AzTrials
AzTrials

Breast CancerPhase 3NCT01101438

A Phase III Randomized Trial of Metformin vs Placebo in Early Stage Breast Cancer

A Phase 3 study testing metformin hydrochloride in people with Breast Cancer, run by Canadian Cancer Trials Group at 344 sites in 4 countries.

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

This study is looking at whether Metformin, an agent that is commonly used to treat diabetes, can decrease or affect the ability of breast cancer cells to grow and whether Metformin will work with other therapies to keep cancer from recurring. Read more about this study

Who is it for?
Ages 18 to 74 years
Conditions the study is for
Breast Cancer
What is being tested?
metformin hydrochloride
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
3,649 participants
Where
344 sitesin 4 countries
Study dates
13 Aug 2010to 18 Aug 2023
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 18 to 74 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Eligibility Criteria:

  • Subjects must have histologically confirmed invasive breast cancer and be enrolled in the trial within 12 months after the first histologic diagnosis of invasive breast cancer. A core biopsy interpreted as invasive cancer meets this criterion; otherwise, the date of first histologic diagnosis will be the date of first surgical procedure that identifies invasive cancer (biopsy, lumpectomy or mastectomy). Neoadjuvant subjects should have no evidence of clinical T4 disease prior to chemotherapy and surgery. Bilateral breast carcinoma is allowed provided diagnoses are synchronous - that is, within 3 months of one another - and at least one of the two breast carcinomas meet the eligibility criteria and neither violates the eligibility criteria.
  • All subjects (both adjuvant and neo-adjuvant) must have sentinel lymph node biopsy and/or axillary lymph node dissection.

Sentinel lymph node biopsy alone is allowed in the following instances:

  1. sentinel lymph node biopsy is negative: pN0
  2. sentinel lymph node biopsy is positive for isolated tumour cells only: pN0 (i+)
  3. * clinically node negative, T1-2 tumours with sentinel lymph node biopsy positive in ≤ 2 lymph nodes without extra-capsular extension or matted nodes and undergoing breast conserving surgery and tangential whole breast irradiation (* excludes subjects treated with neo-adjuvant systemic therapy)

Definitive surgery and/or chemotherapy have been completed at least 4 weeks prior to randomization. Surgical margins must be clear of invasive carcinoma. If there is microscopic residual ductal in situ disease present at lumpectomy or total mastectomy margins, further excision is highly recommended. If further excision is not undertaken, the subject may still be entered on study, provided that in addition to breast or chest wall irradiation, a boost to the tumour bed is delivered. In situ lobular disease at the margin is acceptable.

Adjuvant subjects with the following pT pN combinations are eligible:

  • pT1c, pN0 AND negative estrogen and progesterone receptors AND HER2 negative OR
  • pT2N0 and at least one of the following tumour characteristics: histologic grade 3, lymphovascular invasion, negative estrogen and progesterone receptors, HER2 positive, Oncotype Dx recurrence score ≥ 25 (or if Oncotype Dx recurrence score is not available, Ki67 > 14%) OR
  • Subjects with pT3, pN0 OR
  • Subjects with pT1-3, pN1-3

The eligibility of neo-adjuvant subjects is assessed on the basis of cTNM. The same eligible TNM combinations apply.

  • HER2 status must be known. (Positive = 3+ over-expression by IHC in > 30% of invasive tumour cells OR HER2 gene amplification by FISH/CISH > 6 HER2 gene copies per nucleus, OR a FISH/CISH ratio: HER2 gene copies to chromosome 17 signals of ≥ 2.2. All other results will be considered negative).
  • Patients must have had a bilateral mammogram within 12 months prior to randomization, unless the initial surgery was a total mastectomy, in which case only a mammogram of the remaining breast is required. (Subjects with bilateral total mastectomies and no mammogram within 12 months prior to randomization must, instead, have a physical examination of the chest wall to ensure there is no residual or recurrent disease at the time of randomization. The date of this examination is used in place of the mammogram date on the eligibility checklist.)
  • Investigations, including chest X-ray or CT chest, bone scan (with radiographs of suspicious areas) and abdominal ultrasound or liver scan or CT abdomen have been performed between the first histologic diagnosis and the time of randomization.
  • Chest X-Ray, 2 view (or Chest CT) is mandatory
  • Bone scans (with x-rays of abnormal areas) are required only if there are signs or symptoms of metastatic disease
  • Abdominal imaging is required only if there are signs or symptoms of metastatic disease
  • Hematology investigations (WBC, Granulocytes, Platelets, Hemoglobin) have been completed within 28 days prior to randomization and results are available.
  • Biochemistry investigations have been completed within 28 days prior to randomization and values are within the parameters required by the protocol.

AST < 1.8 X ULN; ALT < 1.8 X ULN; Alkaline Phosphatase < 2 X ULN; Serum Creatinine < 115 μmol/L (1.3mg/dL) Serum Bilirubin < institution ULN (except for subjects with Gilbert's Disease who are eligible despite elevated serum bilirubin level)

  • ECOG Performance Status of 0,1 or 2 (at baseline evaluation visit within 28 days prior to randomization).
  • Age ≥ 18 and < 75 and life expectancy of at least 5 years (18 years of age was used as a cut-off due to the lack of data indicating that breast cancer is a health issue in the < 18 years age group and metformin safety in pediatric patients has not been confirmed. Age > 80 carries increased risk of lactic acidosis and study intervention is for 5 years).
  • Subjects must be accessible for treatment and follow-up. Investigators must assure themselves the subjects randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
  • In accordance with NCIC CTG policy, protocol treatment is to begin within 10 working days of patient randomization.
  • Subject consent must be obtained according to local Institutional and/or University Human Experimentation Committee requirements. It will be the responsibility of the local participating investigators to obtain the necessary local clearance, and to indicate in writing to the NCIC CTG Study Coordinator that such clearance has been obtained, before the trial can commence in that centre. Because of differing requirements, a standard consent form for the trial will not be provided but a sample form is given. A copy of the initial full board REB approval and approved consent form must be sent to the central office. The patient must sign the consent form prior to randomization or registration. Please note that the consent form for this study must contain a statement which gives permission for the NCIC CTG and monitoring agencies to review patient records (see Section 16 for further details).

For the first 888 eligible English or French-speaking subjects only (sub-set enrollment completed 2011NOV04):

  • Subject is able (i.e. sufficiently fluent) and willing to complete the Quality of Life (EORTC QLQ C-30 and Trial Specific Checklist) in English or French. The baseline assessment must already have been completed at the time of enrollment. Inability (illiteracy in English or French, loss of sight or other equivalent reason) to complete questionnaires will not make the patient ineligible for the study; however, ability but unwillingness to complete the questionnaires will make the patient ineligible. (Once the target number of 888 subjects is achieved, this criterion will no longer need to be fulfilled.) [See Appendix VI]. Sub-set enrollment completed 2011NOV04.
  • English-speaking subjects who have completed the Quality of Life Questionnaire who are able (i.e. sufficiently fluent) and willing to complete Nurses Health Study II Physical Activity Questionnaire and Block Alive Screener in English. The baseline assessment must already have been completed at the time of enrollment. Inability (illiteracy in English, loss of sight or other equivalent reason) to complete questionnaires will not make the patient ineligible for the study; however, ability but unwillingness to complete the questionnaires will make the patient ineligible. (This component of the study will close at the same time as the Quality Of Life sub-study.) Closed to new patient enrollment as of 2011NOV04.

Ineligibility Criteria:

  • Subjects with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years.
  • Subjects with locally recurrent or metastatic breast carcinoma. (Subjects with prior invasive breast cancer at any time are not eligible. Subjects with prior DCIS only in either breast are eligible provided the DCIS has been curatively treated including surgery, radiotherapy and/or Tamoxifen).
  • Subjects whose axillary node status is unknown.
  • Known diabetes (type 1 or 2) or baseline fasting glucose > 7.0 mmol/L (126 mg/dL). (Sampled and assayed according to local institution's procedures.)
  • Known hypersensitivity or intolerance to metformin.
  • Any condition associated with increased risk of metformin-associated lactic acidosis (e.g. congestive heart failure defined as New York Heart Association {NYHA} Class III or IV functional status [see Appendix IX], history of acidosis of any type; habitual * Currently taking metformin, sulfonylureas, thiazolidinediones or insulin for any reason.
  • Current or planned pregnancy or lactation in women of child-bearing potential. Men should not father a child. (An effective method of birth control should be used while on study treatment which could include abstinence, IUD, condoms or other barrier methods of birth control because the safety of metformin in pregnancy or in male fertility has not been established).
  • Concurrent or planned participation in randomized trials of weight loss or exercise interventions or trials targeting insulin, IGF-1 or their receptors, or involving P13K inhibitors (at the time of randomization)*.
  • These interventions would interfere with the primary endpoint. (Also, in general, double randomizations in breast cancer trials for MA.32 patients are permitted only if the patient meets all the eligibility criteria for MA.32 and the sponsor of the previous trial has no objection to the patient also being enrolled in MA.32).

Trial locations and contacts

344 sites in 4 countries.

344 sites in 4 countries

United States280 sites

  • Akron City Hospital

    Akron, Ohio, 44304

  • Akron General Medical Center

    Akron, Ohio, 44307

  • Phoebe Putney Memorial Hospital

    Albany, Georgia, 31701

  • University of New Mexico

    Albuquerque, New Mexico, 87106

  • Presbyterian Kaseman Hospital

    Albuquerque, New Mexico, 87110

  • McFarland Clinic

    Ames, Iowa, 50010

  • Providence Alaska Medical Center

    Anchorage, Alaska, 99508

  • AnMed Health Cancer Center

    Anderson, South Carolina, 29621

  • University of Michigan Health System-Cancer Center

    Ann Arbor, Michigan, 48109

  • Kaiser Permanente-Deer Valley Medical Center

    Antioch, California, 94531

  • Mission Hospitals Inc

    Asheville, North Carolina, 28801

  • University of Colorado Cancer Center - Anschutz Cancer Pavilion

    Aurora, Colorado, 80045

  • Rush - Copley Medical Center

    Aurora, Illinois, 60504

  • University Medical Center Brackenridge

    Austin, Texas, 78701

  • University of Maryland Greenebaum Cancer Center

    Baltimore, Maryland, 21201-1595

  • Mercy Medical Center

    Baltimore, Maryland, 21202

  • Johns Hopkins University

    Baltimore, Maryland, 21287-8936

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • Mary Bird Perkins Cancer Center

    Baton Rouge, Louisiana, 70809

  • Battle Creek Health System

    Battle Creek, Michigan, 49017

  • Alta Bates Summit Medical Center-Herrick Campus

    Berkeley, California, 94704

  • Mountainview Medical

    Berlin Corners, Vermont, 05602

  • Suburban Hospital

    Bethesda, Maryland, 20814

  • Medcenter One Health Systems

    Bismarck, North Dakota, 58501

  • Mid Dakota Clinic

    Bismarck, North Dakota, 58501

  • Boca Raton Regional Hospital

    Boca Raton, Florida, 33486

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • State University of New York Downstate Medical Center

    Brooklyn, New York, 11203

  • Maimonides Medical Center

    Brooklyn, New York, 11219

  • Coney Island Hospital

    Brooklyn, New York, 11235

  • Bryn Mawr Hospital

    Bryn Mawr, Pennsylvania, 19010

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Lahey Clinic Medical Center

    Burlington, Massachusetts, 01805

  • University of Vermont

    Burlington, Vermont, 05401

  • Aultman Health Foundation

    Canton, Ohio, 44710

  • Oncology Associates at Mercy Medical Center

    Cedar Rapids, Iowa, 52403

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Presbyterian Hospital

    Charlotte, North Carolina, 28204

  • Martha Jefferson Hospital

    Charlottesville, Virginia, 22901

  • Saint Luke's Hospital

    Chesterfield, Missouri, 63017

  • Mount Sinai Hospital Medical Center

    Chicago, Illinois, 60608

  • John H Stroger Jr Hospital of Cook County

    Chicago, Illinois, 60612-3785

  • Swedish Covenant Hospital

    Chicago, Illinois, 60625

  • Resurrection Healthcare

    Chicago, Illinois, 60631

  • University of Chicago

    Chicago, Illinois, 60637-1470

  • Enloe Medical Center

    Chico, California, 95926

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • MetroHealth Medical Center

    Cleveland, Ohio, 44109

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Memorial Hospital Colorado Springs

    Colorado Springs, Colorado, 80909

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

  • New Hampshire Oncology-Hematology PA

    Concord, New Hampshire, 03301

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Heartland Oncology and Hematology LLP

    Council Bluffs, Iowa, 51503

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822-2001

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Kaiser Permanente-Franklin

    Denver, Colorado, 80205

  • Wayne State University

    Detroit, Michigan, 48202

  • Duluth Clinic CCOP

    Duluth, Minnesota, 55805

  • Hematology Oncology Associates of Central New York PC

    East Syracuse, New York, 13057

  • Marshfield Clinic Cancer Care at Regional Cancer Center

    Eau Claire, Wisconsin, 54701

  • Fairview-Southdale Hospital

    Edina, Minnesota, 55435

  • Elkhart Clinic

    Elkhart, Indiana, 46514-2098

  • Michiana Hematology Oncology PC-Elkhart

    Elkhart, Indiana, 46514

  • Elmhurst Memorial Hospital

    Elmhurst, Illinois, 60126

  • Evanston CCOP-NorthShore University HealthSystem

    Evanston, Illinois, 60201

  • Saint Francis Hospital

    Evanston, Illinois, 60202

  • Fairbanks Memorial Hospital

    Fairbanks, Alaska, 99701

  • Sanford Clinic North-Fargo

    Fargo, North Dakota, 58102

  • Sanford Medical Center-Fargo

    Fargo, North Dakota, 58122

  • University of Connecticut

    Farmington, Connecticut, 06030

  • McLeod Regional Medical Center

    Florence, South Carolina, 29506

  • Central Wisconsin Cancer Program

    Fond du Lac, Wisconsin, 54935

  • Poudre Valley Hospital

    Fort Collins, Colorado, 80524

  • Front Range Cancer Specialists

    Fort Collins, Colorado, 80528

  • Frederick Memorial Hospital

    Frederick, Maryland, 21701

  • Unity Hospital

    Fridley, Minnesota, 55432

  • Northeast Georgia Medical Center

    Gainesville, Georgia, 30501

  • Glendale Memorial Hospital and Health Center

    Glendale, California, 91204

  • Addison Gilbert Hospital

    Gloucester, Massachusetts, 01930

  • Wayne Memorial Hospital

    Goldsboro, North Carolina, 27534

  • Altru Cancer Center

    Grand Forks, North Dakota, 58201

  • Grand Rapids Clinical Oncology Program

    Grand Rapids, Michigan, 49503

  • Saint Mary's Health Care

    Grand Rapids, Michigan, 49503

  • Spectrum Health at Butterworth Campus

    Grand Rapids, Michigan, 49503

  • Saint Vincent Hospital

    Green Bay, Wisconsin, 54301

  • Aurora BayCare Medical Center

    Green Bay, Wisconsin, 54311-6519

  • Greenwich Hospital

    Greenwich, Connecticut, 06830

  • Hartford Hospital

    Hartford, Connecticut, 06102

  • Ingalls Memorial Hospital

    Harvey, Illinois, 60426

  • Kaiser Permanente, Hayward

    Hayward, California, 94545

  • Margaret R Pardee Memorial Hospital

    Hendersonville, North Carolina, 28791

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • High Point Regional Hospital

    High Point, North Carolina, 27261

  • University of Hawaii

    Honolulu, Hawaii, 96813

  • Kaiser Permanente Moanalua Medical Center

    Honolulu, Hawaii, 96819

  • New Hampshire Oncology Hematology Associates

    Hooksett, New Hampshire, 03106

  • Edwards Comprehensive Cancer Center

    Huntington, West Virginia, 25701

  • Indiana University Hospital/Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • Good Samaritan Hospital

    Kearney, Nebraska, 68847

  • Kettering Medical Center

    Kettering, Ohio, 45429

  • Kinston Medical Specialists PA

    Kinston, North Carolina, 28501

  • University of Tennessee - Knoxville

    Knoxville, Tennessee, 37920

  • Howard Regional Healthcare System

    Kokomo, Indiana, 46904

  • Gundersen Lutheran Health System/CCOP

    La Crosse, Wisconsin, 54601

  • Moores University of California San Diego Cancer Center

    La Jolla, California, 92093

  • LRGHealthcare-Lakes Region General Hospital

    Laconia, New Hampshire, 03246

  • Monter Cancer Center

    Lake Success, New York, 11042

  • The Watson Clinic

    Lakeland, Florida, 33805

  • Lancaster General Hospital

    Lancaster, Pennsylvania, 17604

  • Doctor's Hospital of Laredo

    Laredo, Texas, 78045

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • Central Baptist Hospital

    Lexington, Kentucky, 40503

  • Lincoln Medical Education Foundation Cancer Resource Center

    Lincoln, Nebraska, 68510

  • Saint Barnabas Medical Center

    Livingston, New Jersey, 07039

  • The Dana-Farber Cancer Institute at Londonderry

    Londonderry, New Hampshire, 03053

  • Long Beach Memorial Medical Center-Todd Cancer Institute

    Long Beach, California, 90806

  • Saint John Medical Center

    Longview, Washington, 98632

  • University of Southern California

    Los Angeles, California, 90033-0804

  • University of California at Los Angeles (UCLA )

    Los Angeles, California, 90095

  • Lowell General Hospital

    Lowell, Massachusetts, 01854

  • Lynchburg Hematology-Oncology Clinic

    Lynchburg, Virginia, 24501

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • North Shore University Hospital CCOP

    Manhasset, New York, 11030

  • North Shore University Hospital

    Manhasset, New York, 11030

  • Minnesota Oncology Hematology PA-Maplewood

    Maplewood, Minnesota, 55109

  • Saint John's Hospital - Healtheast

    Maplewood, Minnesota, 55109

  • Marshfield Clinic

    Marshfield, Wisconsin, 54449

  • Fremont - Rideout Cancer Center

    Marysville, California, 95901

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • Columbia Saint Mary's Hospital - Ozaukee

    Mequon, Wisconsin, 53097

  • Mount Sinai Medical Center CCOP

    Miami Beach, Florida, 33140

  • Saint Anthony Memorial Health Center

    Michigan City, Indiana, 46360

  • Wheaton Franciscan Healthcare - Saint Joseph

    Milwaukee, Wisconsin, 53210

  • Columbia Saint Mary's Water Tower Medical Commons

    Milwaukee, Wisconsin, 53211

  • Abbott-Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • Marshfield Clinic-Minocqua Center

    Minocqua, Wisconsin, 54548

  • Trinity Cancer Care Center

    Minot, North Dakota, 58701

  • Michiana Hematology Oncology PC-Mishawaka

    Mishawaka, Indiana, 46545-1470

  • Trinity Medical Center

    Moline, Illinois, 61265

  • West Virginia University

    Morgantown, West Virginia, 26506

  • Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County

    Mount Holly, New Jersey, 08060

  • Mount Kisco Medical Group at Northern Westchester Hospital

    Mount Kisco, New York, 10549-3417

  • Mount Kisco Medical Group

    Mount Kisco, New York, 10549

  • Mercy Health Partners-Mercy Campus

    Muskegon, Michigan, 49444

  • Vanderbilt Breast Center at One Hundred Oaks

    Nashville, Tennessee, 37204

  • Vanderbilt University

    Nashville, Tennessee, 37232

  • Yale University

    New Haven, Connecticut, 06520-8032

  • Long Island Jewish Medical Center

    New Hyde Park, New York, 11040

  • Beth Israel Medical Center

    New York, New York, 10003

  • New York University Langone Medical Center

    New York, New York, 10016

  • Saint Luke's Roosevelt Hospital Center - Saint Luke's Division

    New York, New York, 10025

  • Mount Sinai Medical Center

    New York, New York, 10029

  • Columbia University Medical Center

    New York, New York, 10032

  • Michiana Hematology Oncology PC-Niles

    Niles, Michigan, 49120

  • Bay Area Tumor Institution CCOP

    Oakland, California, 94609

  • Kaiser Permanente-Oakland

    Oakland, California, 94611

  • Missouri Valley Cancer Consortium CCOP

    Omaha, Nebraska, 68106

  • Methodist Estabrook Cancer Center

    Omaha, Nebraska, 68114

  • University of California Medical Center At Irvine-Orange Campus

    Orange, California, 92868

  • Florida Hospital

    Orlando, Florida, 32803

  • Ottumwa Regional Health Center

    Ottumwa, Iowa, 52501

  • Owensboro Mercy Medical Center

    Owensboro, Kentucky, 42303

  • Paoli Memorial Hospital

    Paoli, Pennsylvania, 19301

  • Singing River Hospital

    Pascagoula, Mississippi, 39581

  • Memorial Hospital of Rhode Island

    Pawtucket, Rhode Island, 02860

  • Illinois CancerCare-Peoria

    Peoria, Illinois, 61615

  • Illinois Oncology Research Association CCOP

    Peoria, Illinois, 61615

  • Pennsylvania Hospital

    Philadelphia, Pennsylvania, 19107

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111-2497

  • Albert Einstein Medical Center

    Philadelphia, Pennsylvania, 19141

  • Phoenixville Hospital

    Phoenixville, Pennsylvania, 19460

  • FirstHealth of the Carolinas-Moore Regional Hosiptal

    Pinehurst, North Carolina, 28374

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15232

  • Michiana Hematology Oncology PC-Plymouth

    Plymouth, Indiana, 46563

  • Pomona Valley Hospital Medical Center

    Pomona, California, 91767

  • Legacy Good Samaritan Hospital and Medical Center

    Portland, Oregon, 97210

  • Columbia River Oncology Program

    Portland, Oregon, 97225

  • Kaiser Permanente

    Portland, Oregon, 97227

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Kansas City CCOP

    Prairie Village, Kansas, 66208

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Women and Infants Hospital

    Providence, Rhode Island, 02905

  • Rex Cancer Center

    Raleigh, North Carolina, 27607

  • Rapid City Regional Hospital

    Rapid City, South Dakota, 57701

  • Saint Joseph Medical Center

    Reading, Pennsylvania, 19605

  • Kaiser Permanente-Redwood City

    Redwood City, California, 94063

  • Kaiser Permanente-Richmond

    Richmond, California, 94801

  • Valley Hospital

    Ridgewood, New Jersey, 07450

  • North Memorial Medical Health Center

    Robbinsdale, Minnesota, 55422

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Rochester General Hospital

    Rochester, New York, 14621

  • Kaiser Permanente-Roseville

    Roseville, California, 95661

  • William Beaumont Hospital

    Royal Oak, Michigan, 48073

  • University of California Davis-Cancer Center

    Sacramento, California, 95817

  • Kaiser Permanente-South Sacramento

    Sacramento, California, 95823

  • Kaiser Permanente - Sacramento

    Sacramento, California, 95825

  • CentraCare Clinic

    Saint Cloud, Minnesota, 56303

  • Marie Yeager Cancer Center

    Saint Joseph, Michigan, 49085

  • Metro-Minnesota CCOP

    Saint Louis Park, Minnesota, 55416

  • Park Nicollet Clinic - Saint Louis Park

    Saint Louis Park, Minnesota, 55416

  • Regions Hospital

    Saint Paul, Minnesota, 55101

  • United Hospital

    Saint Paul, Minnesota, 55102

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • University of Texas Health Science Center

    San Antonio, Texas, 78229-3900

  • Kaiser Permanente-Mission

    San Diego, California, 92108

  • Kaiser Permanente

    San Diego, California, 92108

  • Kaiser Permanente-San Francisco

    San Francisco, California, 94115

  • University of California San Francisco Medical Center-Mount Zion

    San Francisco, California, 94115

  • Kaiser Permanente-Santa Teresa-San Jose

    San Jose, California, 95119

  • Kaiser Permanente-San Rafael

    San Rafael, California, 94903

  • Kaiser Permanente Medical Center - Santa Clara

    Santa Clara, California, 95051

  • Kaiser Permanente-Santa Rosa

    Santa Rosa, California, 95403

  • Pinnacle Oncology Associates

    Scottsdale, Arizona, 85258

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • Virginia Mason CCOP

    Seattle, Washington, 98101

  • Pacific Medical Center-First Hill

    Seattle, Washington, 98104

  • Group Health Cooperative

    Seattle, Washington, 98112

  • Swedish Medical Center-First Hill

    Seattle, Washington, 98122-4307

  • University of Washington Medical Center

    Seattle, Washington, 98195

  • Siouxland Hematology Oncology Associates

    Sioux City, Iowa, 51101

  • Sanford Clinic

    Sioux Falls, South Dakota, 57104

  • Avera Cancer Institute

    Sioux Falls, South Dakota, 57105

  • Michiana Hematology Oncology PC-South Bend

    South Bend, Indiana, 46601

  • Kaiser Permanente-South San Francisco

    South San Francisco, California, 94080

  • Spartanburg Regional Medical Center

    Spartanburg, South Carolina, 29303

  • Rockwood Clinic

    Spokane, Washington, 99220

  • Memorial Medical Center

    Springfield, Illinois, 62781-0001

  • Saint John's Hospital

    Springfield, Missouri, 65804

  • Cox Medical Center

    Springfield, Missouri, 65807

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Missouri Baptist Medical Center

    St Louis, Missouri, 63131

  • Saint John's Mercy Medical Center

    St Louis, Missouri, 63141

  • Saint Louis-Cape Girardeau CCOP

    St Louis, Missouri, 63141

  • Stamford Hospital

    Stamford, Connecticut, 06904

  • Stanford University

    Stanford, California, 94305

  • Mount Nittany Medical Center

    State College, Pennsylvania, 16803

  • Kaiser Permanente-Stockton

    Stockton, California, 95210

  • Stony Brook University Medical Center

    Stony Brook, New York, 11794

  • Aurora Medical Center in Summit

    Summit, Wisconsin, 53066

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

  • Northwest CCOP

    Tacoma, Washington, 98405

  • Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

  • Albert Einstein College of Medicine

    The Bronx, New York, 10461

  • The North Division of Montefiore Medical Center

    The Bronx, New York, 10466

  • Montefiore Medical Center

    The Bronx, New York, 10467-2490

  • Connecticut Oncology and Hematology LLP

    Torrington, Connecticut, 06790

  • Munson Medical Center

    Traverse City, Michigan, 49684

  • Tahoe Forest Cancer Center

    Truckee, California, 96161

  • Arizona Cancer Center at University Medical Center North

    Tucson, Arizona, 85719

  • University of Arizona Health Sciences Center

    Tucson, Arizona, 85724

  • Carle Foundation - Carle Cancer Center

    Urbana, Illinois, 61801

  • Kaiser Permanente Medical Center-Vacaville

    Vacaville, California, 95688

  • South Georgia Medical Center

    Valdosta, Georgia, 31602

  • Kaiser Permanente-Vallejo

    Vallejo, California, 94589

  • Providence Saint Mary Regional Cancer Center

    Walla Walla, Washington, 99362

  • Kaiser Permanente-Walnut Creek

    Walnut Creek, California, 94596

  • John Muir Medical Center

    Walnut Creek, California, 94598

  • Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • Washington Hospital Center

    Washington D.C., District of Columbia, 20010

  • Sibley Memorial Hospital

    Washington D.C., District of Columbia, 20016

  • Wenatchee Valley Medical Center

    Wenatchee, Washington, 98801

  • Chester County Hospital

    West Chester, Pennsylvania, 19380

  • Marshfield Clinic - Weston Center

    Weston, Wisconsin, 54476

  • Michiana Hematology Oncology-PC Westville

    Westville, Indiana, 46391

  • Wheeling Hospital

    Wheeling, West Virginia, 26003

  • Wichita CCOP

    Wichita, Kansas, 67214

  • Rice Memorial Hospital

    Willmar, Minnesota, 56201

  • Forsyth Memorial Hospital

    Winston-Salem, North Carolina, 27103

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

  • Minnesota Oncology and Hematology PA-Woodbury

    Woodbury, Minnesota, 55125

  • Saint Vincent Hospital - Fallon Clinic

    Worcester, Massachusetts, 01608

  • Lankenau Hospital

    Wynnewood, Pennsylvania, 19096

  • Metro Health Hospital

    Wyoming, Michigan, 49519

  • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital

    Yakima, Washington, 98902

  • York Hospital

    York Village, Maine, 03909

Other trials in United States

Canada41 sites

  • BCCA - Abbotsford Centre

    Abbotsford British Columbia, British Columbia, V2S 0C2

  • Cambridge Memorial Hospital

    Cambridge, Ontario, N1R 3G2

  • PEI Cancer Treatment Centre,Queen Elizabeth Hospital

    Charlottetown, Prince Edward Island, C1A 8T5

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • Northeast Cancer Center Health Sciences

    Greater Sudbury, Ontario, P3E 5J1

  • Hopital Charles LeMoyne

    Greenfield Park, Quebec, J4V 2H1

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • BCCA - Cancer Centre for the Southern Interior

    Kelowna, British Columbia, V1Y 5L3

  • Cancer Centre of Southeastern Ontario at Kingston

    Kingston, Ontario, K7L 5P9

  • Grand River Regional Cancer Centre

    Kitchener, Ontario, N2G 1G3

  • Hopital de la Cite-de-la-Sante

    Laval, Quebec, H7M 3L9

  • London Regional Cancer Program

    London, Ontario, N6A 4L6

  • Credit Valley Hospital

    Mississauga, Ontario, L5M 2N1

  • The Moncton Hospital

    Moncton, New Brunswick, E1C 6Z8

  • The Vitalite Health Network - Dr. Leon Richard

    Moncton, New Brunswick, E1C 8X3

  • Hopital Maisonneuve-Rosemont

    Montreal, Quebec, H1T 2M4

  • McGill University - Dept. Oncology

    Montreal, Quebec, H2W 1S6

  • CHUM - Hotel Dieu du Montreal

    Montreal, Quebec, H2W 1T8

  • Stronach Regional Health Centre at Southlake

    Newmarket, Ontario, L3Y 2P9

  • Lakeridge Health Oshawa

    Oshawa, Ontario, L1G 2B9

  • Ottawa Health Research Institute - General Division

    Ottawa, Ontario, K1H 8L6

  • CHUQ-Pavillon Hotel-Dieu de Quebec

    Québec, Quebec, G1R 2J6

  • CHA-Hopital Du St-Sacrement

    Québec, Quebec, G1S 4L8

  • Allan Blair Cancer Centre

    Regina, Saskatchewan, S4T 7T1

  • Atlantic Health Sciences Corporation

    Saint John, New Brunswick, E2L 4L2

  • Saskatoon Cancer Centre

    Saskatoon, Saskatchewan, S7N 4H4

  • Algoma District Cancer Program

    Sault Ste. Marie, Ontario, P6B 0A8

  • Niagara Health System

    St. Catharines, Ontario, L2R 7C6

  • Dr. H. Bliss Murphy Cancer Centre

    St. John's, Newfoundland and Labrador, AIB 3V6

  • BCCA - Fraser Valley Cancer Centre

    Surrey, British Columbia, V3V 1Z2

  • Thunder Bay Regional Health Science Centre

    Thunder Bay, Ontario, P7B 6V4

  • Toronto East General Hospital

    Toronto, Ontario, M4C 3E7

  • Odette Cancer Centre

    Toronto, Ontario, M4N 3M5

  • St. Michael's Hospital

    Toronto, Ontario, M5B 1W8

  • Mount Sinai Hospital

    Toronto, Ontario, M5G 1X5

  • Univ. Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

  • Trillium Health Centre - West Toronto

    Toronto, Ontario, M9C 1A5

  • BCCA - Vancouver Cancer Centre

    Vancouver, British Columbia, V5Z 4E6

  • BCCA - Vancouver Island Cancer Centre

    Victoria, British Columbia, V8R 6V5

  • Windsor Regional Cancer Centre

    Windsor, Ontario, N8W 2X3

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

United Kingdom15 sites

  • Sandwell and West Birmingham Hospitals NHS Trust

    Birmingham, B187QH

  • Brighton and Sussex University Hospitals NHS Trust

    Brighton, East Sussex, BN2 5BE

  • North Bristol NHS Trust

    Bristol, Southmead, BS10 5NB

  • Velindre Cancer Centre

    Cardiff, Whitchurch, CF14 2TL

  • Ninewells Hospital

    Dundee, University of Dundee, DD1 9SY

  • University Hospital Birmingham NHS Foundation Trust

    Edgbaston, Birmingham, B15-2WB

  • Edinburgh Cancer Centre, Western General Hospital

    Edinburgh, Crewe Road South, EH4 2XU

  • Medway NHS Foundation Trust

    Gillingham, Kent, ME75NY

  • Withybush General Hospital

    Haverfordwest, Pembrokeshire, SA61 2PZ

  • St George's Healthcare NHS Trust

    London, Tooting, SW17 0QT

  • Kent Centre for Oncology

    Maidstone, Kent, ME16 9QQ

  • The Christie NHS Foundation Trust

    Manchester, Withington, M20-4BX

  • South Tees Hospitals NHS Foundation Trust

    Middlesbrough, Marton Road, TS4 3BW

  • East and North Hertfordshire NHS Trust

    Middlesex, Rickmansworth Road, HA6 2RN

  • Singleton Hospital

    Swansea, Sketty Lane, SA2 8QA

Other trials in United Kingdom

Switzerland8 sites

  • Switzerland-Chur (Ratisches Kantons- und Regionalspital)

    Chur, 7000

  • Brustzentrum Thurgau, Spital Thurgau AG

    Frauenfeld, 8501

  • Fondazione Oncologia Lago Maggiore, FOLM

    Locarno, 6600

  • Switzerland-Luzern (Kantonsspital Luzern)

    Lucerne, 6000

  • Switzerland - Oncology Institute of Southern Switzerland (IOSI)

    Mendrisio, 6850

  • Switzerland - Olten (Kantonsspital) affiliate-3101

    Olten, 4600

  • Switzerland - ZeTup St.Gallen

    Sankt Gallen, 9006

  • Switzerland - Brust-Zentrum, Zurich

    Zurich, 8005

Other trials in Switzerland

About this study

Official title: A Phase III Randomized Trial of Metformin Versus Placebo on Recurrence and Survival in Early Stage Breast Cancer

This study is looking at whether Metformin, an agent that is commonly used to treat diabetes, can decrease or affect the ability of breast cancer cells to grow and whether Metformin will work with other therapies to keep cancer from recurring. Health Canada has not approved the sale or use of Metformin to treat breast cancer, although they have approved its use in this clinical trial. Although Metformin is approved by the FDA for the treatment of diabetes, its use in breast cancer is considered investigational.

Read the detailed description

This is a multicenter study. Patients are stratified according to hormone-receptor status (estrogen receptor- and/or progesterone receptor- positive vs both receptors negative), body mass index (≤ 30 vs > 30 kg/m²), HER2 status (positive vs negative), and prior chemotherapy (any vs none). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral metformin hydrochloride twice daily (once daily in weeks 1-4). Treatment continues for up to 5 years in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive oral placebo twice daily (once daily in weeks 1-4). Treatment continues for up to 5 years in the absence of disease progression or unacceptable toxicity.

Blood and tumor samples are collected periodically for correlative studies.

Patients may complete quality-of-life, physical activity, and diet questionnaires at baseline and at 6, 12, 24, 36, 48, and 60 months. (Sub-set of patients).

After completion of study treatment, patients are followed annually.

Conditions
Breast Cancer
Being tested
metformin hydrochloride, placebo
Keywords
stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIC breast cancer, male breast cancer, HER2-negative breast cancer, estrogen receptor-positive breast cancer, HER2-positive breast cancer, progesterone receptor-positive breast cancer
Medical subject headings
Breast Neoplasms, Breast Neoplasms, Male

What participants receive

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

  • metformin hydrochlorideDrug

    Given orally

  • placeboOther

    Given orally

Study groups in NCT01101438
Study groupRoleWhat they receive
Arm IExperimentalPatients receive oral metformin hydrochloride twice daily (once daily in weeks 1-4). Treatment continues for up to 5 years in receptor positive (ER and/or PgR positive) subjects in the absence of disease progression or unacceptable toxicity.
Receives: Drug: metformin hydrochloride
Arm IIPlacebo comparatorPatients receive oral placebo twice daily (once daily in weeks 1-4). Treatment continues for up to 5 years in receptor positive (ER and/or PgR positive) subjects in the absence of disease progression or unacceptable toxicity.
Receives: Other: placebo

What is being measured

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

  1. Invasive Disease-free Survival in Hormone Receptor (ER and PgR) Positive Sub-groups

    Invasive disease-free survival (IDFS) is defined as percentage of patients without documented development of ipsilateral and contralateral invasive breast tumour, local/regional invasive recurrence, distant recurrence, death from any causes. If a subject has not had invasive disease or died at the time of data cut-off for this final analysis, IDFS was censored on the date of last follow-up.

    Measured: 5 years

  2. Invasive Disease-free Survival

    Invasive disease-free survival (IDFS) is defined as the percent of patients without documented development of ipsilateral and contralateral invasive breast tumour, local/regional invasive recurrence, distant recurrence, death from any causes. If a subject has not had invasive disease or died at the time of data cut-off for this final analysis, IDFS was censored on the date of last follow-up.

    Measured: 5 years

Secondary outcomes (3)

  1. Overall Survival

    Number of patients who died from any causes.

    Measured: 10 years

  2. Distant Relapse-free Survival

    Distant Relapse Free Survival (DRFS) is defined as the percentage of patients without any documented distant recurrence, death from breast cancer, death from a non breast cancer cause or death from an unknown cause. If a subject has not had distant DRFS event nor died at the time of data cut-off for this analysis, DRFS will be censored on the date of last disease assessment.

    Measured: 5 years

  3. Breast Cancer-specific Mortality

    Patients who died from breast cancer

    Measured: 10 years

Timeline

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

  1. First posted12 Apr 2010 (estimated)
  2. Study start13 Aug 2010
  3. Primary completion21 Sep 2021
  4. Study completion18 Aug 2023

Resources

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
3,649 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01101438
Sponsor's protocol ID
MA32
Other IDs
U10CA077202, CAN-NCIC-MA.32, CDR0000669788
Status last verified
Aug 2023
First submitted
9 Apr 2010
Last updated
13 Sep 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Goodwin PJ, Parulekar WR, Gelmon KA, Shepherd LE, Ligibel JA, Hershman DL, Rastogi P, Mayer IA, Hobday TJ, Lemieux J, Thompson AM, Pritchard KI, Whelan TJ, Mukherjee SD, Chalchal HI, Oja CD, Tonkin KS, Bernstein V, Chen BE, Stambolic V. Effect of metformin vs placebo on and metabolic factors in NCIC CTG MA.32. J Natl Cancer Inst. 2015 Mar 4;107(3):djv006. doi: 10.1093/jnci/djv006. Print 2015 Mar.

    PubMed 25740979

  • Goodwin PJ, Chen BE, Gelmon KA, Whelan TJ, Ennis M, Lemieux J, Ligibel JA, Hershman DL, Mayer IA, Hobday TJ, Bliss JM, Rastogi P, Rabaglio-Poretti M, Mukherjee SD, Mackey JR, Abramson VG, Oja C, Wesolowski R, Thompson AM, Rea DW, Stos PM, Shepherd LE, Stambolic V, Parulekar WR. Effect of Metformin vs Placebo on Invasive Disease-Free Survival in Patients With Breast Cancer: The MA.32 Randomized Clinical Trial. JAMA. 2022 May 24;327(20):1963-1973. doi: 10.1001/jama.2022.6147.

    PubMed 35608580

  • Goodwin PJ, Chen BE, Gelmon KA, Whelan TJ, Ennis M, Ligibel J, Stos PM, Shepherd LE, Parulekar WR, Stambolic V. Association of cancer antigen 15-3 with distant recurrence in immunohistochemically defined breast cancer subtypes in Canadian Cancer Trials Group MA.32. JNCI Cancer Spectr. 2026 Jun 25:pkag068. doi: 10.1093/jncics/pkag068. Online ahead of print.

    PubMed 42360727

  • Liao L, Wang G, Li Y, Zou D, Liu J, Ma B, Ma J, Li Y, Qi Y, Ma J, Chen H. Nine-Year Recurrence-Free Survival in Gastric Signet-Ring Cell Carcinoma: A Case Report of Laparoscopic Radical Resection Combining Long-Term Systematic Therapy and Metformin Enteric-Coated Tablets. Case Rep Med. 2026 May 13;2026:6766219. doi: 10.1155/carm/6766219. eCollection 2026.

    PubMed 42137612

  • Goodwin PJ, Ennis M, Chen BE, Gelmon KA, Whelan TJ, Ligibel JA, Thompson AM, Shepherd LE, Parulekar WR, Dowling R, Stambolic V. Exploration of body mass index and circulating metabolic factors as predictors of metformin benefit in the Canadian Cancer Trials Group MA.32. JNCI Cancer Spectr. 2026 Jul 7;10(4):pkag045. doi: 10.1093/jncics/pkag045.

    PubMed 42063220

  • Goodwin PJ, Chen BE, Gelmon KA, Whelan TJ, Ennis M, Lemieux J, Ligibel JA, Hershman DL, Mayer IA, Hobday TJ, Bliss JM, Rastogi P, Rabaglio-Poretti M, Thompson AM, Rea DW, Stos PM, Shepherd LE, Stambolic V, Parulekar WR. Effect of Metformin Versus Placebo on New Primary Cancers in Canadian Cancer Trials Group MA.32: A Secondary Analysis of a Phase III Randomized Double-Blind Trial in Early Breast Cancer. J Clin Oncol. 2023 Dec 10;41(35):5356-5362. doi: 10.1200/JCO.23.00296. Epub 2023 Sep 11.

    PubMed 37695982

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing metformin hydrochloride in people with Breast Cancer, run by Canadian Cancer Trials Group at 344 sites in 4 countries.

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

Who may be eligible to take part?

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 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 344 sites in United States, Canada, United Kingdom, Switzerland. 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 18 Oct 2022). 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?

Invasive Disease-free Survival in Hormone Receptor (ER and PgR) Positive Sub-groups (time frame: 5 years). 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 NCT01101438, which also lists 6 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 13 Sep 2023.

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