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

NCT ID: NCT01101438

Last Updated: 2023-09-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 3649 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-13
• Study Completion Date: 2023-08-18

Brief 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. 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Arm I

Patients 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.

Group Type: EXPERIMENTAL

metformin hydrochloride

Intervention Type: DRUG

Given orally

Arm II

Patients 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.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

Given orally

Interventions

metformin hydrochloride

Given orally

Intervention Type: DRUG

placebo

Given orally

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

ETOP IBCSG Partners Foundation

NETWORK

Sponsor Role: collaborator

Institute of Cancer Research, United Kingdom

OTHER

Sponsor Role: collaborator

Canadian Cancer Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pamela J. Goodwin, MD

Role: PRINCIPAL_INVESTIGATOR

Mount Sinai Hospital, Canada

Locations

Providence Alaska Medical Center

Anchorage, Alaska, United States

Fairbanks Memorial Hospital

Fairbanks, Alaska, United States

Pinnacle Oncology Associates

Scottsdale, Arizona, United States

Mayo Clinic in Arizona

Scottsdale, Arizona, United States

Arizona Cancer Center at University Medical Center North

Tucson, Arizona, United States

University of Arizona Health Sciences Center

Tucson, Arizona, United States

Kaiser Permanente-Deer Valley Medical Center

Antioch, California, United States

Alta Bates Summit Medical Center-Herrick Campus

Berkeley, California, United States

Enloe Medical Center

Chico, California, United States

Glendale Memorial Hospital and Health Center

Glendale, California, United States

Kaiser Permanente, Hayward

Hayward, California, United States

Moores University of California San Diego Cancer Center

La Jolla, California, United States

Long Beach Memorial Medical Center-Todd Cancer Institute

Long Beach, California, United States

University of Southern California

Los Angeles, California, United States

University of California at Los Angeles (UCLA )

Los Angeles, California, United States

Fremont - Rideout Cancer Center

Marysville, California, United States

Bay Area Tumor Institution CCOP

Oakland, California, United States

Kaiser Permanente-Oakland

Oakland, California, United States

University of California Medical Center At Irvine-Orange Campus

Orange, California, United States

Pomona Valley Hospital Medical Center

Pomona, California, United States

Kaiser Permanente-Redwood City

Redwood City, California, United States

Kaiser Permanente-Richmond

Richmond, California, United States

Kaiser Permanente-Roseville

Roseville, California, United States

University of California Davis-Cancer Center

Sacramento, California, United States

Kaiser Permanente-South Sacramento

Sacramento, California, United States

Kaiser Permanente - Sacramento

Sacramento, California, United States

Kaiser Permanente-Mission

San Diego, California, United States

Kaiser Permanente

San Diego, California, United States

Kaiser Permanente-San Francisco

San Francisco, California, United States

University of California San Francisco Medical Center-Mount Zion

San Francisco, California, United States

Kaiser Permanente-Santa Teresa-San Jose

San Jose, California, United States

Kaiser Permanente-San Rafael

San Rafael, California, United States

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California, United States

Kaiser Permanente-Santa Rosa

Santa Rosa, California, United States

Kaiser Permanente-South San Francisco

South San Francisco, California, United States

Stanford University

Stanford, California, United States

Kaiser Permanente-Stockton

Stockton, California, United States

Tahoe Forest Cancer Center

Truckee, California, United States

Kaiser Permanente Medical Center-Vacaville

Vacaville, California, United States

Kaiser Permanente-Vallejo

Vallejo, California, United States

Kaiser Permanente-Walnut Creek

Walnut Creek, California, United States

John Muir Medical Center

Walnut Creek, California, United States

University of Colorado Cancer Center - Anschutz Cancer Pavilion

Aurora, Colorado, United States

Memorial Hospital Colorado Springs

Colorado Springs, Colorado, United States

Kaiser Permanente-Franklin

Denver, Colorado, United States

Poudre Valley Hospital

Fort Collins, Colorado, United States

Front Range Cancer Specialists

Fort Collins, Colorado, United States

University of Connecticut

Farmington, Connecticut, United States

Greenwich Hospital

Greenwich, Connecticut, United States

Hartford Hospital

Hartford, Connecticut, United States

Yale University

New Haven, Connecticut, United States

Stamford Hospital

Stamford, Connecticut, United States

Connecticut Oncology and Hematology LLP

Torrington, Connecticut, United States

Georgetown University Hospital

Washington D.C., District of Columbia, United States

Washington Hospital Center

Washington D.C., District of Columbia, United States

Sibley Memorial Hospital

Washington D.C., District of Columbia, United States

Boca Raton Regional Hospital

Boca Raton, Florida, United States

Mayo Clinic in Florida

Jacksonville, Florida, United States

The Watson Clinic

Lakeland, Florida, United States

Mount Sinai Medical Center CCOP

Miami Beach, Florida, United States

Florida Hospital

Orlando, Florida, United States

Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Phoebe Putney Memorial Hospital

Albany, Georgia, United States

Northeast Georgia Medical Center

Gainesville, Georgia, United States

South Georgia Medical Center

Valdosta, Georgia, United States

University of Hawaii

Honolulu, Hawaii, United States

Kaiser Permanente Moanalua Medical Center

Honolulu, Hawaii, United States

Rush - Copley Medical Center

Aurora, Illinois, United States

Mount Sinai Hospital Medical Center

Chicago, Illinois, United States

John H Stroger Jr Hospital of Cook County

Chicago, Illinois, United States

Swedish Covenant Hospital

Chicago, Illinois, United States

Resurrection Healthcare

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

Decatur Memorial Hospital

Decatur, Illinois, United States

Elmhurst Memorial Hospital

Elmhurst, Illinois, United States

Evanston CCOP-NorthShore University HealthSystem

Evanston, Illinois, United States

Saint Francis Hospital

Evanston, Illinois, United States

Ingalls Memorial Hospital

Harvey, Illinois, United States

Loyola University Medical Center

Maywood, Illinois, United States

Trinity Medical Center

Moline, Illinois, United States

Illinois CancerCare-Peoria

Peoria, Illinois, United States

Illinois Oncology Research Association CCOP

Peoria, Illinois, United States

Memorial Medical Center

Springfield, Illinois, United States

Carle Foundation - Carle Cancer Center

Urbana, Illinois, United States

Elkhart Clinic

Elkhart, Indiana, United States

Michiana Hematology Oncology PC-Elkhart

Elkhart, Indiana, United States

Indiana University Hospital/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Howard Regional Healthcare System

Kokomo, Indiana, United States

Saint Anthony Memorial Health Center

Michigan City, Indiana, United States

Michiana Hematology Oncology PC-Mishawaka

Mishawaka, Indiana, United States

Michiana Hematology Oncology PC-Plymouth

Plymouth, Indiana, United States

Michiana Hematology Oncology PC-South Bend

South Bend, Indiana, United States

Michiana Hematology Oncology-PC Westville

Westville, Indiana, United States

McFarland Clinic

Ames, Iowa, United States

Oncology Associates at Mercy Medical Center

Cedar Rapids, Iowa, United States

Heartland Oncology and Hematology LLP

Council Bluffs, Iowa, United States

Ottumwa Regional Health Center

Ottumwa, Iowa, United States

Siouxland Hematology Oncology Associates

Sioux City, Iowa, United States

Kansas City CCOP

Prairie Village, Kansas, United States

Wichita CCOP

Wichita, Kansas, United States

Central Baptist Hospital

Lexington, Kentucky, United States

Owensboro Mercy Medical Center

Owensboro, Kentucky, United States

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, United States

Eastern Maine Medical Center

Bangor, Maine, United States

York Hospital

York Village, Maine, United States

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, United States

Mercy Medical Center

Baltimore, Maryland, United States

Johns Hopkins University

Baltimore, Maryland, United States

Suburban Hospital

Bethesda, Maryland, United States

Frederick Memorial Hospital

Frederick, Maryland, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Lahey Clinic Medical Center

Burlington, Massachusetts, United States

Addison Gilbert Hospital

Gloucester, Massachusetts, United States

Lowell General Hospital

Lowell, Massachusetts, United States

Saint Vincent Hospital - Fallon Clinic

Worcester, Massachusetts, United States

University of Michigan Health System-Cancer Center

Ann Arbor, Michigan, United States

Battle Creek Health System

Battle Creek, Michigan, United States

Wayne State University

Detroit, Michigan, United States

Grand Rapids Clinical Oncology Program

Grand Rapids, Michigan, United States

Saint Mary's Health Care

Grand Rapids, Michigan, United States

Spectrum Health at Butterworth Campus

Grand Rapids, Michigan, United States

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Mercy Health Partners-Mercy Campus

Muskegon, Michigan, United States

Michiana Hematology Oncology PC-Niles

Niles, Michigan, United States

William Beaumont Hospital

Royal Oak, Michigan, United States

Marie Yeager Cancer Center

Saint Joseph, Michigan, United States

Munson Medical Center

Traverse City, Michigan, United States

Metro Health Hospital

Wyoming, Michigan, United States

Mercy Hospital

Coon Rapids, Minnesota, United States

Duluth Clinic CCOP

Duluth, Minnesota, United States

Fairview-Southdale Hospital

Edina, Minnesota, United States

Unity Hospital

Fridley, Minnesota, United States

Minnesota Oncology Hematology PA-Maplewood

Maplewood, Minnesota, United States

Saint John's Hospital - Healtheast

Maplewood, Minnesota, United States

Abbott-Northwestern Hospital

Minneapolis, Minnesota, United States

North Memorial Medical Health Center

Robbinsdale, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

CentraCare Clinic

Saint Cloud, Minnesota, United States

Metro-Minnesota CCOP

Saint Louis Park, Minnesota, United States

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, Minnesota, United States

Regions Hospital

Saint Paul, Minnesota, United States

United Hospital

Saint Paul, Minnesota, United States

Rice Memorial Hospital

Willmar, Minnesota, United States

Minnesota Oncology and Hematology PA-Woodbury

Woodbury, Minnesota, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Singing River Hospital

Pascagoula, Mississippi, United States

Saint Luke's Hospital

Chesterfield, Missouri, United States

Saint John's Hospital

Springfield, Missouri, United States

Cox Medical Center

Springfield, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Missouri Baptist Medical Center

St Louis, Missouri, United States

Saint John's Mercy Medical Center

St Louis, Missouri, United States

Saint Louis-Cape Girardeau CCOP

St Louis, Missouri, United States

Good Samaritan Hospital

Kearney, Nebraska, United States

Lincoln Medical Education Foundation Cancer Resource Center

Lincoln, Nebraska, United States

Missouri Valley Cancer Consortium CCOP

Omaha, Nebraska, United States

Methodist Estabrook Cancer Center

Omaha, Nebraska, United States

New Hampshire Oncology-Hematology PA

Concord, New Hampshire, United States

New Hampshire Oncology Hematology Associates

Hooksett, New Hampshire, United States

LRGHealthcare-Lakes Region General Hospital

Laconia, New Hampshire, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

The Dana-Farber Cancer Institute at Londonderry

Londonderry, New Hampshire, United States

Saint Barnabas Medical Center

Livingston, New Jersey, United States

Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County

Mount Holly, New Jersey, United States

Valley Hospital

Ridgewood, New Jersey, United States

University of New Mexico

Albuquerque, New Mexico, United States

Presbyterian Kaseman Hospital

Albuquerque, New Mexico, United States

State University of New York Downstate Medical Center

Brooklyn, New York, United States

Maimonides Medical Center

Brooklyn, New York, United States

Coney Island Hospital

Brooklyn, New York, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Hematology Oncology Associates of Central New York PC

East Syracuse, New York, United States

Monter Cancer Center

Lake Success, New York, United States

North Shore University Hospital CCOP

Manhasset, New York, United States

North Shore University Hospital

Manhasset, New York, United States

Mount Kisco Medical Group at Northern Westchester Hospital

Mount Kisco, New York, United States

Mount Kisco Medical Group

Mount Kisco, New York, United States

Long Island Jewish Medical Center

New Hyde Park, New York, United States

Beth Israel Medical Center

New York, New York, United States

New York University Langone Medical Center

New York, New York, United States

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

New York, New York, United States

Mount Sinai Medical Center

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Rochester General Hospital

Rochester, New York, United States

Stony Brook University Medical Center

Stony Brook, New York, United States

State University of New York Upstate Medical University

Syracuse, New York, United States

Albert Einstein College of Medicine

The Bronx, New York, United States

The North Division of Montefiore Medical Center

The Bronx, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Mission Hospitals Inc

Asheville, North Carolina, United States

Presbyterian Hospital

Charlotte, North Carolina, United States

Wayne Memorial Hospital

Goldsboro, North Carolina, United States

Margaret R Pardee Memorial Hospital

Hendersonville, North Carolina, United States

High Point Regional Hospital

High Point, North Carolina, United States

Kinston Medical Specialists PA

Kinston, North Carolina, United States

FirstHealth of the Carolinas-Moore Regional Hosiptal

Pinehurst, North Carolina, United States

Rex Cancer Center

Raleigh, North Carolina, United States

Forsyth Memorial Hospital

Winston-Salem, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Medcenter One Health Systems

Bismarck, North Dakota, United States

Mid Dakota Clinic

Bismarck, North Dakota, United States

Sanford Clinic North-Fargo

Fargo, North Dakota, United States

Sanford Medical Center-Fargo

Fargo, North Dakota, United States

Altru Cancer Center

Grand Forks, North Dakota, United States

Trinity Cancer Care Center

Minot, North Dakota, United States

Akron City Hospital

Akron, Ohio, United States

Akron General Medical Center

Akron, Ohio, United States

Aultman Health Foundation

Canton, Ohio, United States

Case Western Reserve University

Cleveland, Ohio, United States

MetroHealth Medical Center

Cleveland, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Ohio State University Medical Center

Columbus, Ohio, United States

Kettering Medical Center

Kettering, Ohio, United States

Legacy Good Samaritan Hospital and Medical Center

Portland, Oregon, United States

Columbia River Oncology Program

Portland, Oregon, United States

Kaiser Permanente

Portland, Oregon, United States

Oregon Health and Science University

Portland, Oregon, United States

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, United States

Geisinger Medical Center

Danville, Pennsylvania, United States

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

Lancaster General Hospital

Lancaster, Pennsylvania, United States

Paoli Memorial Hospital

Paoli, Pennsylvania, United States

Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Albert Einstein Medical Center

Philadelphia, Pennsylvania, United States

Phoenixville Hospital

Phoenixville, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Saint Joseph Medical Center

Reading, Pennsylvania, United States

Mount Nittany Medical Center

State College, Pennsylvania, United States

Chester County Hospital

West Chester, Pennsylvania, United States

Lankenau Hospital

Wynnewood, Pennsylvania, United States

Memorial Hospital of Rhode Island

Pawtucket, Rhode Island, United States

Rhode Island Hospital

Providence, Rhode Island, United States

Women and Infants Hospital

Providence, Rhode Island, United States

AnMed Health Cancer Center

Anderson, South Carolina, United States

Medical University of South Carolina

Charleston, South Carolina, United States

McLeod Regional Medical Center

Florence, South Carolina, United States

Spartanburg Regional Medical Center

Spartanburg, South Carolina, United States

Rapid City Regional Hospital

Rapid City, South Dakota, United States

Sanford Clinic

Sioux Falls, South Dakota, United States

Avera Cancer Institute

Sioux Falls, South Dakota, United States

University of Tennessee - Knoxville

Knoxville, Tennessee, United States

Vanderbilt Breast Center at One Hundred Oaks

Nashville, Tennessee, United States

Vanderbilt University

Nashville, Tennessee, United States

University Medical Center Brackenridge

Austin, Texas, United States

Doctor's Hospital of Laredo

Laredo, Texas, United States

University of Texas Health Science Center

San Antonio, Texas, United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Mountainview Medical

Berlin Corners, Vermont, United States

University of Vermont

Burlington, Vermont, United States

Martha Jefferson Hospital

Charlottesville, Virginia, United States

Lynchburg Hematology-Oncology Clinic

Lynchburg, Virginia, United States

Saint John Medical Center

Longview, Washington, United States

Virginia Mason CCOP

Seattle, Washington, United States

Pacific Medical Center-First Hill

Seattle, Washington, United States

Group Health Cooperative

Seattle, Washington, United States

Swedish Medical Center-First Hill

Seattle, Washington, United States

University of Washington Medical Center

Seattle, Washington, United States

Rockwood Clinic

Spokane, Washington, United States

Northwest CCOP

Tacoma, Washington, United States

Providence Saint Mary Regional Cancer Center

Walla Walla, Washington, United States

Wenatchee Valley Medical Center

Wenatchee, Washington, United States

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital

Yakima, Washington, United States

Edwards Comprehensive Cancer Center

Huntington, West Virginia, United States

West Virginia University

Morgantown, West Virginia, United States

Wheeling Hospital

Wheeling, West Virginia, United States

Marshfield Clinic Cancer Care at Regional Cancer Center

Eau Claire, Wisconsin, United States

Central Wisconsin Cancer Program

Fond du Lac, Wisconsin, United States

Saint Vincent Hospital

Green Bay, Wisconsin, United States

Aurora BayCare Medical Center

Green Bay, Wisconsin, United States

Gundersen Lutheran Health System/CCOP

La Crosse, Wisconsin, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Marshfield Clinic

Marshfield, Wisconsin, United States

Columbia Saint Mary's Hospital - Ozaukee

Mequon, Wisconsin, United States

Wheaton Franciscan Healthcare - Saint Joseph

Milwaukee, Wisconsin, United States

Columbia Saint Mary's Water Tower Medical Commons

Milwaukee, Wisconsin, United States

Marshfield Clinic-Minocqua Center

Minocqua, Wisconsin, United States

Aurora Medical Center in Summit

Summit, Wisconsin, United States

Marshfield Clinic - Weston Center

Weston, Wisconsin, United States

Cross Cancer Institute

Edmonton, Alberta, Canada

BCCA - Abbotsford Centre

Abbotsford, British Columbia, Canada

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, Canada

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, Canada

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

BCCA - Vancouver Island Cancer Centre

Victoria, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

The Moncton Hospital

Moncton, New Brunswick, Canada

The Vitalite Health Network - Dr. Leon Richard

Moncton, New Brunswick, Canada

Atlantic Health Sciences Corporation

Saint John, New Brunswick, Canada

Dr. H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, Canada

Cambridge Memorial Hospital

Cambridge, Ontario, Canada

Northeast Cancer Center Health Sciences

Greater Sudbury, Ontario, Canada

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, Canada

Grand River Regional Cancer Centre

Kitchener, Ontario, Canada

London Regional Cancer Program

London, Ontario, Canada

Credit Valley Hospital

Mississauga, Ontario, Canada

Stronach Regional Health Centre at Southlake

Newmarket, Ontario, Canada

Lakeridge Health Oshawa

Oshawa, Ontario, Canada

Ottawa Health Research Institute - General Division

Ottawa, Ontario, Canada

Algoma District Cancer Program

Sault Ste. Marie, Ontario, Canada

Niagara Health System

St. Catharines, Ontario, Canada

Thunder Bay Regional Health Science Centre

Thunder Bay, Ontario, Canada

Toronto East General Hospital

Toronto, Ontario, Canada

Odette Cancer Centre

Toronto, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Mount Sinai Hospital

Toronto, Ontario, Canada

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

Trillium Health Centre - West Toronto

Toronto, Ontario, Canada

Windsor Regional Cancer Centre

Windsor, Ontario, Canada

PEI Cancer Treatment Centre,Queen Elizabeth Hospital

Charlottetown, Prince Edward Island, Canada

Hopital Charles LeMoyne

Greenfield Park, Quebec, Canada

Hopital de la Cite-de-la-Sante

Laval, Quebec, Canada

Hopital Maisonneuve-Rosemont

Montreal, Quebec, Canada

McGill University - Dept. Oncology

Montreal, Quebec, Canada

CHUM - Hotel Dieu du Montreal

Montreal, Quebec, Canada

CHUQ-Pavillon Hotel-Dieu de Quebec

Québec, Quebec, Canada

CHA-Hopital Du St-Sacrement

Québec, Quebec, Canada

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

Switzerland-Chur (Ratisches Kantons- und Regionalspital)

Chur, , Switzerland

Brustzentrum Thurgau, Spital Thurgau AG

Frauenfeld, , Switzerland

Fondazione Oncologia Lago Maggiore, FOLM

Locarno, , Switzerland

Switzerland-Luzern (Kantonsspital Luzern)

Lucerne, , Switzerland

Switzerland - Oncology Institute of Southern Switzerland (IOSI)

Mendrisio, , Switzerland

Switzerland - Olten (Kantonsspital) affiliate-3101

Olten, , Switzerland

Switzerland - ZeTup St.Gallen

Sankt Gallen, , Switzerland

Switzerland - Brust-Zentrum, Zurich

Zurich, , Switzerland

University Hospital Birmingham NHS Foundation Trust

Edgbaston, Birmingham, United Kingdom

Edinburgh Cancer Centre, Western General Hospital

Edinburgh, Crewe Road South, United Kingdom

Brighton and Sussex University Hospitals NHS Trust

Brighton, East Sussex, United Kingdom

Medway NHS Foundation Trust

Gillingham, Kent, United Kingdom

Kent Centre for Oncology

Maidstone, Kent, United Kingdom

South Tees Hospitals NHS Foundation Trust

Middlesbrough, Marton Road, United Kingdom

Withybush General Hospital

Haverfordwest, Pembrokeshire, United Kingdom

East and North Hertfordshire NHS Trust

Middlesex, Rickmansworth Road, United Kingdom

Singleton Hospital

Swansea, Sketty Lane, United Kingdom

North Bristol NHS Trust

Bristol, Southmead, United Kingdom

St George's Healthcare NHS Trust

London, Tooting, United Kingdom

Ninewells Hospital

Dundee, University of Dundee, United Kingdom

Velindre Cancer Centre

Cardiff, Whitchurch, United Kingdom

The Christie NHS Foundation Trust

Manchester, Withington, United Kingdom

Sandwell and West Birmingham Hospitals NHS Trust

Birmingham, , United Kingdom

Countries

United States; Canada; Switzerland; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 25740979 (View on PubMed)

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.

Reference Type: RESULT

PMID: 35608580 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37695982 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U10CA077202

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CAN-NCIC-MA.32

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000669788

Identifier Type: OTHER

Identifier Source: secondary_id

MA32

Identifier Type: -

Identifier Source: org_study_id