylbiguanide hydrochloride
  • 657-24-9
  • N, N - dimethylimidodicarbonimidic diamide monohydrochloride
Placebo Comparator: Arm II: placebo
Patients receive placebo PO QD or BID for 12 months. Patients may crossover to Arm I for months 13-24.
Other: placebo
given PO
Other Name: PLCB

Detailed 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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   25 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01905046


Contacts
Contact: Victoria Seewaldt, MD (626) 471-7321

Locations
United States, California
City of Hope Comprehensive Cancer Center Recruiting
Duarte, California, United States, 91010
Contact: Victoria L. Seewaldt    800-826-4673    becomingapatient@coh.org   
Principal Investigator: Victoria L. Seewaldt         
United States, Kansas
University of Kansas Cancer Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: Carol J. Fabian    913-945-7552    ctnursenav@kumc.edu   
Principal Investigator: Carol J. Fabian         
United States, Minnesota
Mayo Clinic Suspended
Rochester, Minnesota, United States, 55905
United States, New York
Roswell Park Cancer Institute Suspended
Buffalo, New York, United States, 14263
Columbia University/Herbert Irving Cancer Center Recruiting
New York, New York, United States, 10032
Contact: Katherine D. Crew    212-305-8615      
Principal Investigator: Katherine D. Crew         
United States, North Carolina
Duke University Medical Center Suspended
Durham, North Carolina, United States, 27710
United States, Ohio
The Christ Hospital Recruiting
Cincinnati, Ohio, United States, 45219
Contact: Jennifer B. Manders    513-585-2859      
Principal Investigator: Jennifer B. Manders         
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Lisa D. Yee    800-293-5066    Jamesline@osumc.edu   
Principal Investigator: Lisa D. Yee         
United States, Oklahoma
University of Oklahoma Health Sciences Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: William C. Dooley    405-271-8777    ou-clinical-trials@ouhsc.edu   
Principal Investigator: William C. Dooley         
United States, South Carolina
Greenville Health System Cancer Institute-Easley Recruiting
Easley, South Carolina, United States, 29640
Contact: Jeffrey K. Giguere    864-241-6251      
Principal Investigator: Jeffrey K. Giguere         
Greenville Health System Cancer Institute-Andrews Suspended
Greenville, South Carolina, United States, 29605
Greenville Health System Cancer Institute-Butternut Recruiting
Greenville, South Carolina, United States, 29605
Contact: Jeffrey K. Giguere    864-241-6251      
Principal Investigator: Jeffrey K. Giguere         
Greenville Health System Cancer Institute-Faris Recruiting
Greenville, South Carolina, United States, 29605
Contact: Jeffrey K. Giguere    864-241-6251      
Principal Investigator: Jeffrey K. Giguere         
Greenville Memorial Hospital Recruiting
Greenville, South Carolina, United States, 29605
Contact: Jeffrey K. Giguere    864-241-6251      
Principal Investigator: Jeffrey K. Giguere         
Greenville Health System Cancer Institute-Eastside Recruiting
Greenville, South Carolina, United States, 29615
Contact: Jeffrey K. Giguere    864-241-6251      
Principal Investigator: Jeffrey K. Giguere         
Greenville Health System Cancer Institute-Greer Recruiting
Greer, South Carolina, United States, 29650
Contact: Jeffrey K. Giguere    864-241-6251      
Principal Investigator: Jeffrey K. Giguere         
Greenville Health System Cancer Institute-Seneca Recruiting
Seneca, South Carolina, United States, 29672
Contact: Jeffrey K. Giguere    864-241-6251      
Principal Investigator: Jeffrey K. Giguere         
Greenville Health System Cancer Institute-Spartanburg Recruiting
Spartanburg, South Carolina, United States, 29307
Contact: Jeffrey K. Giguere    864-241-6251      
Principal Investigator: Jeffrey K. Giguere         
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Therese B. Bevers    713-792-3245      
Principal Investigator: Therese B. Bevers         
Doctor's Hospital of Laredo Suspended
Laredo, Texas, United States, 78041
United States, Wisconsin
University of Wisconsin Hospital and Clinics Recruiting
Madison, Wisconsin, United States, 53792
Contact: Lee G. Wilke    877-405-6866      
Principal Investigator: Lee G. Wilke         
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: Victoria Seewaldt, MD City of Hope Comprehensive Cancer Center
  More Information

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT01905046     History of Changes
Other Study ID Numbers: A211102
U10CA031946 ( U.S. NIH Grant/Contract )
NCI-2013-00995 ( Registry Identifier: Clinical Trial Reporting Program )
First Submitted: July 16, 2013
First Posted: July 23, 2013
Last Update Posted: August 17, 2017
Last Verified: August 2017

Additional relevant MeSH terms:
Carcinoma
Hyperplasia
Breast Neoplasms
Carcinoma in Situ
Carcinoma, Ductal, Breast
Breast Carcinoma In Situ
Carcinoma, Intraductal, Noninfiltrating
Carcinoma, Lobular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pathologic Processes
Neoplasms by Site
Breast Diseases
Skin Diseases
Carcinoma, Ductal
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs