A Study to Evaluate Pertuzumab + Trastuzumab + Docetaxel vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-Positive Metastatic Breast Cancer

Metastatic Breast Cancer Clinical Trial

— CLEOPATRA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00567190
• Other study ID #: TOC4129g
• Secondary ID: WO206982007-0029
• Status: Completed
• Phase: Phase 3
• Start date: February 12, 2008
• Est. completion date: November 23, 2018

Study information

• Verified date: December 2019
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 808
• Est. completion date: November 23, 2018
• Est. primary completion date: May 13, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Pertuzumab
Pertuzumab was administered as an intravenous (IV) loading dose of 840 milligrams (mg) q3w on Day 1 of Cycle 1 (1 Cycle length = 21 days), and 420 mg q3w on Day 1 of subsequent cycles until investigator-assessed radiographic or clinical progressive disease, unmanageable toxicity, or study termination.
• Placebo
Placebo (matching pertuzumab) was administered intravenously.
• Trastuzumab
Trastuzumab was administered as an IV loading dose of 8 milligrams per kilogram (mg/kg) q3w on Day 2 of Cycle 1 (1 Cycle length = 21 days), and 6 mg/kg q3w on Day 1 of subsequent cycles until investigator-assessed radiographic or clinical progressive disease, unmanageable toxicity, or study termination.
• Docetaxel
Docetaxel was administered as an IV dose of 75 milligrams per square meter of body surface area (mg/m^2) q3w on Day 2 of Cycle 1 (1 Cycle length = 21 days), and 75 mg/m^2 (up to 100 mg/m^2 as per treating physician discretion) q3w on Day 1 of subsequent cycles until investigator-assessed radiographic or clinical progressive disease, unmanageable toxicity, or study termination. On or prior to Cycle 6, docetaxel was only to be discontinued for progressive disease or unmanageable toxicity. After Cycle 6, continuation of docetaxel treatment was at the discretion of the participant and treating physician.

Locations

Country	Name	City	State
Argentina	Centro de Oncologia e Investigacion Buenos Aires (COIBA)	Buenos Aires
Argentina	Sanatorio Güemes; Oncología	Buenos Aires
Argentina	Instituto Medico Especializado (IME); Oncologia	Caba
Argentina	Center Instituto Médico Privado I.M.P.; Oncology	Chaco-resistencia
Argentina	Policlinica Privada Site la Plata SA; Oncology	La Plata
Argentina	Unidad Oncológica De Neuquén	Neuquén
Argentina	Hosp Provincial D. Centenarios; Oncology Dept	Rosario
Brazil	Crio - Centro Regional Integrado de Oncologia	Fortaleza	CE
Brazil	Centro Goiano de Oncologia - CGO	Goiania	GO
Brazil	Hospital de Caridade de Ijui; Oncologia	Ijui	RS
Brazil	Hospital Amaral Carvalho	Jau	SP
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS
Brazil	Santa Casa de Misericordia de Porto Alegre	Porto Alegre	RS
Brazil	Hospital das Clinicas - FMUSP Ribeirao Preto	Ribeirao Preto	SP
Brazil	Hospital Universitario Clementino Fraga Filho - UFRJ; Oncologia	Rio de Janeiro	RJ
Brazil	Instituto Nacional de Cancer - INCa; Oncologia	Rio de Janeiro	RJ
Brazil	Clinica Amo - Assistencia Medica Em Oncologia	Salvador	BA
Brazil	Faculdade de Medicina do ABC - FMABC; Oncologia e Hematologia	Santo Andre	SP
Brazil	Iso - Inst. Santista de Oncologia	Santos	SP
Brazil	Hospital Estadual do Servidor Publico	Sao Paulo	SP
Brazil	Hospital Perola Byington	Sao Paulo	SP
Brazil	Inst. Brasileiro de Controle Ao Cancer; Oncologia Clinica / Quimioterapia	Sao Paulo	SP
Brazil	Instituto do Cancer Arnaldo Vieira de Carvalho - ICAVC; Pesquisa Clinica	Sao Paulo	SP
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Brazil	Instituto de Oncologia de Sorocaba - CEPOS	Sorocaba	SP
Canada	St. Michael'S Hospital	Toronto	Ontario
China	Jilin Cancer Hospital	Changchun
China	Fuzhou General Hospital, PLA Nanjing Military Area Command	Fuzhou
China	Zhejiang Cancer Hospital	Hangzhou
China	Shanghai First People's Hospital	Shanghai
China	Fudan University Shanghai Cancer Center	Shanghai City
Costa Rica	Hospital Cima San Jose; Oncology	San Jose
Croatia	Clinical Hospital Sisters of Mercy	Zagreb
Croatia	University Hospital Centre Zagreb; Clinic For Oncology	Zagreb
Ecuador	Solca Guayaquil- Sociedad de Lucha Contra El Cáncer; Oncology	Guayaquil
Ecuador	Teodoro Maldonado Carbo Hospital; Oncology Service	Guayaquil
Ecuador	Hospital Carlos Andrade Marin; Servicio de Oncología	Quito
Ecuador	Hospital Solca Quito; Oncologia	Quito
Finland	Tampere University Hospital; Dept of Oncology	Tampere
Finland	Turku Uni Central Hospital; Oncology Clinics	Turku
France	Centre Oncologie Du Pays Basque	Bayonne
France	Clinique Tivoli; Sce Radiotherapie	Bordeaux
France	Centre Georges Francois Leclerc; Oncologie 3	Dijon
France	Centre Hospitalier Departemental Les Oudairies	La Roche Sur Yon
France	Centre Jean Bernard	Le Mans
France	Centre Antoine Lacassagne; Hopital De Jour A2	Nice
France	Ico Rene Gauducheau; Oncologie	Saint Herblain
France	Groupe Hospitalier Sud; Oncologie Radiotherapie	Salouel
Germany	Onkologischer Schwerpunkt am Oskar-Helene-Heim; Dres. Herrenberger, Keitel-Wittig u. Kirsch	Berlin
Germany	Onkologische Schwerpunktpraxis Bielefeld; Haemotologie & Internistische onkologie	Bielefeld
Germany	Universitätsklinikum Essen; Zentrum Für Frauenheilkunde	Essen
Germany	Universitätsklinikum Halle (Saale); Universitätsklinik Und Poliklinik Für Gynäkologie	Halle
Germany	Universitätsklinikum Hamburg-Eppendorf; Frauenklinik	Hamburg
Germany	Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg	Heidelberg
Germany	St. Elisabeth Krankenhaus Köln GmbH; Gynäkologie und Geburtshilfe	Koeln
Germany	Universitätsmedizin Mainz; Klinik u. Poliklinik f. Geburtshilfe u. Frauenheilkunde	Mainz
Germany	Krankenhaus Rheinfelden; Frauenklinik	Rheinfelden
Germany	Robert-Bosch-Krankenhaus; Hämatologie, Onkologie und Palliativmedizin	Stuttgart
Germany	Klinikum Mutterhaus der Borromaeerinnen gGmbH; Haematologie/Onkologie	Trier
Germany	Universitätsklinik Tübingen; Frauenklinik	Tübingen
Germany	Haematologisch-Onkologische Praxis; Dr. med. Christoph Maintz und Matthias Groschek	Wuerselen
Guatemala	Centro Oncologico S.A.	Guatemala
Guatemala	Grupo Angeles	Guatemala City
Guatemala	Therapeutic Research Inst. & Lab S.A. (Trial)	Guatemala City
Hong Kong	Pamela Youde Nethersole Eastern Hospital; Clinical Oncology	Hong Kong
Hong Kong	Prince of Wales Hosp; Dept. Of Clinical Onc	Shatin
Italy	Azienda Sanitaria S. Maria Annunziata; S. C. Oncologia Medica	Antella (FI)	Toscana
Italy	Az. Osp. Spedali Civili; Divisione Di Oncologia - Iii Medicina	Brescia	Lombardia
Italy	Ospedale Antonio Perrino; Oncologia Medica	Brindisi	Puglia
Italy	Fondazione Del Piemonte Per L'oncologia IRCC Di Candiolo	Candiolo	Piemonte
Italy	Policlinico Ospedaliero Ss Annunziata; U.O. Di Clinica Oncologica	Chieti	Abruzzo
Italy	Ausl Frosinone - Ospedale Umberto I; Divisione Di Oncologia	Frosinone	Lazio
Italy	Ospedale Di Macerata; Oncologia	Macerata	Marche
Italy	IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica	Meldola	Emilia-Romagna
Italy	Ospedale Misericordia E Dolce; Oncologia Medica	Prato	Toscana
Italy	Ospedale Provinciale Santa Maria delle Croci	Ravenna	Emilia-Romagna
Japan	Aichi Cancer Center Hospital, Breast Oncology	Aichi
Japan	Chiba Cancer Center; Breast Surgical Oncology	Chiba
Japan	National Cancer Center Hospital East; Breast and Medical Oncology	Chiba
Japan	Natl Hosp Org Shikoku; Cancer Ctr, Surgery	Ehime
Japan	Kitakyushu Municipal Medical Center, Surgery	Fukuoka
Japan	National Hospital Organization Kyushu Cancer Center;Breast Oncology	Fukuoka
Japan	Gunma University Hospital; Department of Thoracic and Visceral Organ Surgery	Gunma
Japan	Iwate Med Univ School of Med; Surgery	Iwate
Japan	Sagara Hospital; Breast Surgery	Kagoshima
Japan	St. Marianna University School of Medicine Hospital, Breast and Endocrine Surgery	Kanagawa
Japan	Tokai University Hospital, Breast and Endocrine Surgery	Kanagawa
Japan	Kumamoto City Hospital, Breast and Endocrine Surgery	Kumamoto
Japan	Kumamoto Shinto General Hospital; Breast Cancer Center	Kumamoto
Japan	Kyoto University Hospital; Breast Surgery	Kyoto
Japan	Niigata Cancer Ctr Hospital; Breast Surgery	Niigata
Japan	National Hospital Organization Osaka National Hospital; Breast Surgery	Osaka
Japan	OSAKA CITY GENERAL HOSPITAL;Medical Oncology	Osaka
Japan	Osaka University Hospital; Breast and Endocrine Surgery	Osaka
Japan	Saitama Cancer Center, Breast Oncology	Saitama
Japan	Saitama Medical University International Medical Center; Medical Oncology	Saitama
Japan	Shizuoka Cancer Center; Female Internal Medicine	Shizuoka
Japan	Shizuoka General Hospital; Breast Surgery	Shizuoka
Japan	Jichi Medical University; Dept of Clinical Oncology	Tochigi
Japan	National Cancer Center Hospital; Breast and Medical Oncology	Tokyo
Japan	St. Luke's Internat. Hospital, Breast Surgical Oncology	Tokyo
Japan	The Cancer Inst. Hosp. of JFCR; Breast Oncology Center	Tokyo
Japan	Tokyo Medical Uni. Hospital; Breast Oncology	Tokyo
Japan	Tokyo Metropolitan; Komagome Hospital, Surgery	Tokyo
Korea, Republic of	National Cancer Center; Medical Oncology	Gyeonggi-do
Korea, Republic of	Asan Medical Center, Uni Ulsan Collegemedicine; Dept.Internal Medicine / Divisionhematology/Oncology	Seoul
Korea, Republic of	Samsung Medical Centre; Division of Hematology/Oncology	Seoul
Korea, Republic of	Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology	Seoul
Korea, Republic of	Yonsei Uni College of Medicine, Severance Hospital; Internal Medicine Dept.	Seoul
Latvia	Daugavpils Regional Hospital	Daugavpils
Latvia	P.Stradins Clinical University Hospital, Oncology Centre	Riga
Latvia	Rigas Austrumu Kliniska Universitates slimnica, Latvijas Onkologijas centrs	Riga
Mexico	Hospital Angeles Metropolitano; Room 220	Mexico City	Mexico CITY (federal District)
Mexico	Centro Oncologico Estatal ISSEMYM	Toluca
North Macedonia	Clinical Hospital; Oncology Department	Bitola
North Macedonia	Institute of Radiotherapy Oncology	Skopje
North Macedonia	Private Health Organization Acibadem Sistina Hospital	Skopje
Philippines	Cebu Cancer Institute; Perpetual Succour Hospital	Cebu City
Philippines	St Luke'S Medical Centre; Oncology	Quezon City
Philippines	Veterans Memorial Medical Center; Oncology	Quezon City
Poland	COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej	Lublin
Poland	Samodzielny Publiczny Kliniczny Nr 1 W Lublinie; Klinika Chirurgii Onkologicznej	Lublin
Poland	Oddzial Chemioterapii Szpitala Klinicznego Nr 1 w Poznaniu	Poznan
Poland	Zachodniopomorskie Centrum Onkologii, Osrodek Innowacyjnosci, Rozwoju i Badan Klinicznych	Szczecin
Poland	Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii	Warszawa
Russian Federation	Ivanovo Regional Oncology Dispensary	Ivanovo
Russian Federation	Regional Oncology Hospital Of Kursk; Chemotherapy	Kislino, Kursk Region
Russian Federation	Blokhin Cancer Research Center; Combined Treatment	Moscow
Russian Federation	Russian Oncology Research Center n.a. N.N. Blokhin Dpt of Clinical Pharmacology and Chemotherapy	Moscow
Russian Federation	Omsk Region Clinical Oncology Dispensary; 1St Sergical Department	Omsk
Russian Federation	State Inst. Of Healthcare Orenburg Regional Clinical Oncology Dis	Orenburg
Russian Federation	SBI of Healthcare Samara Regional Clinical Oncology Dispensary	Samara
Russian Federation	FSBI"National Medical Research Center of Oncology named after N.N.Petrov" MHRF	St Petersburg	Leningrad
Russian Federation	SBI of Healthcare Leningrad Regional Oncology Dispensary	St Petersburg
Singapore	National Cancer Centre; Medical Oncology	Singapore
Singapore	National University Hospital; National University Cancer Institute, Singapore (NCIS)	Singapore
Spain	Hospital Duran i Reynals; Oncologia	Barcelona
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona
Spain	Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia	Jaen
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología	La Coruña
Spain	Hospital Universitario de Canarias;servicio de Oncologia	La Laguna	Tenerife
Spain	Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia	Lerida
Spain	Centro Oncologico MD Anderson Internacional; Servicio de Oncologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga
Thailand	Chulalongkorn Hospital; Medical Oncology	Bangkok
Thailand	Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology	Bangkok
Thailand	National Cancer Inst.	Bangkok
Thailand	Rajavithi Hospital; Division of Medical Oncology	Bangkok
Thailand	Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc	Bangkok
Thailand	Songklanagarind Hospital; Department of Oncology	Songkhla
United Kingdom	Broomfield Hospital; Oncology	Chelmsford
United Kingdom	St James Uni Hospital; Icrf Cancer Medicine Research Unit	Leeds
United Kingdom	Leicester Royal Infirmary; Dept. of Medical Oncology	Leicester
United Kingdom	Charing Cross Hospital; Medical Oncology.	London
United Kingdom	Royal Free Hospital; Dept of Oncology	London
United Kingdom	St George'S Hospital; Oncology Research Office /Oncology Opd	London
United Kingdom	St. Bartholomew'S Hospital; Dept of Medical Oncology	London
United Kingdom	Mount Vernon Hospital; Centre For Cancer Treatment	Northwood
United Kingdom	Royal Cornwall Hospital; Dept of Clinical Oncology	Truro
United Kingdom	Southend Hospital; Oncology Dept	Westcliffe-on-sea
United Kingdom	The Clatterbridge Cancer Ctr For Oncolgy	Wirral
United States	Central Hematology Oncology Medical Group Inc.	Alhambra	California
United States	Pacific Cancer Medical Center	Anaheim	California
United States	Comprehensive Blood/Cancer Ctr	Bakersfield	California
United States	Kaiser Permanente - Baldwin Park	Baldwin Park	California
United States	Private Practice- Carolyn Hendricks, MD	Bethesda	Maryland
United States	Tower Cancer Research Foundation	Beverly Hills	California
United States	St. Vincent Frontier Cancer Center	Billings	Montana
United States	Boca Raton Comprehensive Cancer Center	Boca Raton	Florida
United States	Boston Medical Center	Boston	Massachusetts
United States	Wellmonth Physician Services	Bristol	Virginia
United States	Brockport-Interlakes Foundation	Brockport	New York
United States	South Bay Oncology Hematology Partners	Campbell	California
United States	Canandaigua-Interlakes Found	Canandaigua	New York
United States	Gabrail Cancer Center	Canton	Ohio
United States	Florida Cancer Specialists - Cape Coral (Del Prado Blvd)	Cape Coral	Florida
United States	Florida Cancer Specialists -Cape Coral (Cape Coral Pkwy)	Cape Coral	Florida
United States	Erlanger Health System; Oncology Research	Chattanooga	Tennessee
United States	SCRI Tennessee Oncology Chattanooga	Chattanooga	Tennessee
United States	Oncology Hematology Care Inc	Cincinnati	Ohio
United States	Hema Onc Conslts-Grant Ave	Columbus	Ohio
United States	Hematology Onc Consultants	Columbus	Ohio
United States	The Mark H. Zangmeister Ctr; Mid Ohio Onc/Hem Inc.	Columbus	Ohio
United States	Northwest Oncology/ Hematology Assoc.	Coral Springs	Florida
United States	Wilshire Oncology Medical Group	Corona	California
United States	Cons in Med Onc and Hem	Darby	Pennsylvania
United States	UM Sylvester Deerfield Beach; Sylvester Cancer Ctr	Deerfield Beach	Florida
United States	Gabrail Cancer Center	Dover	Ohio
United States	Consultants in Medical Oncology/Hematology	Drexel Hill	Pennsylvania
United States	Duke University Medical Center	Durham	North Carolina
United States	Southdale Cancer Clinic U of M Medical Center, Fairview- Edina	Edina	Minnesota
United States	Elmhurst Hospital	Elmhurst	Illinois
United States	Florida Cancer Specialists - Englewood	Englewood	Florida
United States	San Juan Oncology Associates	Farmington	New Mexico
United States	Florida Cancer Specialists - Broadway	Fort Myers	Florida
United States	Florida Cancer Specialists - Fort Myers (New Hampshire Ct)	Fort Myers	Florida
United States	Florida Cancer Specialists-Broadway, Fort Myers	Fort Myers	Florida
United States	Florida Cancer Specialists; SCRI	Fort Myers	Florida
United States	Compassionate Cancer Care	Fountain Valley	California
United States	Pacific Coast Hematology/Oncology Medical Group	Fountain Valley	California
United States	St. Jude Heritage Healthcare; Virgiia K.Crosson Can Ctr	Fullerton	California
United States	Northeast Georgia Medical Center; Oncology Research Dept-5C	Gainesville	Georgia
United States	Private Practice Robert R. Carroll, Md, Pa	Gainesville	Florida
United States	Geneva-Interlakes Foundation	Geneva	New York
United States	Wilshire Onc Med Grp., Inc	Glendora	California
United States	Cancer & Hematology Center of West Michigan	Grand Rapids	Michigan
United States	Cancer & Hematology Centers of Western Michigan	Grand Rapids	Michigan
United States	Hematology Oncology Consultants (NWK)	Granville	Ohio
United States	Carolina Oncology Specialists, PA - Hickory	Hickory	North Carolina
United States	Monroe Medical Associates - Hobart	Hobart	Indiana
United States	St. Mary Medical Center	Hobart	Indiana
United States	Memorial Cancer Institute	Hollywood	Florida
United States	Memorial Regional Hospital	Hollywood	Florida
United States	Memorial City-Main Office	Houston	Texas
United States	Oncology Consultants	Houston	Texas
United States	Park Plaza	Houston	Texas
United States	Southwest	Houston	Texas
United States	St. Joseph's	Houston	Texas
United States	St. Luke's	Houston	Texas
United States	Willowbrook	Houston	Texas
United States	Carolina BioOncology Institute, PLCC	Huntersville	North Carolina
United States	Hematology-Oncology of Indiana, Pc	Indianapolis	Indiana
United States	Uni of Iowa Hospital&Clinic; Holden Comprehens. Cancer Ctr	Iowa City	Iowa
United States	McLeod Cancer and Blood Center	Johnson City	Tennessee
United States	NEA Baptist Clinic	Jonesboro	Arkansas
United States	Katy-Christus St. Catherine	Katy	Texas
United States	Armstrong County Memorial Hospital	Kittanning	Pennsylvania
United States	University of Tennessee Cancer Institute;Hem-Onc Consultants	Knoxville	Tennessee
United States	Wilshire Oncology Medical Group	La Verne	California
United States	Cancer Center of Acadiana at Lafayette General	Lafayette	Louisiana
United States	ProHEALTH Care Associates LLP	Lake Success	New York
United States	Lakeland Regional Cancer Center	Lakeland	Florida
United States	Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	NW Carolina Onc & Hem	Lenoir	North Carolina
United States	Southeast Nebraska Cancer Center;; Southeast Nebraska Hematology and Oncology	Lincoln	Nebraska
United States	St. Barnabas Cancer Center	Livingston	New Jersey
United States	Cedars- Sinai Medical Center	Los Angeles	California
United States	LAC USC Medical Center	Los Angeles	California
United States	Ronald Reagan UCLA Medical Center Clin Lab	Los Angeles	California
United States	TORI Central Administration	Los Angeles	California
United States	UCLA	Los Angeles	California
United States	UCLA Hematology / Oncology Clinic	Los Angeles	California
United States	UCLA Med Ctr; Pharma Svcs	Los Angeles	California
United States	Jewish Cancer Care	Louisville	Kentucky
United States	Central Georgia Hematology Oncology Associates	Macon	Georgia
United States	Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital	Marietta	Georgia
United States	Jackson Memorial Hospital	Miami	Florida
United States	University of Miami School of Medicine	Miami	Florida
United States	Minneapolis Oncology Hamatology PA	Minneapolis	Minnesota
United States	US Oncology Research at Minnesota Oncology	Minneapolis	Minnesota
United States	Sutter Gould Medical Foundation; Clinical Research	Modesto	California
United States	Oncology and Hematology Specialists	Mountain Lakes	New Jersey
United States	Community Hospital; Pharmacy	Munster	Indiana
United States	Monroe Medical Associates	Munster	Indiana
United States	Northwest Oncology	Munster	Indiana
United States	Hematology Oncology Consultants Ltd	Naperville	Illinois
United States	Florida Cancer Specialists - Goodlette, Naples	Naples	Florida
United States	Florida Cancer Specialists - Pine Ridge, Naples	Naples	Florida
United States	Sarah Cannon Cancer Center - Tennessee Oncology, Pllc	Nashville	Tennessee
United States	The Jones Clinic, PC	New Albany	Mississippi
United States	Beth Israel Comprehensive Cancer Center Pharmacy	New York	New York
United States	The Women'sOncology & Wellness Practice	New York	New York
United States	Conslts in Med Onc (Newtown); Bryn Mawr Health Canc Ctr	Newtown Square	Pennsylvania
United States	Norfolk Oncology Consultants	Norfolk	Nebraska
United States	Kaiser Permanente - Oakland	Oakland	California
United States	Northern Utah Associates	Ogden	Utah
United States	Mercy Physicians of Oklahoma	Oklahoma City	Oklahoma
United States	Hematology-Oncology Consultants, Pc	Omaha	Nebraska
United States	Private Practice	Orlando	Florida
United States	Ventura County Hematology-Oncology Specialists	Oxnard	California
United States	UCLA Healthcare/Pasadena Oncology	Pasadena	California
United States	Wilshire Oncology Medical Group	Pasadena	California
United States	Breast Cancer Centre at Memorial Hospital West	Pembroke Pines	Florida
United States	Uni of Pittsburgh; Magee-Women'S Hospital	Pittsburgh	Pennsylvania
United States	Berkshire Hematology, Oncology Pc	Pittsfield	Massachusetts
United States	Bay Area Cancer Research Group, LLC	Pleasant Hill	California
United States	Wilshire Oncology Medical Group	Pomona	California
United States	Florida Cancer Specialists - Port Charlotte	Port Charlotte	Florida
United States	Quincy Medical Group	Quincy	Illinois
United States	Wilshire Oncology Medical Group	Rancho Cucamonga	California
United States	Consultants Med Onc & Hem	Ridley Park	Pennsylvania
United States	Upstate Ny Cancer Research & Education Foundation	Rochester	New York
United States	Community Cancer Center Rutland Regional Medical Center	Rutland	Vermont
United States	UC Davis Cancer Center; Oncology	Sacramento	California
United States	Oncology Care Associates PLLC	Saint Joseph	Michigan
United States	South Texas Oncology Hematology	San Antonio	Texas
United States	Kaiser Permanente San Diego; Hepatology Research	San Diego	California
United States	K. Permanente - San Fransisco	San Francisco	California
United States	K. Permanente - San Jose	San Jose	California
United States	Sansum Santa Barbara Medical Foundation Clinic	Santa Barbara	California
United States	Santa Barbara Hematology Oncology Medical Group, Inc.	Santa Barbara	California
United States	UCLA Hematology/Oncology	Santa Monica	California
United States	Florida Cancer Specialists; Sarasota	Sarasota	Florida
United States	HonorHealth Research Institute - Bisgrove	Scottsdale	Arizona
United States	Christus Schumpert Health System	Shreveport	Louisiana
United States	Oncology Consultants - Sugar Land	Sugar Land	Texas
United States	Northwest Medical Specialties	Tacoma	Washington
United States	Bay Area Oncology	Tampa	Florida
United States	Medical College of Ohio; Cancer Institute	Toledo	Ohio
United States	CA Care Associates-OK Oncology and Hematology	Tulsa	Oklahoma
United States	Cancer Care Assoc-S. Ingo	Tulsa	Oklahoma
United States	OK Oncology & Hematology PC	Tulsa	Oklahoma
United States	UCLA / Santa Clarita Valley Cancer Center	Valencia	California
United States	Kaiser Permanente - Vallejo	Vallejo	California
United States	Florida Cancer Specialists - Sunset Lake, Venice	Venice	Florida
United States	Florida Cancer Specialists - Venice (S. Tamiami Tr)	Venice	Florida
United States	Family Medicine Vincennes	Vincennes	Indiana
United States	St. Mary Medical Center	Walla Walla	Washington
United States	K. Permanente - Walnut Creek	Walnut Creek	California
United States	Central GA Cancer Care	Warner Robins	Georgia
United States	Georgetown University Medical Center Lombardi Cancer Center	Washington	District of Columbia
United States	MedStar Washington Hosp Center	Washington	District of Columbia
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	Wilshire Oncology Medical Group	West Covina	California
United States	Cleveland Clinic Florida	Weston	Florida
United States	University of Kansas; Medical Center & Medical pavilion	Westwood	Kansas
United States	Innovative clinical research institute/American institute of research	Whittier	California
United States	Cancer Center of Kansas	Wichita	Kansas
United States	Midwestern Regional Medical Center; Office of Research	Zion	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Genentech, Inc.	Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  China,  Costa Rica,  Croatia,  Ecuador,  Finland,  France,  Germany,  Guatemala,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Latvia,  Mexico,  North Macedonia,  Philippines,  Poland,  Russian Federation,  Singapore,  Spain,  Thailand,  United Kingdom, 

References & Publications (1)

Baselga J, Cortés 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 1 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) Determined by an Independent Review Facility	PFS was defined as the time from randomization to first documented radiographical progressive disease (PD), as determined by an independent review facility (IRF) using RECIST version 1.0, or death from any cause (within 18 weeks of last tumor assessment), whichever occurred first (Kaplan-Meier method). For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum of the LD recorded since treatment started or the appearance of =1 new lesion. For non-target lesions, PD was defined as the appearance of =1 new lesion or unequivocal progression of existing lesions. Participants without IRF-determined PD or who had not died within 18 weeks of their last IRF-determined, progression-free tumor assessment were censored at the date of the last IRF-reviewed, evaluable tumor assessment; those with no post-baseline tumor assessment and who had not died within 18 weeks of baseline were censored at 1 day.	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	Overall Survival	Overall survival (OS) was the time from randomization to death from any cause, using Kaplan-Meier methodology. Survival data was collected every 18 weeks during the post-treatment follow-up period until death, loss to follow-up, or withdrawal of consent. Those who were alive, lost to follow up, or withdrew consent were censored at the latest date they participated in the study; those without post-baseline data were censored at 1 day. OS analyses were planned to take place at the primary completion date (First Interim), after 385 deaths (Event-Driven Final), and at the end of study (End-of-Study). A second interim OS analysis was planned due to a formal request from the European Medicines Agency. Median [range] time in weeks on study at each OS analysis (Pertuzumab vs. Placebo): First: 77.1 [0.7-165.3] vs. 73.1 [0.4-165.3]; Second: 117.1 [0.7-207.9] vs. 105.9 [0.4-207.9]; Event-Driven Final: 189.9 [0.7-304.1] vs. 140.5 [0.4-301.6]; End-of-Study: 201.8 [0.7-520.0] vs. 138.0 [0.4-514.7].	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)
Secondary	Progression-Free Survival (PFS) Determined by the Investigator	PFS was defined as the time from randomization to first documented radiographical progressive disease (PD), as determined by the investigator using RECIST version 1.0, or death from any cause (within 18 weeks of last tumor assessment), whichever occurred first (Kaplan-Meier method). For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum of the LD recorded since treatment started or the appearance of =1 new lesion. For non-target lesions, PD was defined as the appearance of =1 new lesion or unequivocal progression of existing lesions. Participants without PD or who had not died within 18 weeks of their last investigator-determined, progression-free tumor assessment were censored at the date of the last investigator tumor assessment; those with no post-baseline tumor assessment and who had not died within 18 weeks of baseline were censored at 1 day.	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)
Secondary	Objective Response Determined by an Independent Review Facility	An objective response was defined as the percentage of participants with confirmed best overall response of complete response (CR) or partial response (PR) determined by an independent review facility (IRF) using RECIST v1.0 on two consecutive occasions =4 weeks apart. For target lesions, CR: disappearance of all target lesions; PR: =30% decrease in the sum of the longest diameter (LD) of target lesions (baseline sum LD as reference); PD: =20% increase in the sum of the LD of target lesions (smallest sum of the LD recorded as reference) or appearance of =1 new lesion; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase for PD. For non-target lesions, CR: disappearance of all non-target lesions; Incomplete/SD: persistence of =1 non-target lesions; PD: unequivocal progression of existing non-target lesions. 95% confidence intervals (CI) were calculated only for clinical responses using the Pearson-Clopper method.	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)
Secondary	Duration of Objective Response Determined by an Independent Review Facility	Duration of objective response (estimated using the Kaplan-Meier method) was defined as the time from the initial confirmed complete response (CR) or partial response (PR), the date of tumor assessment at which the CR/PR was first detected by the independent review facility (IRF) using RECIST version 1.0, until the date of IRF-determined progressive disease (PD), death from any cause within 18 weeks of the last tumor assessment, or first administration of next line of anti-cancer therapy (whichever occurred first). If the visit when the initial CR or PR was observed spanned multiple dates, the latest date was used. Only participants in the ITT analysis population with an IRF-determined objective response (CR or PR), observed prior to IRF-assessed PD, death or next line of anti-cancer therapy, were included in the analysis. Participants who did not progress or die after they had a confirmed response were censored at the date of their last IRF-evaluable tumor measurement.	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)
Secondary	Time to Symptom Progression	Time to symptom progression was defined as the time from randomization to the first symptom progression as measured by the Functional Assessment of Cancer Therapy-for patients with Breast Cancer (FACT-B) questionnaire with the Trial Outcomes Index-Physical/Functional/Breast (TOI-PFB) subscale. The FACT-B TOI-PFB subscale contains 24 items from 3 subsections of the FACT-B questionnaire: Physical well-being, functional well-being, and additional concerns for breast cancer patients (breast cancer subscale [BCS]). All items in the questionnaire were rated by the patient on a 5-point scale ranging from 0 ("not at all") to 4 ("very much"). The total score ranged from 0 to 96. A higher score indicates better perceived quality of life. A positive change score from baseline indicates improvement. Symptom progression was defined as a decrease from baseline of 5 points or more.	Every 9 weeks from Baseline until investigator-determined progressive disease, up to the primary completion date (up to 3 years, 3 months)
Secondary	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	Adverse event (AE) severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 (NCI-CTCAE v3.0); if the AE was not specifically listed, the following grades of severity were used: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening or disabling; and Grade 5 = death. Severe and serious are not synonymous. Severity refers to the intensity of an AE, whereas a serious AE must meet criteria set out in the protocol; both were independently assessed for each AE. Only the most severe intensity was counted for multiple occurrences of the same AE in one participant. AEs reported prior to first crossover treatment were included in the Placebo arm, and in the Crossover arm after that date, for participants who crossed over from placebo to pertuzumab. Median [range] time on study treatment per arm: Placebo: 49.3 [0.3-514.7] weeks; Pertuzumab: 75.7 [0.6-519.6] weeks; Crossover: 129.9 [0.3-322.3] weeks.	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)
Secondary	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	Adverse event (AE) severity, including serious and non-serious AEs, was assessed according to the NCI-CTCAE version 3.0; if the AE was not specifically listed, the following grades of severity were used: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe; Grade 4 is life-threatening or disabling; and Grade 5 is death. Multiple occurrences of the same AE in 1 participant were counted multiple times. Only AEs that started during the overall study treatment period were included. The cutoff date for inclusion of events and for calculation of patient-years was the date of the most recent follow-up of the participant, defined as the last available date during the treatment period, excluding pre-treatment and safety follow-up data. Confidence intervals were calculated assuming the number of events followed a Poisson distribution. Data reported prior to the date of first crossover treatment were included under the Placebo arm for participants who crossed over from placebo to pertuzumab.	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)
Secondary	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	Cardiac-related adverse events (AEs) to monitor during the study included investigator-assessed symptomatic left ventricular dysfunction (LVD), any LVD, or a serious adverse event (SAE) suggestive of congestive heart failure (CHF). All cardiac-related AEs were graded for severity according to NCI-CTCAE v3.0. Asymptomatic (Grades 1-2) and symptomatic (Grades 3-5) left ventricular systolic dysfunction (LVSD) both coded to the MedDRA preferred term LVD. Investigator-assessed events of symptomatic LVD were also graded for severity of symptoms according to Classes I (least severe) to IV (most severe) of the New York Heart Association (NYHA) Classification. SAEs suggestive of CHF were identified as serious events from the Standardized MedDRA Query (SMQ) (Wide) 'Cardiac Failure'. Median [range] time on study treatment per arm: Placebo: 49.3 [0.3-514.7] weeks; Pertuzumab: 75.7 [0.6-519.6] weeks; Crossover: 129.9 [0.3-322.3] weeks.	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)
Secondary	Number of Participants Who Experienced at Least One Adverse Event to Monitor (Excluding Cardiac-Related AEs) by Severity During the Treatment Period	The clinical diagnoses listed in this table, excluding cardiac safety (summarized separately), were also selected as adverse events (AEs) to monitor based on clinical and nonclinical data for pertuzumab and the safety profile established for trastuzumab, monoclonal antibodies in general, and potential effects associated with HER receptor inhibition. Search strategies were defined by single or aggregate MedDRA Preferred Terms (PT) through Standardized MedDRA Queries (SMQ), where possible, or based on Roche AE Group Terms (AEGT). Diarrhoea AEs: High-Level Term (HLT) 'Diarrhoea (excl. infective)' and PT 'Diarrhoea infectious'. Leukopenic and Febrile Neutropenic Infections: AEs from 'Infections & Infestations' with start =14 days after start date of Grade =3 AEs in SMQ(narrow) 'Leukopenia' or PT 'Febrile neutropenia', respectively. Median [range] time on study treatment per arm: Placebo: 49.3 [0.3-514.7] weeks; Pertuzumab: 75.7 [0.6-519.6] weeks; Crossover: 129.9 [0.3-322.3] weeks.	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)
Secondary	Overall Number of Participants Who Experienced at Least One Adverse Event Leading to Discontinuation of Any or All Study Medication	Participants could continue study treatment with pertuzumab/placebo plus trastuzumab when docetaxel was discontinued due to an adverse event (AE). Discontinuation of pertuzumab/placebo or trastuzumab due to an AE led to discontinuation of all study medication. The number of participants who discontinued any study medication due to an AE includes those who discontinued all study medication and those who discontinued docetaxel only and then continued on targeted therapy (note: some of these participants may have subsequently discontinued all treatment due to a separate AE). Multiple occurrences of the same adverse event in 1 participant was counted only once. AEs reported prior to first crossover treatment were included in the Placebo arm, and after that date in the Crossover arm, for those who crossed over from placebo to pertuzumab. Median [range] time on study treatment per arm: Placebo: 49.3 [0.3-514.7] weeks; Pertuzumab: 75.7 [0.6-519.6] weeks; Crossover: 129.9 [0.3-322.3] weeks.	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)
Secondary	Overall Number of Participants Who Experienced at Least One Adverse Event That Resulted in Interruption or Modification of Any Study Medication	Pertuzumab, trastuzumab, and docetaxel administration could have been delayed to assess or treat adverse events (AEs). Docetaxel dose reduction was allowed for myelosuppression, hepatic dysfunction, and other toxicities. No dose reduction was allowed for pertuzumab or trastuzumab. Multiple occurrences of the same adverse event in one participant was counted only once. AEs reported prior to first crossover treatment were included in the Placebo arm, and after that date in the Crossover arm, for participants who crossed over from placebo to pertuzumab. Median [range] time on study treatment per arm: Placebo: 49.3 [0.3-514.7] weeks; Pertuzumab: 75.7 [0.6-519.6] weeks; Crossover: 129.9 [0.3-322.3] weeks	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)
Secondary	Number of Participants Who Experienced at Least One Adverse Event During the Post-Treatment Follow-Up Period	The post-treatment period was defined as the period following the treatment discontinuation visit. Only the following new adverse events (AEs) should have been reported during the post-treatment follow-up period: 1. Cardiac events (regardless of causality or seriousness) that started up to 1 year after the last dose, except for symptomatic left ventricular systolic dysfunction (regardless of causality) that started up to 3 years after the last dose; and 2. Treatment-related serious AEs, regardless of start date. AEs are listed by Medical Dictionary for Regulatory Activities, Version 21.1 (MedDRA v21.1) System Organ Class (SOC) and Preferred Term (PT); PTs fall under the SOC that is listed immediately above it in the table. Multiple occurrences of the same AE in one participant was counted only once. AEs reported prior to first crossover treatment were included in the Placebo arm, and after that date in the Crossover arm, for participants who crossed over from placebo to pertuzumab.	From Day 43 after discontinuation of all study medication to end of post-treatment follow-up period (up to 3 years)
Secondary	Number of Participants by Categories for the Maximum Absolute Decrease From Baseline in LVEF Value During the Treatment Period	All participants were required to have an left ventricular ejection fraction (LVEF) =50% at baseline, as measured by echocardiogram (preferred) or multiple-gated acquisition (MUGA) scan. The same method of LVEF assessment and the same institution/facility used at baseline was used throughout the study, to the extent possible. The baseline value was defined as the last valid value recorded during the pre-treatment period before or on study Day 1. The maximum absolute decrease in LVEF value was defined as the lowest post-baseline value up to the end of the overall study treatment period. Data reported prior to first crossover treatment were included in the Placebo arm, and after that date in the Crossover arm, for participants who crossed over from placebo to pertuzumab. Median [range] time on study treatment per arm: Placebo: 49.3 [0.3-514.7] weeks; Pertuzumab: 75.7 [0.6-519.6] weeks; Crossover: 129.9 [0.3-322.3] weeks.	Every 9 weeks from the date of randomization until Treatment Discontinuation Visit (see Description for time on study treatment per arm)
Secondary	Baseline LVEF Value and Change in LVEF From Baseline at Maximum Absolute Decrease Value During the Treatment Period	All participants were required to have a left ventricular ejection fraction (LVEF) =50% at baseline, as measured by echocardiogram (preferred) or multiple-gated acquisition (MUGA) scan. The same method of LVEF assessment and the same institution/facility used at baseline was used throughout the study, to the extent possible. The baseline value was defined as the last valid value recorded during the pre-treatment period before or on study Day 1. The maximum absolute decrease in LVEF value was defined as the lowest post-baseline value up to the end of the overall study treatment period. Only data reported prior to the date of first crossover treatment were included for participants who crossed over from placebo to pertuzumab.	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)
Secondary	Number of Participants With Laboratory Abnormalities in Blood Biochemistry Tests by Highest Grade According to NCI-CTCAE v3.0 During the Treatment Period	Clinical laboratory tests for blood biochemistry parameters were performed at local laboratories; any abnormal values (High or Low) were based on local laboratory normal ranges. Laboratory abnormalities are presented by the highest grade according to NCI-CTCAE v3.0. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy. Median [range] time on study treatment per arm: Placebo: 49.3 [0.3-514.7] weeks; Pertuzumab: 75.7 [0.6-519.6] weeks; Crossover: 129.9 [0.3-322.3] weeks. ALP = alkaline phosphatase; GGT = gamma-glutamyl transferase; SGOT = serum glutamic-oxaloacetic transaminase; SGPT = serum glutamic-pyruvic transaminase	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)
Secondary	Number of Participants With Laboratory Abnormalities in Hematology Tests by Highest Grade According to NCI-CTCAE v3.0 During the Treatment Period	Clinical laboratory tests for hematology parameters were performed at local laboratories; any abnormal values (High or Low) were based on local laboratory normal ranges. Laboratory abnormalities are presented by the highest grade according to NCI-CTCAE v3.0. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy. Median [range] time on study treatment per arm: Placebo: 49.3 [0.3-514.7] weeks; Pertuzumab: 75.7 [0.6-519.6] weeks; Crossover: 129.9 [0.3-322.3] weeks. INR = International Normalized Ratio; PTT = partial thromboplastin time; WBC = white blood cell	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)