Clinical trial NCT00567190: A Study to Evaluate Pertuzumab + Trastuzumab + Docetaxel vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-Positive Metastatic Breast Cancer
Official title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Pertuzumab + Trastuzumab + Docetaxel vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-Positive Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Breast Cancer
Keywords: Herceptin
Breast cancer
MBC
Taxotere
HER2
HER2 positive breast cancer
HER2 + breast cancer
HER2-positive
HER2-positive metastatic breast cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Hoffmann-La Roche
First posted: 2007-12-04
Enrollment: 808
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was a Phase III, randomized, double-blind, placebo-controlled, multicenter international clinical trial conducted to investigate the use of pertuzumab in combination with trastuzumab and docetaxel as first-line treatment for participants with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Participants could have received one prior hormonal treatment for MBC. Participants may have received systemic breast cancer treatment in the neo-adjuvant or adjuvant setting, provided that the participant had experienced a disease-free interval (DFI) of greater than or equal to (≥)12 months from completion of adjuvant systemic treatment (excluding hormonal therapy) to metastatic diagnosis. Participants may have received trastuzumab and/or a taxane during the neo-adjuvant or adjuvant treatment.

Participants were randomized in 1:1 ratio to receive either pertuzumab or placebo, along with trastuzumab and docetaxel once every 3 weeks (q3w), during the treatment phase of the study until investigator-assessed radiographic or clinical progressive disease, unmanageable toxicity, or study termination. Participants in the Placebo arm were not allowed to receive open-label pertuzumab after discontinuation from study treatment. However, if any analysis of overall survival had met the predefined criteria for statistical significance, participants in the Placebo arm still on treatment were offered the option to receive open-label pertuzumab in addition to other study medications.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease, and candidate for chemotherapy. Participants with measurable and non-measurable disease are eligible (locally recurrent disease must not be amenable to resection with curative intent; participants with de novo Stage IV disease are eligible)
* Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC)
* Left ventricular ejection fraction (LVEF) ≥50 percent (%) at baseline (within 42 days of randomization)
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
* For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective form of contraception and to continue its use for the duration of study treatment and for at least 7 months after the last dose of study treatment

Exclusion Criteria:

* History of anti-cancer therapy for MBC (with the exception of one prior hormonal regimen for MBC, which must be stopped prior to randomization)
* History of approved or investigative tyrosine kinase/HER inhibitors for breast cancer in any treatment setting, except trastuzumab used in the neoadjuvant or adjuvant setting
* History of systemic breast cancer treatment in the neo-adjuvant or adjuvant setting with a disease-free interval from completion of the systemic treatment (excluding hormonal therapy) to metastatic diagnosis of less than (\<)12 months
* History of persistent Grade ≥2 hematologic toxicity resulting from previous adjuvant therapy
* Current peripheral neuropathy of National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 3.0, Grade ≥3 at randomization
* History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent
* Current clinical or radiographic evidence of central nervous system (CNS) metastases
* Computed tomography (CT) or magnetic resonance imaging (MRI) scan of the brain is mandatory in cases of clinical suspicion of brain metastases
* History of exposure to cumulative doses of anthracyclines
* Current uncontrolled hypertension or unstable angina
* History of congestive heart failure (CHF) of any New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (exception: atrial fibrillation or paroxysmal supraventricular tachycardia)
* History of myocardial infarction within 6 months of randomization
* History of LVEF decline to below 50% during or after prior trastuzumab neo-adjuvant or adjuvant therapy
* Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy
* Inadequate organ function, as defined in the protocol, within 28 days prior to randomization
* Current severe, uncontrolled systemic disease
* Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during the course of study treatment
* Pregnant or lactating women
* History of receiving any investigational treatment within 28 days of randomization
* Current known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
* Receipt of IV antibiotics for infection within 14 days of randomization
* Current chronic daily treatment with corticosteroids (excluding inhaled steroids)
* Known hypersensitivity to any of the study drugs
* Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol

Primary outcomes:
measure: Progression-Free Survival (PFS) Determined by an Independent Review Facility
timeFrame: Tumor assessments every 9 weeks from randomization to IRF-determined PD or death from any cause, whichever occurred first, up to the primary completion date (up to 3 years, 3 months)
Secondary outcomes:
measure: Overall Survival
timeFrame: From randomization to death from any cause, up to each respective analysis data cut-off date (see the Description field for the median time on study per treatment arm)
measure: Progression-Free Survival (PFS) Determined by the Investigator
timeFrame: Tumor assessments every 9 weeks from randomization to investigator-determined PD or death from any cause, whichever occurred first (median [range] time on study in pertuzumab vs. placebo arms: 201.8 [0.7-520.0] weeks vs. 138.0 [0.4-514.7] weeks)
measure: Objective Response Determined by an Independent Review Facility
timeFrame: Tumor assessments every 9 weeks from Baseline until IRF-determined progressive disease (PD), death, or first administration of next line of anti-cancer therapy (whichever occurred first), up to the primary completion date (up to 3 years, 3 months)
measure: Duration of Objective Response Determined by an Independent Review Facility
timeFrame: From initial IRF-confirmed objective response until IRF-determined progressive disease (PD), death, or first administration of next line of anti-cancer therapy (whichever occurred first), up to the primary completion date (up to 3 years, 3 months)
measure: Time to Symptom Progression
timeFrame: Every 9 weeks from Baseline until investigator-determined progressive disease, up to the primary completion date (up to 3 years, 3 months)
measure: Overall Number of Participants Who Experienced at Least One Adverse Event, Including Serious and Non-Serious Adverse Events, by Most Severe Intensity (According to NCI-CTCAE v3.0) During the Treatment Period
timeFrame: Placebo arm: Baseline to last dose of study treatment +42 days (or crossover date); Pertuzumab arm: Baseline to last dose of study treatment +42 days; Crossover arm: Crossover date to last dose of study treatment +42 days (see Description - time per arm)
measure: Overall Number of Adverse Events by Severity (NCI-CTCAE v3.0 All Grades and Grades 3 to 5) Per 100 Patient-Years of Exposure During the Treatment Period
timeFrame: From Baseline to 42 days after the last dose of study treatment (total patient-years of exposure on study treatment in Placebo vs. Pertuzumab arms: 526.81 vs. 989.88 patient-years)
measure: Cardiac-Related AEs to Monitor: Number of Participants Who Experienced at Least One Symptomatic Left Ventricular Dysfunction (LVD), Any LVD, or Serious AE Suggestive of Congestive Heart Failure by Severity During the Treatment Period
timeFrame: Placebo arm: Baseline to last dose of study treatment +42 days (or crossover date); Pertuzumab arm: Baseline to last dose of study treatment +42 days; Crossover arm: Crossover date to last dose of study treatment +42 days (see Description - time per arm)
measure: Number of Participants Who Experienced at Least One Adverse Event to Monitor (Excluding Cardiac-Related AEs) by Severity During the Treatment Period
timeFrame: Placebo arm: Baseline to last dose of study treatment +42 days (or crossover date); Pertuzumab arm: Baseline to last dose of study treatment +42 days; Crossover arm: Crossover date to last dose of study treatment +42 days (see Description - time per arm)
measure: Overall Number of Participants Who Experienced at Least One Adverse Event Leading to Discontinuation of Any or All Study Medication
timeFrame: Placebo arm: Baseline to last dose of study treatment +42 days (or crossover date); Pertuzumab arm: Baseline to last dose of study treatment +42 days; Crossover arm: Crossover date to last dose of study treatment +42 days (see Description - time per arm)
measure: Overall Number of Participants Who Experienced at Least One Adverse Event That Resulted in Interruption or Modification of Any Study Medication
timeFrame: Placebo arm: Baseline to last dose of study treatment +42 days (or crossover date); Pertuzumab arm: Baseline to last dose of study treatment +42 days; Crossover arm: Crossover date to last dose of study treatment +42 days (see Description - time per arm)
measure: Number of Participants Who Experienced at Least One Adverse Event During the Post-Treatment Follow-Up Period
timeFrame: From Day 43 after discontinuation of all study medication to end of post-treatment follow-up period (up to 3 years)
measure: Number of Participants by Categories for the Maximum Absolute Decrease From Baseline in LVEF Value During the Treatment Period
timeFrame: Every 9 weeks from the date of randomization until Treatment Discontinuation Visit (see Description for time on study treatment per arm)
measure: Baseline LVEF Value and Change in LVEF From Baseline at Maximum Absolute Decrease Value During the Treatment Period
timeFrame: Every 9 weeks from the date of randomization until Treatment Discontinuation Visit (median [range] time on study treatment per arm: Placebo: 49.3 [0.3-514.7] weeks; Pertuzumab: 75.7 [0.6-519.6] weeks)
measure: Number of Participants With Laboratory Abnormalities in Blood Biochemistry Tests by Highest Grade According to NCI-CTCAE v3.0 During the Treatment Period
timeFrame: On Day 1 of every treatment cycle (1 cycle is 21 days) until Treatment Discontinuation Visit (see Description for time on study treatment per arm)
measure: Number of Participants With Laboratory Abnormalities in Hematology Tests by Highest Grade According to NCI-CTCAE v3.0 During the Treatment Period
timeFrame: On Day 1 (and Day 8 for some measures) of every treatment cycle (1 cycle is 21 days) until Treatment Discontinuation Visit (see Description for time on study treatment per arm)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute - Bisgrove
state: Arizona
city: Jonesboro
country: United States
facility: NEA Baptist Clinic
state: Arkansas
city: Alhambra
country: United States
facility: Central Hematology Oncology Medical Group Inc.
state: California
city: Anaheim
country: United States
facility: Pacific Cancer Medical Center
state: California
city: Bakersfield
country: United States
facility: Comprehensive Blood/Cancer Ctr
state: California
city: Baldwin Park
country: United States
facility: Kaiser Permanente - Baldwin Park
state: California
city: Beverly Hills
country: United States
facility: Tower Cancer Research Foundation
state: California
city: Campbell
country: United States
facility: South Bay Oncology Hematology Partners
state: California
city: Corona
country: United States
facility: Wilshire Oncology Medical Group
state: California
city: Fountain Valley
country: United States
facility: Compassionate Cancer Care
state: California
city: Fountain Valley
country: United States
facility: Pacific Coast Hematology/Oncology Medical Group
state: California
city: Fullerton
country: United States
facility: St. Jude Heritage Healthcare; Virgiia K.Crosson Can Ctr
state: California
city: Glendora
country: United States
facility: Wilshire Onc Med Grp., Inc
state: California
city: La Verne
country: United States
facility: Wilshire Oncology Medical Group
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Los Angeles
country: United States
facility: LAC USC Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars- Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center Clin Lab
state: California
city: Los Angeles
country: United States
facility: TORI Central Administration
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology / Oncology Clinic
state: California
city: Los Angeles
country: United States
facility: UCLA Med Ctr; Pharma Svcs
state: California
city: Modesto
country: United States
facility: Sutter Gould Medical Foundation; Clinical Research
state: California
city: Oakland
country: United States
facility: Kaiser Permanente - Oakland
state: California
city: Oxnard
country: United States
facility: Ventura County Hematology-Oncology Specialists
state: California
city: Pasadena
country: United States
facility: UCLA Healthcare/Pasadena Oncology
state: California
city: Pasadena
country: United States
facility: Wilshire Oncology Medical Group
state: California
city: Pleasant Hill
country: United States
facility: Bay Area Cancer Research Group, LLC
state: California
city: Pomona
country: United States
facility: Wilshire Oncology Medical Group
state: California
city: Rancho Cucamonga
country: United States
facility: Wilshire Oncology Medical Group
state: California
city: Sacramento
country: United States
facility: UC Davis Cancer Center; Oncology
state: California
city: San Diego
country: United States
facility: Kaiser Permanente San Diego; Hepatology Research
state: California
city: San Francisco
country: United States
facility: K. Permanente - San Fransisco
state: California
city: San Jose
country: United States
facility: K. Permanente - San Jose
state: California
city: Santa Barbara
country: United States
facility: Sansum Santa Barbara Medical Foundation Clinic
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Hematology Oncology Medical Group, Inc.
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology
state: California
city: Valencia
country: United States
facility: UCLA / Santa Clarita Valley Cancer Center
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente - Vallejo
state: California
city: Walnut Creek
country: United States
facility: K. Permanente - Walnut Creek
state: California
city: West Covina
country: United States
facility: Wilshire Oncology Medical Group
state: California
city: Whittier
country: United States
facility: Innovative clinical research institute/American institute of research
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center Lombardi Cancer Center
state: District of Columbia
city: Washington
country: United States
facility: MedStar Washington Hosp 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 Comprehensive Cancer Center
state: Florida
city: Cape Coral
country: United States
facility: Florida Cancer Specialists -Cape Coral (Cape Coral Pkwy)
state: Florida
city: Cape Coral
country: United States
facility: Florida Cancer Specialists - Cape Coral (Del Prado Blvd)
state: Florida
city: Coral Springs
country: United States
facility: Northwest Oncology/ Hematology Assoc.
state: Florida
city: Deerfield Beach
country: United States
facility: UM Sylvester Deerfield Beach; Sylvester Cancer Ctr
state: Florida
city: Englewood
country: United States
facility: Florida Cancer Specialists - Englewood
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - Fort Myers (New Hampshire Ct)
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - Broadway
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists; SCRI
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists-Broadway, Fort Myers
state: Florida
city: Gainesville
country: United States
facility: Private Practice Robert R. Carroll, Md, Pa
state: Florida
city: Hollywood
country: United States
facility: Memorial Cancer Institute
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Hospital
state: Florida
city: Lakeland
country: United States
facility: Lakeland Regional Cancer Center
state: Florida
city: Miami
country: United States
facility: Jackson Memorial Hospital
state: Florida
city: Miami
country: United States
facility: University of Miami School of Medicine
state: Florida
city: Naples
country: United States
facility: Florida Cancer Specialists - Goodlette, Naples
state: Florida
city: Naples
country: United States
facility: Florida Cancer Specialists - Pine Ridge, Naples
state: Florida
city: Orlando
country: United States
facility: Private Practice
state: Florida
city: Pembroke Pines
country: United States
facility: Breast Cancer Centre at Memorial Hospital West
state: Florida
city: Port Charlotte
country: United States
facility: Florida Cancer Specialists - Port Charlotte
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists; Sarasota
state: Florida
city: Tampa
country: United States
facility: Bay Area Oncology
state: Florida
city: Venice
country: United States
facility: Florida Cancer Specialists - Venice (S. Tamiami Tr)
state: Florida
city: Venice
country: United States
facility: Florida Cancer Specialists - Sunset Lake, Venice
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center; Oncology Research Dept-5C
state: Georgia
city: Macon
country: United States
facility: Central Georgia Hematology Oncology Associates
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital
state: Georgia
city: Warner Robins
country: United States
facility: Central GA Cancer Care
state: Georgia
city: Elmhurst
country: United States
facility: Elmhurst Hospital
state: Illinois
city: Naperville
country: United States
facility: Hematology Oncology Consultants Ltd
state: Illinois
city: Quincy
country: United States
facility: Quincy Medical Group
state: Illinois
city: Zion
country: United States
facility: Midwestern Regional Medical Center; Office of Research
state: Illinois
city: Hobart
country: United States
facility: Monroe Medical Associates - Hobart
state: Indiana
city: Hobart
country: United States
facility: St. Mary Medical Center
state: Indiana
city: Indianapolis
country: United States
facility: Hematology-Oncology of Indiana, Pc
state: Indiana
city: Munster
country: United States
facility: Community Hospital; Pharmacy
state: Indiana
city: Munster
country: United States
facility: Northwest Oncology
state: Indiana
city: Munster
country: United States
facility: Monroe Medical Associates
state: Indiana
city: Vincennes
country: United States
facility: Family Medicine Vincennes
state: Indiana
city: Iowa City
country: United States
facility: Uni of Iowa Hospital&Clinic; Holden Comprehens. Cancer Ctr
state: Iowa
city: Westwood
country: United States
facility: University of Kansas; Medical Center & Medical pavilion
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Louisville
country: United States
facility: Jewish Cancer Care
state: Kentucky
city: Lafayette
country: United States
facility: Cancer Center of Acadiana at Lafayette General
state: Louisiana
city: Shreveport
country: United States
facility: Christus Schumpert Health System
state: Louisiana
city: Bethesda
country: United States
facility: Private Practice- Carolyn Hendricks, MD
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Pittsfield
country: United States
facility: Berkshire Hematology, Oncology Pc
state: Massachusetts
city: Grand Rapids
country: United States
facility: Cancer & Hematology Centers of Western Michigan
state: Michigan
city: Grand Rapids
country: United States
facility: Cancer & Hematology Center of West Michigan
state: Michigan
city: Saint Joseph
country: United States
facility: Oncology Care Associates PLLC
state: Michigan
city: Edina
country: United States
facility: Southdale Cancer Clinic U of M Medical Center, Fairview- Edina
state: Minnesota
city: Minneapolis
country: United States
facility: US Oncology Research at Minnesota Oncology
state: Minnesota
city: Minneapolis
country: United States
facility: Minneapolis Oncology Hamatology PA
state: Minnesota
city: New Albany
country: United States
facility: The Jones Clinic, PC
state: Mississippi
city: Billings
country: United States
facility: St. Vincent Frontier Cancer Center
state: Montana
city: Lincoln
country: United States
facility: Southeast Nebraska Cancer Center;; Southeast Nebraska Hematology and Oncology
state: Nebraska
city: Norfolk
country: United States
facility: Norfolk Oncology Consultants
state: Nebraska
city: Omaha
country: United States
facility: Hematology-Oncology Consultants, Pc
state: Nebraska
city: Las Vegas
country: United States
facility: Southern Nevada Cancer Research Foundation
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Livingston
country: United States
facility: St. Barnabas Cancer Center
state: New Jersey
city: Mountain Lakes
country: United States
facility: Oncology and Hematology Specialists
state: New Jersey
city: Farmington
country: United States
facility: San Juan Oncology Associates
state: New Mexico
city: Brockport
country: United States
facility: Brockport-Interlakes Foundation
state: New York
city: Canandaigua
country: United States
facility: Canandaigua-Interlakes Found
state: New York
city: Geneva
country: United States
facility: Geneva-Interlakes Foundation
state: New York
city: Lake Success
country: United States
facility: ProHEALTH Care Associates LLP
state: New York
city: New York
country: United States
facility: Beth Israel Comprehensive Cancer Center Pharmacy
state: New York
city: New York
country: United States
facility: The Women'sOncology & Wellness Practice
state: New York
city: Rochester
country: United States
facility: Upstate Ny Cancer Research & Education Foundation
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Hickory
country: United States
facility: Carolina Oncology Specialists, PA - Hickory
state: North Carolina
city: Huntersville
country: United States
facility: Carolina BioOncology Institute, PLCC
state: North Carolina
city: Lenoir
country: United States
facility: NW Carolina Onc & Hem
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc
state: Ohio
city: Columbus
country: United States
facility: Hema Onc Conslts-Grant Ave
state: Ohio
city: Columbus
country: United States
facility: The Mark H. Zangmeister Ctr; Mid Ohio Onc/Hem Inc.
state: Ohio
city: Columbus
country: United States
facility: Hematology Onc Consultants
state: Ohio
city: Dover
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Granville
country: United States
facility: Hematology Oncology Consultants (NWK)
state: Ohio
city: Toledo
country: United States
facility: Medical College of Ohio; Cancer Institute
state: Ohio
city: Oklahoma City
country: United States
facility: Mercy Physicians of Oklahoma
state: Oklahoma
city: Tulsa
country: United States
facility: CA Care Associates-OK Oncology and Hematology
state: Oklahoma
city: Tulsa
country: United States
facility: Cancer Care Assoc-S. Ingo
state: Oklahoma
city: Tulsa
country: United States
facility: OK Oncology & Hematology PC
state: Oklahoma
city: Darby
country: United States
facility: Cons in Med Onc and Hem
state: Pennsylvania
city: Drexel Hill
country: United States
facility: Consultants in Medical Oncology/Hematology
state: Pennsylvania
city: Kittanning
country: United States
facility: Armstrong County Memorial Hospital
state: Pennsylvania
city: Newtown Square
country: United States
facility: Conslts in Med Onc (Newtown); Bryn Mawr Health Canc Ctr
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Uni of Pittsburgh; Magee-Women'S Hospital
state: Pennsylvania
city: Ridley Park
country: United States
facility: Consultants Med Onc & Hem
state: Pennsylvania
city: Chattanooga
country: United States
facility: Erlanger Health System; Oncology Research
state: Tennessee
city: Chattanooga
country: United States
facility: SCRI Tennessee Oncology Chattanooga
state: Tennessee
city: Johnson City
country: United States
facility: McLeod Cancer and Blood Center
state: Tennessee
city: Knoxville
country: United States
facility: University of Tennessee Cancer Institute;Hem-Onc Consultants
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center - Tennessee Oncology, Pllc
state: Tennessee
city: Houston
country: United States
facility: Park Plaza
state: Texas
city: Houston
country: United States
facility: Southwest
state: Texas
city: Houston
country: United States
facility: St. Joseph's
state: Texas
city: Houston
country: United States
facility: Memorial City-Main Office
state: Texas
city: Houston
country: United States
facility: Oncology Consultants
state: Texas
city: Houston
country: United States
facility: St. Luke's
state: Texas
city: Houston
country: United States
facility: Willowbrook
state: Texas
city: Katy
country: United States
facility: Katy-Christus St. Catherine
state: Texas
city: San Antonio
country: United States
facility: South Texas Oncology Hematology
state: Texas
city: Sugar Land
country: United States
facility: Oncology Consultants - Sugar Land
state: Texas
city: Ogden
country: United States
facility: Northern Utah Associates
state: Utah
city: Rutland
country: United States
facility: Community Cancer Center Rutland Regional Medical Center
state: Vermont
city: Bristol
country: United States
facility: Wellmonth Physician Services
state: Virginia
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Walla Walla
country: United States
facility: St. Mary Medical Center
state: Washington
city: Buenos Aires
country: Argentina
facility: Sanatorio Güemes; Oncología
city: Buenos Aires
country: Argentina
facility: Centro de Oncologia e Investigacion Buenos Aires (COIBA)
city: Caba
country: Argentina
facility: Instituto Medico Especializado (IME); Oncologia
city: Chaco-resistencia
country: Argentina
facility: Center Instituto Médico Privado I.M.P.; Oncology
city: La Plata
country: Argentina
facility: Policlinica Privada Site la Plata SA; Oncology
city: Neuquén
country: Argentina
facility: Unidad Oncológica De Neuquén
city: Rosario
country: Argentina
facility: Hosp Provincial D. Centenarios; Oncology Dept
city: Salvador
country: Brazil
facility: Clinica Amo - Assistencia Medica Em Oncologia
state: BA
city: Fortaleza
country: Brazil
facility: Crio - Centro Regional Integrado de Oncologia
state: CE
city: Goiania
country: Brazil
facility: Centro Goiano de Oncologia - CGO
state: GO
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Cancer - INCa; Oncologia
state: RJ
city: Rio de Janeiro
country: Brazil
facility: Hospital Universitario Clementino Fraga Filho - UFRJ; Oncologia
state: RJ
city: Ijui
country: Brazil
facility: Hospital de Caridade de Ijui; Oncologia
state: RS
city: Porto Alegre
country: Brazil
facility: Santa Casa de Misericordia de Porto Alegre
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas - UFRGS
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao
state: RS
city: Jau
country: Brazil
facility: Hospital Amaral Carvalho
state: SP
city: Ribeirao Preto
country: Brazil
facility: Hospital das Clinicas - FMUSP Ribeirao Preto
state: SP
city: Santo Andre
country: Brazil
facility: Faculdade de Medicina do ABC - FMABC; Oncologia e Hematologia
state: SP
city: Santos
country: Brazil
facility: Iso - Inst. Santista de Oncologia
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer Arnaldo Vieira de Carvalho - ICAVC; Pesquisa Clinica
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital Perola Byington
state: SP
city: Sao Paulo
country: Brazil
facility: Inst. Brasileiro de Controle Ao Cancer; Oncologia Clinica / Quimioterapia
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital Estadual do Servidor Publico
state: SP
city: Sorocaba
country: Brazil
facility: Instituto de Oncologia de Sorocaba - CEPOS
state: SP
city: Toronto
country: Canada
facility: St. Michael'S Hospital
state: Ontario
city: Changchun
country: China
facility: Jilin Cancer Hospital
city: Fuzhou
country: China
facility: Fuzhou General Hospital, PLA Nanjing Military Area Command
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Shanghai City
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Shanghai First People's Hospital
city: San Jose
country: Costa Rica
facility: Hospital Cima San Jose; Oncology
city: Zagreb
country: Croatia
facility: Clinical Hospital Sisters of Mercy
city: Zagreb
country: Croatia
facility: University Hospital Centre Zagreb; Clinic For Oncology
city: Guayaquil
country: Ecuador
facility: Solca Guayaquil- Sociedad de Lucha Contra El Cáncer; Oncology
city: Guayaquil
country: Ecuador
facility: Teodoro Maldonado Carbo Hospital; Oncology Service
city: Quito
country: Ecuador
facility: Hospital Carlos Andrade Marin; Servicio de Oncología
city: Quito
country: Ecuador
facility: Hospital Solca Quito; Oncologia
city: Tampere
country: Finland
facility: Tampere University Hospital; Dept of Oncology
city: Turku
country: Finland
facility: Turku Uni Central Hospital; Oncology Clinics
city: Bayonne
country: France
facility: Centre Oncologie Du Pays Basque
city: Bordeaux
country: France
facility: Clinique Tivoli; Sce Radiotherapie
city: Dijon
country: France
facility: Centre Georges Francois Leclerc; Oncologie 3
city: La Roche Sur Yon
country: France
facility: Centre Hospitalier Departemental Les Oudairies
city: Le Mans
country: France
facility: Centre Jean Bernard
city: Nice
country: France
facility: Centre Antoine Lacassagne; Hopital De Jour A2
city: Saint Herblain
country: France
facility: Ico Rene Gauducheau; Oncologie
city: Salouel
country: France
facility: Groupe Hospitalier Sud; Oncologie Radiotherapie
city: Berlin
country: Germany
facility: Onkologischer Schwerpunkt am Oskar-Helene-Heim; Dres. Herrenberger, Keitel-Wittig u. Kirsch
city: Bielefeld
country: Germany
facility: Onkologische Schwerpunktpraxis Bielefeld; Haemotologie & Internistische onkologie
city: Essen
country: Germany
facility: Universitätsklinikum Essen; Zentrum Für Frauenheilkunde
city: Halle
country: Germany
facility: Universitätsklinikum Halle (Saale); Universitätsklinik Und Poliklinik Für Gynäkologie
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf; Frauenklinik
city: Heidelberg
country: Germany
facility: Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg
city: Koeln
country: Germany
facility: St. Elisabeth Krankenhaus Köln GmbH; Gynäkologie und Geburtshilfe
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz; Klinik u. Poliklinik f. Geburtshilfe u. Frauenheilkunde
city: Rheinfelden
country: Germany
facility: Krankenhaus Rheinfelden; Frauenklinik
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus; Hämatologie, Onkologie und Palliativmedizin
city: Trier
country: Germany
facility: Klinikum Mutterhaus der Borromaeerinnen gGmbH; Haematologie/Onkologie
city: Tübingen
country: Germany
facility: Universitätsklinik Tübingen; Frauenklinik
city: Wuerselen
country: Germany
facility: Haematologisch-Onkologische Praxis; Dr. med. Christoph Maintz und Matthias Groschek
city: Guatemala City
country: Guatemala
facility: Grupo Angeles
city: Guatemala City
country: Guatemala
facility: Therapeutic Research Inst. & Lab S.A. (Trial)
city: Guatemala
country: Guatemala
facility: Centro Oncologico S.A.
city: Hong Kong
country: Hong Kong
facility: Pamela Youde Nethersole Eastern Hospital; Clinical Oncology
city: Shatin
country: Hong Kong
facility: Prince of Wales Hosp; Dept. Of Clinical Onc
city: Chieti
country: Italy
facility: Policlinico Ospedaliero Ss Annunziata; U.O. Di Clinica Oncologica
state: Abruzzo
city: Meldola
country: Italy
facility: IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
state: Emilia-Romagna
city: Ravenna
country: Italy
facility: Ospedale Provinciale Santa Maria delle Croci
state: Emilia-Romagna
city: Frosinone
country: Italy
facility: Ausl Frosinone - Ospedale Umberto I; Divisione Di Oncologia
state: Lazio
city: Brescia
country: Italy
facility: Az. Osp. Spedali Civili; Divisione Di Oncologia - Iii Medicina
state: Lombardia
city: Macerata
country: Italy
facility: Ospedale Di Macerata; Oncologia
state: Marche
city: Candiolo
country: Italy
facility: Fondazione Del Piemonte Per L'oncologia IRCC Di Candiolo
state: Piemonte
city: Brindisi
country: Italy
facility: Ospedale Antonio Perrino; Oncologia Medica
state: Puglia
city: Antella (FI)
country: Italy
facility: Azienda Sanitaria S. Maria Annunziata; S. C. Oncologia Medica
state: Toscana
city: Prato
country: Italy
facility: Ospedale Misericordia E Dolce; Oncologia Medica
state: Toscana
city: Aichi
country: Japan
facility: Aichi Cancer Center Hospital, Breast Oncology
city: Chiba
country: Japan
facility: Chiba Cancer Center; Breast Surgical Oncology
city: Chiba
country: Japan
facility: National Cancer Center Hospital East; Breast and Medical Oncology
city: Ehime
country: Japan
facility: Natl Hosp Org Shikoku; Cancer Ctr, Surgery
city: Fukuoka
country: Japan
facility: Kitakyushu Municipal Medical Center, Surgery
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center;Breast Oncology
city: Gunma
country: Japan
facility: Gunma University Hospital; Department of Thoracic and Visceral Organ Surgery
city: Iwate
country: Japan
facility: Iwate Med Univ School of Med; Surgery
city: Kagoshima
country: Japan
facility: Sagara Hospital; Breast Surgery
city: Kanagawa
country: Japan
facility: St. Marianna University School of Medicine Hospital, Breast and Endocrine Surgery
city: Kanagawa
country: Japan
facility: Tokai University Hospital, Breast and Endocrine Surgery
city: Kumamoto
country: Japan
facility: Kumamoto City Hospital, Breast and Endocrine Surgery
city: Kumamoto
country: Japan
facility: Kumamoto Shinto General Hospital; Breast Cancer Center
city: Kyoto
country: Japan
facility: Kyoto University Hospital; Breast Surgery
city: Niigata
country: Japan
facility: Niigata Cancer Ctr Hospital; Breast Surgery
city: Osaka
country: Japan
facility: OSAKA CITY GENERAL HOSPITAL;Medical Oncology
city: Osaka
country: Japan
facility: National Hospital Organization Osaka National Hospital; Breast Surgery
city: Osaka
country: Japan
facility: Osaka University Hospital; Breast and Endocrine Surgery
city: Saitama
country: Japan
facility: Saitama Medical University International Medical Center; Medical Oncology
city: Saitama
country: Japan
facility: Saitama Cancer Center, Breast Oncology
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center; Female Internal Medicine
city: Shizuoka
country: Japan
facility: Shizuoka General Hospital; Breast Surgery
city: Tochigi
country: Japan
facility: Jichi Medical University; Dept of Clinical Oncology
city: Tokyo
country: Japan
facility: National Cancer Center Hospital; Breast and Medical Oncology
city: Tokyo
country: Japan
facility: St. Luke's Internat. Hospital, Breast Surgical Oncology
city: Tokyo
country: Japan
facility: Tokyo Metropolitan; Komagome Hospital, Surgery
city: Tokyo
country: Japan
facility: The Cancer Inst. Hosp. of JFCR; Breast Oncology Center
city: Tokyo
country: Japan
facility: Tokyo Medical Uni. Hospital; Breast Oncology
city: Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center; Medical Oncology
city: Seoul
country: Korea, Republic of
facility: Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology
city: Seoul
country: Korea, Republic of
facility: Yonsei Uni College of Medicine, Severance Hospital; Internal Medicine Dept.
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Centre; Division of Hematology/Oncology
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center, Uni Ulsan Collegemedicine; Dept.Internal Medicine / Divisionhematology/Oncology
city: Daugavpils
country: Latvia
facility: Daugavpils Regional Hospital
city: Riga
country: Latvia
facility: Rigas Austrumu Kliniska Universitates slimnica, Latvijas Onkologijas centrs
city: Riga
country: Latvia
facility: P.Stradins Clinical University Hospital, Oncology Centre
city: Mexico City
country: Mexico
facility: Hospital Angeles Metropolitano; Room 220
state: Mexico CITY (federal District)
city: Toluca
country: Mexico
facility: Centro Oncologico Estatal ISSEMYM
city: Bitola
country: North Macedonia
facility: Clinical Hospital; Oncology Department
city: Skopje
country: North Macedonia
facility: Institute of Radiotherapy Oncology
city: Skopje
country: North Macedonia
facility: Private Health Organization Acibadem Sistina Hospital
city: Cebu City
country: Philippines
facility: Cebu Cancer Institute; Perpetual Succour Hospital
city: Quezon City
country: Philippines
facility: Veterans Memorial Medical Center; Oncology
city: Quezon City
country: Philippines
facility: St Luke'S Medical Centre; Oncology
city: Lublin
country: Poland
facility: Samodzielny Publiczny Kliniczny Nr 1 W Lublinie; Klinika Chirurgii Onkologicznej
city: Lublin
country: Poland
facility: COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej
city: Poznan
country: Poland
facility: Oddzial Chemioterapii Szpitala Klinicznego Nr 1 w Poznaniu
city: Szczecin
country: Poland
facility: Zachodniopomorskie Centrum Onkologii, Osrodek Innowacyjnosci, Rozwoju i Badan Klinicznych
city: Warszawa
country: Poland
facility: Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii
city: St Petersburg
country: Russian Federation
facility: FSBI"National Medical Research Center of Oncology named after N.N.Petrov" MHRF
state: Leningrad
city: Ivanovo
country: Russian Federation
facility: Ivanovo Regional Oncology Dispensary
city: Kislino, Kursk Region
country: Russian Federation
facility: Regional Oncology Hospital Of Kursk; Chemotherapy
city: Moscow
country: Russian Federation
facility: Blokhin Cancer Research Center; Combined Treatment
city: Moscow
country: Russian Federation
facility: Russian Oncology Research Center n.a. N.N. Blokhin Dpt of Clinical Pharmacology and Chemotherapy
city: Omsk
country: Russian Federation
facility: Omsk Region Clinical Oncology Dispensary; 1St Sergical Department
city: Orenburg
country: Russian Federation
facility: State Inst. Of Healthcare Orenburg Regional Clinical Oncology Dis
city: Samara
country: Russian Federation
facility: SBI of Healthcare Samara Regional Clinical Oncology Dispensary
city: St Petersburg
country: Russian Federation
facility: SBI of Healthcare Leningrad Regional Oncology Dispensary
city: Singapore
country: Singapore
facility: National University Hospital; National University Cancer Institute, Singapore (NCIS)
city: Singapore
country: Singapore
facility: National Cancer Centre; Medical Oncology
city: La Laguna
country: Spain
facility: Hospital Universitario de Canarias;servicio de Oncologia
state: Tenerife
city: Barcelona
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
city: Barcelona
country: Spain
facility: Hospital Duran i Reynals; Oncologia
city: Jaen
country: Spain
facility: Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia
city: La Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología
city: Lerida
country: Spain
facility: Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia
city: Madrid
country: Spain
facility: Centro Oncologico MD Anderson Internacional; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre; Servicio de Oncologia
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
city: Bangkok
country: Thailand
facility: Chulalongkorn Hospital; Medical Oncology
city: Bangkok
country: Thailand
facility: National Cancer Inst.
city: Bangkok
country: Thailand
facility: Rajavithi Hospital; Division of Medical Oncology
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc
city: Bangkok
country: Thailand
facility: Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology
city: Songkhla
country: Thailand
facility: Songklanagarind Hospital; Department of Oncology
city: Chelmsford
country: United Kingdom
facility: Broomfield Hospital; Oncology
city: Leeds
country: United Kingdom
facility: St James Uni Hospital; Icrf Cancer Medicine Research Unit
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary; Dept. of Medical Oncology
city: London
country: United Kingdom
facility: St. Bartholomew'S Hospital; Dept of Medical Oncology
city: London
country: United Kingdom
facility: Royal Free Hospital; Dept of Oncology
city: London
country: United Kingdom
facility: St George'S Hospital; Oncology Research Office /Oncology Opd
city: London
country: United Kingdom
facility: Charing Cross Hospital; Medical Oncology.
city: Northwood
country: United Kingdom
facility: Mount Vernon Hospital; Centre For Cancer Treatment
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital; Dept of Clinical Oncology
city: Westcliffe-on-sea
country: United Kingdom
facility: Southend Hospital; Oncology Dept
city: Wirral
country: United Kingdom
facility: The Clatterbridge Cancer Ctr For Oncolgy
Study officials:
affiliation: Genentech, Inc./Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19. doi: 10.1056/NEJMoa1113216. Epub 2011 Dec 7.
citation: Swain SM, Miles D, Kim SB, Im YH, Im SA, Semiglazov V, Ciruelos E, Schneeweiss A, Loi S, Monturus E, Clark E, Knott A, Restuccia E, Benyunes MC, Cortes J; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Apr;21(4):519-530. doi: 10.1016/S1470-2045(19)30863-0. Epub 2020 Mar 12.
citation: Miles D, Im YH, Fung A, Yoo B, Knott A, Heeson S, Beattie MS, Swain SM. Effect of docetaxel duration on clinical outcomes: exploratory analysis of CLEOPATRA, a phase III randomized controlled trial. Ann Oncol. 2017 Nov 1;28(11):2761-2767. doi: 10.1093/annonc/mdx406.
citation: Swain SM, Schneeweiss A, Gianni L, Gao JJ, Stein A, Waldron-Lynch M, Heeson S, Beattie MS, Yoo B, Cortes J, Baselga J. Incidence and management of diarrhea in patients with HER2-positive breast cancer treated with pertuzumab. Ann Oncol. 2017 Apr 1;28(4):761-768. doi: 10.1093/annonc/mdw695.
citation: Luen SJ, Salgado R, Fox S, Savas P, Eng-Wong J, Clark E, Kiermaier A, Swain SM, Baselga J, Michiels S, Loi S. Tumour-infiltrating lymphocytes in advanced HER2-positive breast cancer treated with pertuzumab or placebo in addition to trastuzumab and docetaxel: a retrospective analysis of the CLEOPATRA study. Lancet Oncol. 2017 Jan;18(1):52-62. doi: 10.1016/S1470-2045(16)30631-3. Epub 2016 Dec 7.
citation: Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortes J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19;372(8):724-34. doi: 10.1056/NEJMoa1413513.
citation: Baselga J, Cortes J, Im SA, Clark E, Ross G, Kiermaier A, Swain SM. Biomarker analyses in CLEOPATRA: a phase III, placebo-controlled study of pertuzumab in human epidermal growth factor receptor 2-positive, first-line metastatic breast cancer. J Clin Oncol. 2014 Nov 20;32(33):3753-61. doi: 10.1200/JCO.2013.54.5384. Epub 2014 Oct 20.
citation: Swain SM, Baselga J, Miles D, Im YH, Quah C, Lee LF, Cortes J. Incidence of central nervous system metastases in patients with HER2-positive metastatic breast cancer treated with pertuzumab, trastuzumab, and docetaxel: results from the randomized phase III study CLEOPATRA. Ann Oncol. 2014 Jun;25(6):1116-21. doi: 10.1093/annonc/mdu133. Epub 2014 Mar 31.
citation: Miles D, Baselga J, Amadori D, Sunpaweravong P, Semiglazov V, Knott A, Clark E, Ross G, Swain SM. Treatment of older patients with HER2-positive metastatic breast cancer with pertuzumab, trastuzumab, and docetaxel: subgroup analyses from a randomized, double-blind, placebo-controlled phase III trial (CLEOPATRA). Breast Cancer Res Treat. 2013 Nov;142(1):89-99. doi: 10.1007/s10549-013-2710-z. Epub 2013 Oct 16.
citation: Cortes J, Baselga J, Im YH, Im SA, Pivot X, Ross G, Clark E, Knott A, Swain SM. Health-related quality-of-life assessment in CLEOPATRA, a phase III study combining pertuzumab with trastuzumab and docetaxel in metastatic breast cancer. Ann Oncol. 2013 Oct;24(10):2630-2635. doi: 10.1093/annonc/mdt274. Epub 2013 Jul 17.
citation: Swain SM, Kim SB, Cortes J, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Knott A, Clark E, Ross G, Benyunes MC, Baselga J. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013 May;14(6):461-71. doi: 10.1016/S1470-2045(13)70130-X. Epub 2013 Apr 18.
citation: Baselga J, Swain SM. CLEOPATRA: a phase III evaluation of pertuzumab and trastuzumab for HER2-positive metastatic breast cancer. Clin Breast Cancer. 2010 Dec 1;10(6):489-91. doi: 10.3816/CBC.2010.n.065.