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

NCT01101438 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: MA32U10CA077202CAN-NCIC-MA.32CDR0000669788
• Study Type: interventional
• Target: 3,649
• Locations: 4 countries
• Sites: 344

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.

Conditions

Breast Cancer

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

Outcome Measures

Primary Outcomes (2)

• 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.

  5 years

• 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.

  5 years

Secondary Outcomes (3)

• Overall Survival

  10 years

• Distant Relapse-free Survival

  5 years

• Breast Cancer-specific Mortality

  10 years

Study Arms (2)

Arm I

EXPERIMENTAL

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.

Drug: metformin hydrochloride

Arm II

PLACEBO COMPARATOR

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.

Other: placebo

Interventions

metformin hydrochloride DRUG

Given orally

Arm I

placebo OTHER

Given orally

Arm II

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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).

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• National Cancer Institute (NCI): collaborator
• ETOP IBCSG Partners Foundation: collaborator
• Institute of Cancer Research, United Kingdom: collaborator

Study Sites (344)

Providence Alaska Medical Center

Anchorage, Alaska, 99508, United States

Location

Fairbanks Memorial Hospital

Fairbanks, Alaska, 99701, United States

Location

Pinnacle Oncology Associates

Scottsdale, Arizona, 85258, United States

Location

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Arizona Cancer Center at University Medical Center North

Tucson, Arizona, 85719, United States

Location

University of Arizona Health Sciences Center

Tucson, Arizona, 85724, United States

Location

Kaiser Permanente-Deer Valley Medical Center

Antioch, California, 94531, United States

Location

Alta Bates Summit Medical Center-Herrick Campus

Berkeley, California, 94704, United States

Location

Enloe Medical Center

Chico, California, 95926, United States

Location

Glendale Memorial Hospital and Health Center

Glendale, California, 91204, United States

Location

Kaiser Permanente, Hayward

Hayward, California, 94545, United States

Location

Moores University of California San Diego Cancer Center

La Jolla, California, 92093, United States

Location

Long Beach Memorial Medical Center-Todd Cancer Institute

Long Beach, California, 90806, United States

Location

University of Southern California

Los Angeles, California, 90033-0804, United States

Location

University of California at Los Angeles (UCLA )

Los Angeles, California, 90095, United States

Location

Fremont - Rideout Cancer Center

Marysville, California, 95901, United States

Location

Bay Area Tumor Institution CCOP

Oakland, California, 94609, United States

Location

Kaiser Permanente-Oakland

Oakland, California, 94611, United States

Location

University of California Medical Center At Irvine-Orange Campus

Orange, California, 92868, United States

Location

Pomona Valley Hospital Medical Center

Pomona, California, 91767, United States

Location

Kaiser Permanente-Redwood City

Redwood City, California, 94063, United States

Location

Kaiser Permanente-Richmond

Richmond, California, 94801, United States

Location

Kaiser Permanente-Roseville

Roseville, California, 95661, United States

Location

University of California Davis-Cancer Center

Sacramento, California, 95817, United States

Location

Kaiser Permanente-South Sacramento

Sacramento, California, 95823, United States

Location

Kaiser Permanente - Sacramento

Sacramento, California, 95825, United States

Location

Kaiser Permanente-Mission

San Diego, California, 92108, United States

Location

Kaiser Permanente

San Diego, California, 92108, United States

Location

Kaiser Permanente-San Francisco

San Francisco, California, 94115, United States

Location

University of California San Francisco Medical Center-Mount Zion

San Francisco, California, 94115, United States

Location

Kaiser Permanente-Santa Teresa-San Jose

San Jose, California, 95119, United States

Location

Kaiser Permanente-San Rafael

San Rafael, California, 94903, United States

Location

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California, 95051, United States

Location

Kaiser Permanente-Santa Rosa

Santa Rosa, California, 95403, United States

Location

Kaiser Permanente-South San Francisco

South San Francisco, California, 94080, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Kaiser Permanente-Stockton

Stockton, California, 95210, United States

Location

Tahoe Forest Cancer Center

Truckee, California, 96161, United States

Location

Kaiser Permanente Medical Center-Vacaville

Vacaville, California, 95688, United States

Location

Kaiser Permanente-Vallejo

Vallejo, California, 94589, United States

Location

Kaiser Permanente-Walnut Creek

Walnut Creek, California, 94596, United States

Location

John Muir Medical Center

Walnut Creek, California, 94598, United States

Location

University of Colorado Cancer Center - Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

Memorial Hospital Colorado Springs

Colorado Springs, Colorado, 80909, United States

Location

Kaiser Permanente-Franklin

Denver, Colorado, 80205, United States

Location

Poudre Valley Hospital

Fort Collins, Colorado, 80524, United States

Location

Front Range Cancer Specialists

Fort Collins, Colorado, 80528, United States

Location

University of Connecticut

Farmington, Connecticut, 06030, United States

Location

Greenwich Hospital

Greenwich, Connecticut, 06830, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Yale University

New Haven, Connecticut, 06520-8032, United States

Location

Stamford Hospital

Stamford, Connecticut, 06904, United States

Location

Connecticut Oncology and Hematology LLP

Torrington, Connecticut, 06790, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

Boca Raton Regional Hospital

Boca Raton, Florida, 33486, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

The Watson Clinic

Lakeland, Florida, 33805, United States

Location

Mount Sinai Medical Center CCOP

Miami Beach, Florida, 33140, United States

Location

Florida Hospital

Orlando, Florida, 32803, United States

Location

Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Phoebe Putney Memorial Hospital

Albany, Georgia, 31701, United States

Location

Northeast Georgia Medical Center

Gainesville, Georgia, 30501, United States

Location

South Georgia Medical Center

Valdosta, Georgia, 31602, United States

Location

University of Hawaii

Honolulu, Hawaii, 96813, United States

Location

Kaiser Permanente Moanalua Medical Center

Honolulu, Hawaii, 96819, United States

Location

Rush - Copley Medical Center

Aurora, Illinois, 60504, United States

Location

Mount Sinai Hospital Medical Center

Chicago, Illinois, 60608, United States

Location

John H Stroger Jr Hospital of Cook County

Chicago, Illinois, 60612-3785, United States

Location

Swedish Covenant Hospital

Chicago, Illinois, 60625, United States

Location

Resurrection Healthcare

Chicago, Illinois, 60631, United States

Location

University of Chicago

Chicago, Illinois, 60637-1470, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

Elmhurst Memorial Hospital

Elmhurst, Illinois, 60126, United States

Location

Evanston CCOP-NorthShore University HealthSystem

Evanston, Illinois, 60201, United States

Location

Saint Francis Hospital

Evanston, Illinois, 60202, United States

Location

Ingalls Memorial Hospital

Harvey, Illinois, 60426, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Trinity Medical Center

Moline, Illinois, 61265, United States

Location

Illinois CancerCare-Peoria

Peoria, Illinois, 61615, United States

Location

Illinois Oncology Research Association CCOP

Peoria, Illinois, 61615, United States

Location

Memorial Medical Center

Springfield, Illinois, 62781-0001, United States

Location

Carle Foundation - Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

Elkhart Clinic

Elkhart, Indiana, 46514-2098, United States

Location

Michiana Hematology Oncology PC-Elkhart

Elkhart, Indiana, 46514, United States

Location

Indiana University Hospital/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Howard Regional Healthcare System

Kokomo, Indiana, 46904, United States

Location

Saint Anthony Memorial Health Center

Michigan City, Indiana, 46360, United States

Location

Michiana Hematology Oncology PC-Mishawaka

Mishawaka, Indiana, 46545-1470, United States

Location

Michiana Hematology Oncology PC-Plymouth

Plymouth, Indiana, 46563, United States

Location

Michiana Hematology Oncology PC-South Bend

South Bend, Indiana, 46601, United States

Location

Michiana Hematology Oncology-PC Westville

Westville, Indiana, 46391, United States

Location

McFarland Clinic

Ames, Iowa, 50010, United States

Location

Oncology Associates at Mercy Medical Center

Cedar Rapids, Iowa, 52403, United States

Location

Heartland Oncology and Hematology LLP

Council Bluffs, Iowa, 51503, United States

Location

Ottumwa Regional Health Center

Ottumwa, Iowa, 52501, United States

Location

Siouxland Hematology Oncology Associates

Sioux City, Iowa, 51101, United States

Location

Kansas City CCOP

Prairie Village, Kansas, 66208, United States

Location

Wichita CCOP

Wichita, Kansas, 67214, United States

Location

Central Baptist Hospital

Lexington, Kentucky, 40503, United States

Location

Owensboro Mercy Medical Center

Owensboro, Kentucky, 42303, United States

Location

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, 70809, United States

Location

Eastern Maine Medical Center

Bangor, Maine, 04401, United States

Location

York Hospital

York Village, Maine, 03909, United States

Location

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201-1595, United States

Location

Mercy Medical Center

Baltimore, Maryland, 21202, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287-8936, United States

Location

Suburban Hospital

Bethesda, Maryland, 20814, United States

Location

Frederick Memorial Hospital

Frederick, Maryland, 21701, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Lahey Clinic Medical Center

Burlington, Massachusetts, 01805, United States

Location

Addison Gilbert Hospital

Gloucester, Massachusetts, 01930, United States

Location

Lowell General Hospital

Lowell, Massachusetts, 01854, United States

Location

Saint Vincent Hospital - Fallon Clinic

Worcester, Massachusetts, 01608, United States

Location

University of Michigan Health System-Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Battle Creek Health System

Battle Creek, Michigan, 49017, United States

Location

Wayne State University

Detroit, Michigan, 48202, United States

Location

Grand Rapids Clinical Oncology Program

Grand Rapids, Michigan, 49503, United States

Location

Saint Mary's Health Care

Grand Rapids, Michigan, 49503, United States

Location

Spectrum Health at Butterworth Campus

Grand Rapids, Michigan, 49503, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007, United States

Location

Mercy Health Partners-Mercy Campus

Muskegon, Michigan, 49444, United States

Location

Michiana Hematology Oncology PC-Niles

Niles, Michigan, 49120, United States

Location

William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

Marie Yeager Cancer Center

Saint Joseph, Michigan, 49085, United States

Location

Munson Medical Center

Traverse City, Michigan, 49684, United States

Location

Metro Health Hospital

Wyoming, Michigan, 49519, United States

Location

Mercy Hospital

Coon Rapids, Minnesota, 55433, United States

Location

Duluth Clinic CCOP

Duluth, Minnesota, 55805, United States

Location

Fairview-Southdale Hospital

Edina, Minnesota, 55435, United States

Location

Unity Hospital

Fridley, Minnesota, 55432, United States

Location

Minnesota Oncology Hematology PA-Maplewood

Maplewood, Minnesota, 55109, United States

Location

Saint John's Hospital - Healtheast

Maplewood, Minnesota, 55109, United States

Location

Abbott-Northwestern Hospital

Minneapolis, Minnesota, 55407, United States

Location

North Memorial Medical Health Center

Robbinsdale, Minnesota, 55422, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

CentraCare Clinic

Saint Cloud, Minnesota, 56303, United States

Location

Metro-Minnesota CCOP

Saint Louis Park, Minnesota, 55416, United States

Location

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, Minnesota, 55416, United States

Location

Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

United Hospital

Saint Paul, Minnesota, 55102, United States

Location

Rice Memorial Hospital

Willmar, Minnesota, 56201, United States

Location

Minnesota Oncology and Hematology PA-Woodbury

Woodbury, Minnesota, 55125, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Singing River Hospital

Pascagoula, Mississippi, 39581, United States

Location

Saint Luke's Hospital

Chesterfield, Missouri, 63017, United States

Location

Saint John's Hospital

Springfield, Missouri, 65804, United States

Location

Cox Medical Center

Springfield, Missouri, 65807, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Missouri Baptist Medical Center

St Louis, Missouri, 63131, United States

Location

Saint John's Mercy Medical Center

St Louis, Missouri, 63141, United States

Location

Saint Louis-Cape Girardeau CCOP

St Louis, Missouri, 63141, United States

Location

Good Samaritan Hospital

Kearney, Nebraska, 68847, United States

Location

Lincoln Medical Education Foundation Cancer Resource Center

Lincoln, Nebraska, 68510, United States

Location

Missouri Valley Cancer Consortium CCOP

Omaha, Nebraska, 68106, United States

Location

Methodist Estabrook Cancer Center

Omaha, Nebraska, 68114, United States

Location

New Hampshire Oncology-Hematology PA

Concord, New Hampshire, 03301, United States

Location

New Hampshire Oncology Hematology Associates

Hooksett, New Hampshire, 03106, United States

Location

LRGHealthcare-Lakes Region General Hospital

Laconia, New Hampshire, 03246, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

The Dana-Farber Cancer Institute at Londonderry

Londonderry, New Hampshire, 03053, United States

Location

Saint Barnabas Medical Center

Livingston, New Jersey, 07039, United States

Location

Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County

Mount Holly, New Jersey, 08060, United States

Location

Valley Hospital

Ridgewood, New Jersey, 07450, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87106, United States

Location

Presbyterian Kaseman Hospital

Albuquerque, New Mexico, 87110, United States

Location

State University of New York Downstate Medical Center

Brooklyn, New York, 11203, United States

Location

Maimonides Medical Center

Brooklyn, New York, 11219, United States

Location

Coney Island Hospital

Brooklyn, New York, 11235, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Hematology Oncology Associates of Central New York PC

East Syracuse, New York, 13057, United States

Location

Monter Cancer Center

Lake Success, New York, 11042, United States

Location

North Shore University Hospital CCOP

Manhasset, New York, 11030, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Mount Kisco Medical Group at Northern Westchester Hospital

Mount Kisco, New York, 10549-3417, United States

Location

Mount Kisco Medical Group

Mount Kisco, New York, 10549, United States

Location

Long Island Jewish Medical Center

New Hyde Park, New York, 11040, United States

Location

Beth Israel Medical Center

New York, New York, 10003, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

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

New York, New York, 10025, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Rochester General Hospital

Rochester, New York, 14621, United States

Location

Stony Brook University Medical Center

Stony Brook, New York, 11794, United States

Location

State University of New York Upstate Medical University

Syracuse, New York, 13210, United States

Location

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

The North Division of Montefiore Medical Center

The Bronx, New York, 10466, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467-2490, United States

Location

Mission Hospitals Inc

Asheville, North Carolina, 28801, United States

Location

Presbyterian Hospital

Charlotte, North Carolina, 28204, United States

Location

Wayne Memorial Hospital

Goldsboro, North Carolina, 27534, United States

Location

Margaret R Pardee Memorial Hospital

Hendersonville, North Carolina, 28791, United States

Location

High Point Regional Hospital

High Point, North Carolina, 27261, United States

Location

Kinston Medical Specialists PA

Kinston, North Carolina, 28501, United States

Location

FirstHealth of the Carolinas-Moore Regional Hosiptal

Pinehurst, North Carolina, 28374, United States

Location

Rex Cancer Center

Raleigh, North Carolina, 27607, United States

Location

Forsyth Memorial Hospital

Winston-Salem, North Carolina, 27103, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Medcenter One Health Systems

Bismarck, North Dakota, 58501, United States

Location

Mid Dakota Clinic

Bismarck, North Dakota, 58501, United States

Location

Sanford Clinic North-Fargo

Fargo, North Dakota, 58102, United States

Location

Sanford Medical Center-Fargo

Fargo, North Dakota, 58122, United States

Location

Altru Cancer Center

Grand Forks, North Dakota, 58201, United States

Location

Trinity Cancer Care Center

Minot, North Dakota, 58701, United States

Location

Akron City Hospital

Akron, Ohio, 44304, United States

Location

Akron General Medical Center

Akron, Ohio, 44307, United States

Location

Aultman Health Foundation

Canton, Ohio, 44710, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Kettering Medical Center

Kettering, Ohio, 45429, United States

Location

Legacy Good Samaritan Hospital and Medical Center

Portland, Oregon, 97210, United States

Location

Columbia River Oncology Program

Portland, Oregon, 97225, United States

Location

Kaiser Permanente

Portland, Oregon, 97227, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, 19010, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822-2001, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Lancaster General Hospital

Lancaster, Pennsylvania, 17604, United States

Location

Paoli Memorial Hospital

Paoli, Pennsylvania, 19301, United States

Location

Pennsylvania Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111-2497, United States

Location

Albert Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

Phoenixville Hospital

Phoenixville, Pennsylvania, 19460, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States

Location

Saint Joseph Medical Center

Reading, Pennsylvania, 19605, United States

Location

Mount Nittany Medical Center

State College, Pennsylvania, 16803, United States

Location

Chester County Hospital

West Chester, Pennsylvania, 19380, United States

Location

Lankenau Hospital

Wynnewood, Pennsylvania, 19096, United States

Location

Memorial Hospital of Rhode Island

Pawtucket, Rhode Island, 02860, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Women and Infants Hospital

Providence, Rhode Island, 02905, United States

Location

AnMed Health Cancer Center

Anderson, South Carolina, 29621, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

McLeod Regional Medical Center

Florence, South Carolina, 29506, United States

Location

Spartanburg Regional Medical Center

Spartanburg, South Carolina, 29303, United States

Location

Rapid City Regional Hospital

Rapid City, South Dakota, 57701, United States

Location

Sanford Clinic

Sioux Falls, South Dakota, 57104, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

Location

University of Tennessee - Knoxville

Knoxville, Tennessee, 37920, United States

Location

Vanderbilt Breast Center at One Hundred Oaks

Nashville, Tennessee, 37204, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

University Medical Center Brackenridge

Austin, Texas, 78701, United States

Location

Doctor's Hospital of Laredo

Laredo, Texas, 78045, United States

Location

University of Texas Health Science Center

San Antonio, Texas, 78229-3900, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

Mountainview Medical

Berlin Corners, Vermont, 05602, United States

Location

University of Vermont

Burlington, Vermont, 05401, United States

Location

Martha Jefferson Hospital

Charlottesville, Virginia, 22901, United States

Location

Lynchburg Hematology-Oncology Clinic

Lynchburg, Virginia, 24501, United States

Location

Saint John Medical Center

Longview, Washington, 98632, United States

Location

Virginia Mason CCOP

Seattle, Washington, 98101, United States

Location

Pacific Medical Center-First Hill

Seattle, Washington, 98104, United States

Location

Group Health Cooperative

Seattle, Washington, 98112, United States

Location

Swedish Medical Center-First Hill

Seattle, Washington, 98122-4307, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Rockwood Clinic

Spokane, Washington, 99220, United States

Location

Northwest CCOP

Tacoma, Washington, 98405, United States

Location

Providence Saint Mary Regional Cancer Center

Walla Walla, Washington, 99362, United States

Location

Wenatchee Valley Medical Center

Wenatchee, Washington, 98801, United States

Location

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital

Yakima, Washington, 98902, United States

Location

Edwards Comprehensive Cancer Center

Huntington, West Virginia, 25701, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

Wheeling Hospital

Wheeling, West Virginia, 26003, United States

Location

Marshfield Clinic Cancer Care at Regional Cancer Center

Eau Claire, Wisconsin, 54701, United States

Location

Central Wisconsin Cancer Program

Fond du Lac, Wisconsin, 54935, United States

Location

Saint Vincent Hospital

Green Bay, Wisconsin, 54301, United States

Location

Aurora BayCare Medical Center

Green Bay, Wisconsin, 54311-6519, United States

Location

Gundersen Lutheran Health System/CCOP

La Crosse, Wisconsin, 54601, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Marshfield Clinic

Marshfield, Wisconsin, 54449, United States

Location

Columbia Saint Mary's Hospital - Ozaukee

Mequon, Wisconsin, 53097, United States

Location

Wheaton Franciscan Healthcare - Saint Joseph

Milwaukee, Wisconsin, 53210, United States

Location

Columbia Saint Mary's Water Tower Medical Commons

Milwaukee, Wisconsin, 53211, United States

Location

Marshfield Clinic-Minocqua Center

Minocqua, Wisconsin, 54548, United States

Location

Aurora Medical Center in Summit

Summit, Wisconsin, 53066, United States

Location

Marshfield Clinic - Weston Center

Weston, Wisconsin, 54476, United States

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Abbotsford Centre

Abbotsford, British Columbia, V2S 0C2, Canada

Location

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

BCCA - Vancouver Island Cancer Centre

Victoria, British Columbia, V8R 6V5, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

The Moncton Hospital

Moncton, New Brunswick, E1C 6Z8, Canada

Location

The Vitalite Health Network - Dr. Leon Richard

Moncton, New Brunswick, E1C 8X3, Canada

Location

Atlantic Health Sciences Corporation

Saint John, New Brunswick, E2L 4L2, Canada

Location

Dr. H. Bliss Murphy Cancer Centre

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

Location

Cambridge Memorial Hospital

Cambridge, Ontario, N1R 3G2, Canada

Location

Northeast Cancer Center Health Sciences

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, K7L 5P9, Canada

Location

Grand River Regional Cancer Centre

Kitchener, Ontario, N2G 1G3, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Credit Valley Hospital

Mississauga, Ontario, L5M 2N1, Canada

Location

Stronach Regional Health Centre at Southlake

Newmarket, Ontario, L3Y 2P9, Canada

Location

Lakeridge Health Oshawa

Oshawa, Ontario, L1G 2B9, Canada

Location

Ottawa Health Research Institute - General Division

Ottawa, Ontario, K1H 8L6, Canada

Location

Algoma District Cancer Program

Sault Ste. Marie, Ontario, P6B 0A8, Canada

Location

Niagara Health System

St. Catharines, Ontario, L2R 7C6, Canada

Location

Thunder Bay Regional Health Science Centre

Thunder Bay, Ontario, P7B 6V4, Canada

Location

Toronto East General Hospital

Toronto, Ontario, M4C 3E7, Canada

Location

Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Trillium Health Centre - West Toronto

Toronto, Ontario, M9C 1A5, Canada

Location

Windsor Regional Cancer Centre

Windsor, Ontario, N8W 2X3, Canada

Location

PEI Cancer Treatment Centre,Queen Elizabeth Hospital

Charlottetown, Prince Edward Island, C1A 8T5, Canada

Location

Hopital Charles LeMoyne

Greenfield Park, Quebec, J4V 2H1, Canada

Location

Hopital de la Cite-de-la-Sante

Laval, Quebec, H7M 3L9, Canada

Location

Hopital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

McGill University - Dept. Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

CHUM - Hotel Dieu du Montreal

Montreal, Quebec, H2W 1T8, Canada

Location

CHUQ-Pavillon Hotel-Dieu de Quebec

Québec, Quebec, G1R 2J6, Canada

Location

CHA-Hopital Du St-Sacrement

Québec, Quebec, G1S 4L8, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Switzerland-Chur (Ratisches Kantons- und Regionalspital)

Chur, 7000, Switzerland

Location

Brustzentrum Thurgau, Spital Thurgau AG

Frauenfeld, 8501, Switzerland

Location

Fondazione Oncologia Lago Maggiore, FOLM

Locarno, 6600, Switzerland

Location

Switzerland-Luzern (Kantonsspital Luzern)

Lucerne, 6000, Switzerland

Location

Switzerland - Oncology Institute of Southern Switzerland (IOSI)

Mendrisio, 6850, Switzerland

Location

Switzerland - Olten (Kantonsspital) affiliate-3101

Olten, 4600, Switzerland

Location

Switzerland - ZeTup St.Gallen

Sankt Gallen, 9006, Switzerland

Location

Switzerland - Brust-Zentrum, Zurich

Zurich, 8005, Switzerland

Location

University Hospital Birmingham NHS Foundation Trust

Edgbaston, Birmingham, B15-2WB, United Kingdom

Location

Edinburgh Cancer Centre, Western General Hospital

Edinburgh, Crewe Road South, EH4 2XU, United Kingdom

Location

Brighton and Sussex University Hospitals NHS Trust

Brighton, East Sussex, BN2 5BE, United Kingdom

Location

Medway NHS Foundation Trust

Gillingham, Kent, ME75NY, United Kingdom

Location

Kent Centre for Oncology

Maidstone, Kent, ME16 9QQ, United Kingdom

Location

South Tees Hospitals NHS Foundation Trust

Middlesbrough, Marton Road, TS4 3BW, United Kingdom

Location

Withybush General Hospital

Haverfordwest, Pembrokeshire, SA61 2PZ, United Kingdom

Location

East and North Hertfordshire NHS Trust

Middlesex, Rickmansworth Road, HA6 2RN, United Kingdom

Location

Singleton Hospital

Swansea, Sketty Lane, SA2 8QA, United Kingdom

Location

North Bristol NHS Trust

Bristol, Southmead, BS10 5NB, United Kingdom

Location

St George's Healthcare NHS Trust

London, Tooting, SW17 0QT, United Kingdom

Location

Ninewells Hospital

Dundee, University of Dundee, DD1 9SY, United Kingdom

Location

Velindre Cancer Centre

Cardiff, Whitchurch, CF14 2TL, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, Withington, M20-4BX, United Kingdom

Location

Sandwell and West Birmingham Hospitals NHS Trust

Birmingham, B187QH, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 25740979 BACKGROUND

• 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.

  PMID: 35608580 RESULT

• 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.

  PMID: 37695982 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Breast Neoplasms, Male

Interventions

Metformin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Professor Bingshu Chen
• Organization: Canadian Cancer Trials Group

bechen@ctg.queensu.ca

+16135336000

Study Officials

• Pamela J. Goodwin, MD

  Mount Sinai Hospital, Canada

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2010
• First Posted: April 12, 2010
• Study Start: August 13, 2010
• Primary Completion: September 21, 2021
• Study Completion: August 18, 2023
• Last Updated: September 13, 2023
• Results First Posted: October 18, 2022

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (280); CA (41); CH (8); GB (15)