Clinical trial NCT01101438: A Phase III Randomized Trial of Metformin vs Placebo in Early Stage Breast Cancer
Official title: A Phase III Randomized Trial of Metformin Versus Placebo on Recurrence and Survival in Early Stage Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: ETOP IBCSG Partners Foundation
name: Institute of Cancer Research, United Kingdom
First posted: 2010-04-12
Enrollment: 3649
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Invasive Disease-free Survival in Hormone Receptor (ER and PgR) Positive Sub-groups
timeFrame: 5 years
measure: Invasive Disease-free Survival
timeFrame: 5 years
Secondary outcomes:
measure: Overall Survival
timeFrame: 10 years
measure: Distant Relapse-free Survival
timeFrame: 5 years
measure: Breast Cancer-specific Mortality
timeFrame: 10 years
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Providence Alaska Medical Center
state: Alaska
city: Fairbanks
country: United States
facility: Fairbanks Memorial Hospital
state: Alaska
city: Scottsdale
country: United States
facility: Pinnacle Oncology Associates
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Tucson
country: United States
facility: Arizona Cancer Center at University Medical Center North
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Health Sciences Center
state: Arizona
city: Antioch
country: United States
facility: Kaiser Permanente-Deer Valley Medical Center
state: California
city: Berkeley
country: United States
facility: Alta Bates Summit Medical Center-Herrick Campus
state: California
city: Chico
country: United States
facility: Enloe Medical Center
state: California
city: Glendale
country: United States
facility: Glendale Memorial Hospital and Health Center
state: California
city: Hayward
country: United States
facility: Kaiser Permanente, Hayward
state: California
city: La Jolla
country: United States
facility: Moores University of California San Diego Cancer Center
state: California
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center-Todd Cancer Institute
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: University of California at Los Angeles (UCLA )
state: California
city: Marysville
country: United States
facility: Fremont - Rideout Cancer Center
state: California
city: Oakland
country: United States
facility: Bay Area Tumor Institution CCOP
state: California
city: Oakland
country: United States
facility: Kaiser Permanente-Oakland
state: California
city: Orange
country: United States
facility: University of California Medical Center At Irvine-Orange Campus
state: California
city: Pomona
country: United States
facility: Pomona Valley Hospital Medical Center
state: California
city: Redwood City
country: United States
facility: Kaiser Permanente-Redwood City
state: California
city: Richmond
country: United States
facility: Kaiser Permanente-Richmond
state: California
city: Roseville
country: United States
facility: Kaiser Permanente-Roseville
state: California
city: Sacramento
country: United States
facility: University of California Davis-Cancer Center
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente-South Sacramento
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente - Sacramento
state: California
city: San Diego
country: United States
facility: Kaiser Permanente-Mission
state: California
city: San Diego
country: United States
facility: Kaiser Permanente
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente-San Francisco
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center-Mount Zion
state: California
city: San Jose
country: United States
facility: Kaiser Permanente-Santa Teresa-San Jose
state: California
city: San Rafael
country: United States
facility: Kaiser Permanente-San Rafael
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente Medical Center - Santa Clara
state: California
city: Santa Rosa
country: United States
facility: Kaiser Permanente-Santa Rosa
state: California
city: South San Francisco
country: United States
facility: Kaiser Permanente-South San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Stockton
country: United States
facility: Kaiser Permanente-Stockton
state: California
city: Truckee
country: United States
facility: Tahoe Forest Cancer Center
state: California
city: Vacaville
country: United States
facility: Kaiser Permanente Medical Center-Vacaville
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente-Vallejo
state: California
city: Walnut Creek
country: United States
facility: Kaiser Permanente-Walnut Creek
state: California
city: Walnut Creek
country: United States
facility: John Muir Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center - Anschutz Cancer Pavilion
state: Colorado
city: Colorado Springs
country: United States
facility: Memorial Hospital Colorado Springs
state: Colorado
city: Denver
country: United States
facility: Kaiser Permanente-Franklin
state: Colorado
city: Fort Collins
country: United States
facility: Poudre Valley Hospital
state: Colorado
city: Fort Collins
country: United States
facility: Front Range Cancer Specialists
state: Colorado
city: Farmington
country: United States
facility: University of Connecticut
state: Connecticut
city: Greenwich
country: United States
facility: Greenwich Hospital
state: Connecticut
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Stamford
country: United States
facility: Stamford Hospital
state: Connecticut
city: Torrington
country: United States
facility: Connecticut Oncology and Hematology LLP
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Washington
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Boca Raton
country: United States
facility: Boca Raton Regional Hospital
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Lakeland
country: United States
facility: The Watson Clinic
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center CCOP
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center and Research Institute
state: Florida
city: Albany
country: United States
facility: Phoebe Putney Memorial Hospital
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Valdosta
country: United States
facility: South Georgia Medical Center
state: Georgia
city: Honolulu
country: United States
facility: University of Hawaii
state: Hawaii
city: Honolulu
country: United States
facility: Kaiser Permanente Moanalua Medical Center
state: Hawaii
city: Aurora
country: United States
facility: Rush - Copley Medical Center
state: Illinois
city: Chicago
country: United States
facility: Mount Sinai Hospital Medical Center
state: Illinois
city: Chicago
country: United States
facility: John H Stroger Jr Hospital of Cook County
state: Illinois
city: Chicago
country: United States
facility: Swedish Covenant Hospital
state: Illinois
city: Chicago
country: United States
facility: Resurrection Healthcare
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Elmhurst
country: United States
facility: Elmhurst Memorial Hospital
state: Illinois
city: Evanston
country: United States
facility: Evanston CCOP-NorthShore University HealthSystem
state: Illinois
city: Evanston
country: United States
facility: Saint Francis Hospital
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Moline
country: United States
facility: Trinity Medical Center
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Peoria
country: United States
facility: Illinois Oncology Research Association CCOP
state: Illinois
city: Springfield
country: United States
facility: Memorial Medical Center
state: Illinois
city: Urbana
country: United States
facility: Carle Foundation - Carle Cancer Center
state: Illinois
city: Elkhart
country: United States
facility: Elkhart Clinic
state: Indiana
city: Elkhart
country: United States
facility: Michiana Hematology Oncology PC-Elkhart
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Hospital/Melvin and Bren Simon Cancer Center
state: Indiana
city: Kokomo
country: United States
facility: Howard Regional Healthcare System
state: Indiana
city: Michigan City
country: United States
facility: Saint Anthony Memorial Health Center
state: Indiana
city: Mishawaka
country: United States
facility: Michiana Hematology Oncology PC-Mishawaka
state: Indiana
city: Plymouth
country: United States
facility: Michiana Hematology Oncology PC-Plymouth
state: Indiana
city: South Bend
country: United States
facility: Michiana Hematology Oncology PC-South Bend
state: Indiana
city: Westville
country: United States
facility: Michiana Hematology Oncology-PC Westville
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic
state: Iowa
city: Cedar Rapids
country: United States
facility: Oncology Associates at Mercy Medical Center
state: Iowa
city: Council Bluffs
country: United States
facility: Heartland Oncology and Hematology LLP
state: Iowa
city: Ottumwa
country: United States
facility: Ottumwa Regional Health Center
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology Oncology Associates
state: Iowa
city: Prairie Village
country: United States
facility: Kansas City CCOP
state: Kansas
city: Wichita
country: United States
facility: Wichita CCOP
state: Kansas
city: Lexington
country: United States
facility: Central Baptist Hospital
state: Kentucky
city: Owensboro
country: United States
facility: Owensboro Mercy Medical Center
state: Kentucky
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center
state: Louisiana
city: Bangor
country: United States
facility: Eastern Maine Medical Center
state: Maine
city: York
country: United States
facility: York Hospital
state: Maine
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Bethesda
country: United States
facility: Suburban Hospital
state: Maryland
city: Frederick
country: United States
facility: Frederick Memorial Hospital
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Clinic Medical Center
state: Massachusetts
city: Gloucester
country: United States
facility: Addison Gilbert Hospital
state: Massachusetts
city: Lowell
country: United States
facility: Lowell General Hospital
state: Massachusetts
city: Worcester
country: United States
facility: Saint Vincent Hospital - Fallon Clinic
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System-Cancer Center
state: Michigan
city: Battle Creek
country: United States
facility: Battle Creek Health System
state: Michigan
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Grand Rapids
country: United States
facility: Grand Rapids Clinical Oncology Program
state: Michigan
city: Grand Rapids
country: United States
facility: Saint Mary's Health Care
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health at Butterworth Campus
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Muskegon
country: United States
facility: Mercy Health Partners-Mercy Campus
state: Michigan
city: Niles
country: United States
facility: Michiana Hematology Oncology PC-Niles
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Saint Joseph
country: United States
facility: Marie Yeager Cancer Center
state: Michigan
city: Traverse City
country: United States
facility: Munson Medical Center
state: Michigan
city: Wyoming
country: United States
facility: Metro Health Hospital
state: Michigan
city: Coon Rapids
country: United States
facility: Mercy Hospital
state: Minnesota
city: Duluth
country: United States
facility: Duluth Clinic CCOP
state: Minnesota
city: Edina
country: United States
facility: Fairview-Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Unity Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology Hematology PA-Maplewood
state: Minnesota
city: Maplewood
country: United States
facility: Saint John's Hospital - Healtheast
state: Minnesota
city: Minneapolis
country: United States
facility: Abbott-Northwestern Hospital
state: Minnesota
city: Robbinsdale
country: United States
facility: North Memorial Medical Health Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Cloud
country: United States
facility: CentraCare Clinic
state: Minnesota
city: Saint Louis Park
country: United States
facility: Metro-Minnesota CCOP
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Clinic - Saint Louis Park
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Willmar
country: United States
facility: Rice Memorial Hospital
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology and Hematology PA-Woodbury
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Pascagoula
country: United States
facility: Singing River Hospital
state: Mississippi
city: Chesterfield
country: United States
facility: Saint Luke's Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Saint John's Mercy Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis-Cape Girardeau CCOP
state: Missouri
city: Springfield
country: United States
facility: Saint John's Hospital
state: Missouri
city: Springfield
country: United States
facility: Cox Medical Center
state: Missouri
city: Kearney
country: United States
facility: Good Samaritan Hospital
state: Nebraska
city: Lincoln
country: United States
facility: Lincoln Medical Education Foundation Cancer Resource Center
state: Nebraska
city: Omaha
country: United States
facility: Missouri Valley Cancer Consortium CCOP
state: Nebraska
city: Omaha
country: United States
facility: Methodist Estabrook Cancer Center
state: Nebraska
city: Concord
country: United States
facility: New Hampshire Oncology-Hematology PA
state: New Hampshire
city: Hooksett
country: United States
facility: New Hampshire Oncology Hematology Associates
state: New Hampshire
city: Laconia
country: United States
facility: LRGHealthcare-Lakes Region General Hospital
state: New Hampshire
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Londonderry
country: United States
facility: The Dana-Farber Cancer Institute at Londonderry
state: New Hampshire
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: Mount Holly
country: United States
facility: Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
state: New Jersey
city: Ridgewood
country: United States
facility: Valley Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Albuquerque
country: United States
facility: Presbyterian Kaseman Hospital
state: New Mexico
city: Bronx
country: United States
facility: Albert Einstein College of Medicine
state: New York
city: Bronx
country: United States
facility: The North Division of Montefiore Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Brooklyn
country: United States
facility: State University of New York Downstate Medical Center
state: New York
city: Brooklyn
country: United States
facility: Maimonides Medical Center
state: New York
city: Brooklyn
country: United States
facility: Coney Island Hospital
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: East Syracuse
country: United States
facility: Hematology Oncology Associates of Central New York PC
state: New York
city: Lake Success
country: United States
facility: Monter Cancer Center
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital CCOP
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: Mount Kisco
country: United States
facility: Mount Kisco Medical Group at Northern Westchester Hospital
state: New York
city: Mount Kisco
country: United States
facility: Mount Kisco Medical Group
state: New York
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Saint Luke's Roosevelt Hospital Center - Saint Luke's Division
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: Rochester General Hospital
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Asheville
country: United States
facility: Mission Hospitals Inc
state: North Carolina
city: Charlotte
country: United States
facility: Presbyterian Hospital
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital
state: North Carolina
city: Hendersonville
country: United States
facility: Margaret R Pardee Memorial Hospital
state: North Carolina
city: High Point
country: United States
facility: High Point Regional Hospital
state: North Carolina
city: Kinston
country: United States
facility: Kinston Medical Specialists PA
state: North Carolina
city: Pinehurst
country: United States
facility: FirstHealth of the Carolinas-Moore Regional Hosiptal
state: North Carolina
city: Raleigh
country: United States
facility: Rex Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Forsyth Memorial Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Bismarck
country: United States
facility: Medcenter One Health Systems
state: North Dakota
city: Bismarck
country: United States
facility: Mid Dakota Clinic
state: North Dakota
city: Fargo
country: United States
facility: Sanford Clinic North-Fargo
state: North Dakota
city: Fargo
country: United States
facility: Sanford Medical Center-Fargo
state: North Dakota
city: Grand Forks
country: United States
facility: Altru Cancer Center
state: North Dakota
city: Minot
country: United States
facility: Trinity Cancer Care Center
state: North Dakota
city: Akron
country: United States
facility: Akron City Hospital
state: Ohio
city: Akron
country: United States
facility: Akron General Medical Center
state: Ohio
city: Canton
country: United States
facility: Aultman Health Foundation
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Kettering
country: United States
facility: Kettering Medical Center
state: Ohio
city: Portland
country: United States
facility: Legacy Good Samaritan Hospital and Medical Center
state: Oregon
city: Portland
country: United States
facility: Columbia River Oncology Program
state: Oregon
city: Portland
country: United States
facility: Kaiser Permanente
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Lancaster
country: United States
facility: Lancaster General Hospital
state: Pennsylvania
city: Paoli
country: United States
facility: Paoli Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Medical Center
state: Pennsylvania
city: Phoenixville
country: United States
facility: Phoenixville Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Reading
country: United States
facility: Saint Joseph Medical Center
state: Pennsylvania
city: State College
country: United States
facility: Mount Nittany Medical Center
state: Pennsylvania
city: West Chester
country: United States
facility: Chester County Hospital
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Hospital
state: Pennsylvania
city: Pawtucket
country: United States
facility: Memorial Hospital of Rhode Island
state: Rhode Island
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Providence
country: United States
facility: Women and Infants Hospital
state: Rhode Island
city: Anderson
country: United States
facility: AnMed Health Cancer Center
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Florence
country: United States
facility: McLeod Regional Medical Center
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Regional Medical Center
state: South Carolina
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford Clinic
state: South Dakota
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Knoxville
country: United States
facility: University of Tennessee - Knoxville
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Breast Center at One Hundred Oaks
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Austin
country: United States
facility: University Medical Center Brackenridge
state: Texas
city: Laredo
country: United States
facility: Doctor's Hospital of Laredo
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Berlin
country: United States
facility: Mountainview Medical
state: Vermont
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
city: Charlottesville
country: United States
facility: Martha Jefferson Hospital
state: Virginia
city: Lynchburg
country: United States
facility: Lynchburg Hematology-Oncology Clinic
state: Virginia
city: Longview
country: United States
facility: Saint John Medical Center
state: Washington
city: Seattle
country: United States
facility: Virginia Mason CCOP
state: Washington
city: Seattle
country: United States
facility: Pacific Medical Center-First Hill
state: Washington
city: Seattle
country: United States
facility: Group Health Cooperative
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center-First Hill
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Spokane
country: United States
facility: Rockwood Clinic
state: Washington
city: Tacoma
country: United States
facility: Northwest CCOP
state: Washington
city: Walla Walla
country: United States
facility: Providence Saint Mary Regional Cancer Center
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Medical Center
state: Washington
city: Yakima
country: United States
facility: North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
state: Washington
city: Huntington
country: United States
facility: Edwards Comprehensive Cancer Center
state: West Virginia
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Wheeling
country: United States
facility: Wheeling Hospital
state: West Virginia
city: Eau Claire
country: United States
facility: Marshfield Clinic Cancer Care at Regional Cancer Center
state: Wisconsin
city: Fond Du Lac
country: United States
facility: Central Wisconsin Cancer Program
state: Wisconsin
city: Green Bay
country: United States
facility: Saint Vincent Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: Aurora BayCare Medical Center
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Lutheran Health System/CCOP
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic
state: Wisconsin
city: Mequon
country: United States
facility: Columbia Saint Mary's Hospital - Ozaukee
state: Wisconsin
city: Milwaukee
country: United States
facility: Wheaton Franciscan Healthcare - Saint Joseph
state: Wisconsin
city: Milwaukee
country: United States
facility: Columbia Saint Mary's Water Tower Medical Commons
state: Wisconsin
city: Minocqua
country: United States
facility: Marshfield Clinic-Minocqua Center
state: Wisconsin
city: Summit
country: United States
facility: Aurora Medical Center in Summit
state: Wisconsin
city: Weston
country: United States
facility: Marshfield Clinic - Weston Center
state: Wisconsin
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Abbotsford
country: Canada
facility: BCCA - Abbotsford Centre
state: British Columbia
city: Kelowna
country: Canada
facility: BCCA - Cancer Centre for the Southern Interior
state: British Columbia
city: Surrey
country: Canada
facility: BCCA - Fraser Valley Cancer Centre
state: British Columbia
city: Vancouver
country: Canada
facility: BCCA - Vancouver Cancer Centre
state: British Columbia
city: Victoria
country: Canada
facility: BCCA - Vancouver Island Cancer Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Moncton
country: Canada
facility: The Moncton Hospital
state: New Brunswick
city: Moncton
country: Canada
facility: The Vitalite Health Network - Dr. Leon Richard
state: New Brunswick
city: Saint John
country: Canada
facility: Atlantic Health Sciences Corporation
state: New Brunswick
city: St. John's
country: Canada
facility: Dr. H. Bliss Murphy Cancer Centre
state: Newfoundland and Labrador
city: Cambridge
country: Canada
facility: Cambridge Memorial Hospital
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston
state: Ontario
city: Kitchener
country: Canada
facility: Grand River Regional Cancer Centre
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Mississauga
country: Canada
facility: Credit Valley Hospital
state: Ontario
city: Newmarket
country: Canada
facility: Stronach Regional Health Centre at Southlake
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health Oshawa
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Health Research Institute - General Division
state: Ontario
city: Sault Ste. Marie
country: Canada
facility: Algoma District Cancer Program
state: Ontario
city: St. Catharines
country: Canada
facility: Niagara Health System
state: Ontario
city: Sudbury
country: Canada
facility: Northeast Cancer Center Health Sciences
state: Ontario
city: Thunder Bay
country: Canada
facility: Thunder Bay Regional Health Science Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto East General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Odette Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: Univ. Health Network-Princess Margaret Hospital
state: Ontario
city: Toronto
country: Canada
facility: Trillium Health Centre - West Toronto
state: Ontario
city: Windsor
country: Canada
facility: Windsor Regional Cancer Centre
state: Ontario
city: Charlottetown
country: Canada
facility: PEI Cancer Treatment Centre,Queen Elizabeth Hospital
state: Prince Edward Island
city: Greenfield Park
country: Canada
facility: Hopital Charles LeMoyne
state: Quebec
city: Laval
country: Canada
facility: Hopital de la Cite-de-la-Sante
state: Quebec
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemont
state: Quebec
city: Montreal
country: Canada
facility: McGill University - Dept. Oncology
state: Quebec
city: Montreal
country: Canada
facility: CHUM - Hotel Dieu du Montreal
state: Quebec
city: Quebec City
country: Canada
facility: CHUQ-Pavillon Hotel-Dieu de Quebec
state: Quebec
city: Quebec City
country: Canada
facility: CHA-Hopital Du St-Sacrement
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
city: Chur
country: Switzerland
facility: Switzerland-Chur (Ratisches Kantons- und Regionalspital)
city: Frauenfeld
country: Switzerland
facility: Brustzentrum Thurgau, Spital Thurgau AG
city: Locarno
country: Switzerland
facility: Fondazione Oncologia Lago Maggiore, FOLM
city: Luzern 16
country: Switzerland
facility: Switzerland-Luzern (Kantonsspital Luzern)
city: Mendrisio
country: Switzerland
facility: Switzerland - Oncology Institute of Southern Switzerland (IOSI)
city: Olten
country: Switzerland
facility: Switzerland - Olten (Kantonsspital) affiliate-3101
city: St. Gallen
country: Switzerland
facility: Switzerland - ZeTup St.Gallen
city: Zurich
country: Switzerland
facility: Switzerland - Brust-Zentrum, Zurich
city: Edgbaston
country: United Kingdom
facility: University Hospital Birmingham NHS Foundation Trust
state: Birmingham
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre, Western General Hospital
state: Crewe Road South
city: Brighton
country: United Kingdom
facility: Brighton and Sussex University Hospitals NHS Trust
state: East Sussex
city: Gillingham
country: United Kingdom
facility: Medway NHS Foundation Trust
state: Kent
city: Maidstone
country: United Kingdom
facility: Kent Centre for Oncology
state: Kent
city: Middlesborough
country: United Kingdom
facility: South Tees Hospitals NHS Foundation Trust
state: Marton Road
city: Haverfordwest
country: United Kingdom
facility: Withybush General Hospital
state: Pembrokeshire
city: Middlesex
country: United Kingdom
facility: East and North Hertfordshire NHS Trust
state: Rickmansworth Road
city: Swansea
country: United Kingdom
facility: Singleton Hospital
state: Sketty Lane
city: Bristol
country: United Kingdom
facility: North Bristol NHS Trust
state: Southmead
city: London
country: United Kingdom
facility: St George's Healthcare NHS Trust
state: Tooting
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
state: University Of Dundee
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
state: Whitchurch
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: Withington
city: Birmingham
country: United Kingdom
facility: Sandwell and West Birmingham Hospitals NHS Trust
Study officials:
affiliation: Mount Sinai Hospital, Canada
name: Pamela J. Goodwin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.