AzTrials
AzTrials

Metastatic Breast CancerPhase 3CLEOPATRANCT00567190

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

A Phase 3 study testing Pertuzumab, Trastuzumab and Docetaxel in people with Metastatic Breast Cancer, run by Genentech, Inc. at 322 sites in 26 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
Pertuzumab, Trastuzumab and Docetaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
808 participants
Where
322 sitesin 26 countries
Study dates
12 Feb 2008to 23 Nov 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

322 sites in 26 countries.

322 sites in 26 countries

United States159 sites

  • Central Hematology Oncology Medical Group Inc.

    Alhambra, California, 91801

  • Pacific Cancer Medical Center

    Anaheim, California, 92801

  • Comprehensive Blood/Cancer Ctr

    Bakersfield, California, 93309

  • Kaiser Permanente - Baldwin Park

    Baldwin Park, California, 91706

  • Private Practice- Carolyn Hendricks, MD

    Bethesda, Maryland, 20817

  • Tower Cancer Research Foundation

    Beverly Hills, California, 90211

  • St. Vincent Frontier Cancer Center

    Billings, Montana, 59101

  • Boca Raton Comprehensive Cancer Center

    Boca Raton, Florida, 33428

  • Boston Medical Center

    Boston, Massachusetts, 02118-2393

  • Wellmonth Physician Services

    Bristol, Virginia, 24201

  • Brockport-Interlakes Foundation

    Brockport, New York, 14420

  • South Bay Oncology Hematology Partners

    Campbell, California, 95008

  • Canandaigua-Interlakes Found

    Canandaigua, New York, 14420

  • Gabrail Cancer Center

    Canton, Ohio, 44718

  • Florida Cancer Specialists -Cape Coral (Cape Coral Pkwy)

    Cape Coral, Florida, 33914

  • Florida Cancer Specialists - Cape Coral (Del Prado Blvd)

    Cape Coral, Florida, 33990

  • Erlanger Health System; Oncology Research

    Chattanooga, Tennessee, 37403

  • SCRI Tennessee Oncology Chattanooga

    Chattanooga, Tennessee, 37404

  • Oncology Hematology Care Inc

    Cincinnati, Ohio, 45242

  • Hema Onc Conslts-Grant Ave

    Columbus, Ohio, 43215

  • The Mark H. Zangmeister Ctr; Mid Ohio Onc/Hem Inc.

    Columbus, Ohio, 43219

  • Hematology Onc Consultants

    Columbus, Ohio, 43228

  • Northwest Oncology/ Hematology Assoc.

    Coral Springs, Florida, 33065-5701

  • Wilshire Oncology Medical Group

    Corona, California, 92879

  • Cons in Med Onc and Hem

    Darby, Pennsylvania, 19026

  • UM Sylvester Deerfield Beach; Sylvester Cancer Ctr

    Deerfield Beach, Florida, 33442

  • Gabrail Cancer Center

    Dover, Ohio, 44622

  • Consultants in Medical Oncology/Hematology

    Drexel Hill, Pennsylvania, 19026

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Southdale Cancer Clinic U of M Medical Center, Fairview- Edina

    Edina, Minnesota, 55435

  • Elmhurst Hospital

    Elmhurst, Illinois, 60126

  • Florida Cancer Specialists - Englewood

    Englewood, Florida, 34223

  • San Juan Oncology Associates

    Farmington, New Mexico, 87401

  • Florida Cancer Specialists - Fort Myers (New Hampshire Ct)

    Fort Myers, Florida, 33901-8101

  • Florida Cancer Specialists - Broadway

    Fort Myers, Florida, 33901

  • Florida Cancer Specialists; SCRI

    Fort Myers, Florida, 33901

  • Florida Cancer Specialists-Broadway, Fort Myers

    Fort Myers, Florida, 33908

  • Compassionate Cancer Care

    Fountain Valley, California, 92708

  • Pacific Coast Hematology/Oncology Medical Group

    Fountain Valley, California, 92708

  • St. Jude Heritage Healthcare; Virgiia K.Crosson Can Ctr

    Fullerton, California, 92835

  • Private Practice Robert R. Carroll, Md, Pa

    Gainesville, Florida, 32605

  • Northeast Georgia Medical Center; Oncology Research Dept-5C

    Gainesville, Georgia, 30501

  • Geneva-Interlakes Foundation

    Geneva, New York, 14456

  • Wilshire Onc Med Grp., Inc

    Glendora, California, 91741

  • Cancer & Hematology Centers of Western Michigan

    Grand Rapids, Michigan, 49503

  • Cancer & Hematology Center of West Michigan

    Grand Rapids, Michigan, 49546

  • Hematology Oncology Consultants (NWK)

    Granville, Ohio, 43023

  • Carolina Oncology Specialists, PA - Hickory

    Hickory, North Carolina, 28602

  • Monroe Medical Associates - Hobart

    Hobart, Indiana, 46342

  • St. Mary Medical Center

    Hobart, Indiana, 46432

  • Memorial Cancer Institute

    Hollywood, Florida, 33021

  • Memorial Regional Hospital

    Hollywood, Florida, 33021

  • Park Plaza

    Houston, Texas, 77004

  • Southwest

    Houston, Texas, 77008

  • St. Joseph's

    Houston, Texas, 77008

  • Memorial City-Main Office

    Houston, Texas, 77024

  • Oncology Consultants

    Houston, Texas, 77024

  • St. Luke's

    Houston, Texas, 77030

  • Willowbrook

    Houston, Texas, 77070

  • Carolina BioOncology Institute, PLCC

    Huntersville, North Carolina, 28078

  • Hematology-Oncology of Indiana, Pc

    Indianapolis, Indiana, 46260

  • Uni of Iowa Hospital&Clinic; Holden Comprehens. Cancer Ctr

    Iowa City, Iowa, 52242

  • McLeod Cancer and Blood Center

    Johnson City, Tennessee, 37604

  • NEA Baptist Clinic

    Jonesboro, Arkansas, 72401

  • Katy-Christus St. Catherine

    Katy, Texas, 77450

  • Armstrong County Memorial Hospital

    Kittanning, Pennsylvania, 16201

  • University of Tennessee Cancer Institute;Hem-Onc Consultants

    Knoxville, Tennessee, 37920

  • Wilshire Oncology Medical Group

    La Verne, California, 91750

  • Cancer Center of Acadiana at Lafayette General

    Lafayette, Louisiana, 70506

  • ProHEALTH Care Associates LLP

    Lake Success, New York, 11042

  • Lakeland Regional Cancer Center

    Lakeland, Florida, 33804-1057

  • Southern Nevada Cancer Research Foundation

    Las Vegas, Nevada, 89106

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • NW Carolina Onc & Hem

    Lenoir, North Carolina, 28645

  • Southeast Nebraska Cancer Center;; Southeast Nebraska Hematology and Oncology

    Lincoln, Nebraska, 68510

  • St. Barnabas Cancer Center

    Livingston, New Jersey, 07039

  • UCLA

    Los Angeles, California, 90024

  • LAC USC Medical Center

    Los Angeles, California, 90033

  • Cedars- Sinai Medical Center

    Los Angeles, California, 90048

  • Ronald Reagan UCLA Medical Center Clin Lab

    Los Angeles, California, 90095

  • TORI Central Administration

    Los Angeles, California, 90095

  • UCLA Hematology / Oncology Clinic

    Los Angeles, California, 90095

  • UCLA Med Ctr; Pharma Svcs

    Los Angeles, California, 90095

  • Jewish Cancer Care

    Louisville, Kentucky, 40245

  • Central Georgia Hematology Oncology Associates

    Macon, Georgia, 31201

  • Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital

    Marietta, Georgia, 30060

  • Jackson Memorial Hospital

    Miami, Florida, 33136

  • University of Miami School of Medicine

    Miami, Florida, 33136

  • US Oncology Research at Minnesota Oncology

    Minneapolis, Minnesota, 55404

  • Minneapolis Oncology Hamatology PA

    Minneapolis, Minnesota, 55407-3799

  • Sutter Gould Medical Foundation; Clinical Research

    Modesto, California, 95355

  • Oncology and Hematology Specialists

    Mountain Lakes, New Jersey, 07046

  • Community Hospital; Pharmacy

    Munster, Indiana, 46321

  • Northwest Oncology

    Munster, Indiana, 46321

  • Monroe Medical Associates

    Munster, Indiana, 46375

  • Hematology Oncology Consultants Ltd

    Naperville, Illinois, 60540

  • Florida Cancer Specialists - Goodlette, Naples

    Naples, Florida, 34102

  • Florida Cancer Specialists - Pine Ridge, Naples

    Naples, Florida, 34119

  • Sarah Cannon Cancer Center - Tennessee Oncology, Pllc

    Nashville, Tennessee, 37203

  • The Jones Clinic, PC

    New Albany, Mississippi, 38652

  • Beth Israel Comprehensive Cancer Center Pharmacy

    New York, New York, 10011

  • The Women'sOncology & Wellness Practice

    New York, New York, 10016

  • Conslts in Med Onc (Newtown); Bryn Mawr Health Canc Ctr

    Newtown Square, Pennsylvania, 19073

  • Norfolk Oncology Consultants

    Norfolk, Nebraska, 68701

  • Kaiser Permanente - Oakland

    Oakland, California, 94611

  • Northern Utah Associates

    Ogden, Utah, 84403

  • Mercy Physicians of Oklahoma

    Oklahoma City, Oklahoma, 73120

  • Hematology-Oncology Consultants, Pc

    Omaha, Nebraska, 68122

  • Private Practice

    Orlando, Florida, 32804

  • Ventura County Hematology-Oncology Specialists

    Oxnard, California, 93030

  • UCLA Healthcare/Pasadena Oncology

    Pasadena, California, 91105

  • Wilshire Oncology Medical Group

    Pasadena, California, 91750

  • Breast Cancer Centre at Memorial Hospital West

    Pembroke Pines, Florida, 33028

  • Uni of Pittsburgh; Magee-Women'S Hospital

    Pittsburgh, Pennsylvania, 15213

  • Berkshire Hematology, Oncology Pc

    Pittsfield, Massachusetts, 01201

  • Bay Area Cancer Research Group, LLC

    Pleasant Hill, California, 94523

  • Wilshire Oncology Medical Group

    Pomona, California, 91767

  • Florida Cancer Specialists - Port Charlotte

    Port Charlotte, Florida, 33980

  • Quincy Medical Group

    Quincy, Illinois, 62301

  • Wilshire Oncology Medical Group

    Rancho Cucamonga, California, 91730

  • Consultants Med Onc & Hem

    Ridley Park, Pennsylvania, 19078

  • Upstate Ny Cancer Research & Education Foundation

    Rochester, New York, 14623

  • Community Cancer Center Rutland Regional Medical Center

    Rutland, Vermont, 05701

  • UC Davis Cancer Center; Oncology

    Sacramento, California, 95817

  • Oncology Care Associates PLLC

    Saint Joseph, Michigan, 49085

  • South Texas Oncology Hematology

    San Antonio, Texas, 78258

  • Kaiser Permanente San Diego; Hepatology Research

    San Diego, California, 92154

  • K. Permanente - San Fransisco

    San Francisco, California, 94115

  • K. Permanente - San Jose

    San Jose, California, 95119

  • Sansum Santa Barbara Medical Foundation Clinic

    Santa Barbara, California, 93105

  • Santa Barbara Hematology Oncology Medical Group, Inc.

    Santa Barbara, California, 93105

  • UCLA Hematology/Oncology

    Santa Monica, California, 90404

  • Florida Cancer Specialists; Sarasota

    Sarasota, Florida, 34232

  • HonorHealth Research Institute - Bisgrove

    Scottsdale, Arizona, 85258

  • Christus Schumpert Health System

    Shreveport, Louisiana, 71101-1978

  • Oncology Consultants - Sugar Land

    Sugar Land, Texas, 77479

  • Northwest Medical Specialties

    Tacoma, Washington, 98405

  • Bay Area Oncology

    Tampa, Florida, 33607

  • Medical College of Ohio; Cancer Institute

    Toledo, Ohio, 43614

  • CA Care Associates-OK Oncology and Hematology

    Tulsa, Oklahoma, 74104

  • Cancer Care Assoc-S. Ingo

    Tulsa, Oklahoma, 74133

  • OK Oncology & Hematology PC

    Tulsa, Oklahoma, 74136

  • UCLA / Santa Clarita Valley Cancer Center

    Valencia, California, 91355

  • Kaiser Permanente - Vallejo

    Vallejo, California, 94589

  • Florida Cancer Specialists - Venice (S. Tamiami Tr)

    Venice, Florida, 33980

  • Florida Cancer Specialists - Sunset Lake, Venice

    Venice, Florida, 34292

  • Family Medicine Vincennes

    Vincennes, Indiana, 47591

  • St. Mary Medical Center

    Walla Walla, Washington, 99362

  • K. Permanente - Walnut Creek

    Walnut Creek, California, 94596

  • Central GA Cancer Care

    Warner Robins, Georgia, 31088-2259

  • Georgetown University Medical Center Lombardi Cancer Center

    Washington D.C., District of Columbia, 20007

  • MedStar Washington Hosp Center

    Washington D.C., District of Columbia, 20010

  • Sibley Memorial Hospital

    Washington D.C., District of Columbia, 20016

  • Wilshire Oncology Medical Group

    West Covina, California, 91790

  • Cleveland Clinic Florida

    Weston, Florida, 33331

  • University of Kansas; Medical Center & Medical pavilion

    Westwood, Kansas, 66205

  • Innovative clinical research institute/American institute of research

    Whittier, California, 90603

  • Cancer Center of Kansas

    Wichita, Kansas, 67214-3728

  • Midwestern Regional Medical Center; Office of Research

    Zion, Illinois, 60099

Other trials in United States

Japan28 sites

  • Aichi Cancer Center Hospital, Breast Oncology

    Aichi, 464-8681

  • Chiba Cancer Center; Breast Surgical Oncology

    Chiba, 260-8717

  • National Cancer Center Hospital East; Breast and Medical Oncology

    Chiba, 277-8577

  • Natl Hosp Org Shikoku; Cancer Ctr, Surgery

    Ehime, 791-0280

  • Kitakyushu Municipal Medical Center, Surgery

    Fukuoka, 802-0077

  • National Hospital Organization Kyushu Cancer Center;Breast Oncology

    Fukuoka, 811-1395

  • Gunma University Hospital; Department of Thoracic and Visceral Organ Surgery

    Gunma, 371-8511

  • Sagara Hospital; Breast Surgery

    Kagoshima, 892-0833

  • St. Marianna University School of Medicine Hospital, Breast and Endocrine Surgery

    Kanagawa, 216-8511

  • Tokai University Hospital, Breast and Endocrine Surgery

    Kanagawa, 259-1193

  • Kumamoto City Hospital, Breast and Endocrine Surgery

    Kumamoto, 862-8505

  • Kumamoto Shinto General Hospital; Breast Cancer Center

    Kumamoto, 862-8655

  • Kyoto University Hospital; Breast Surgery

    Kyoto, 606-8507

  • Niigata Cancer Ctr Hospital; Breast Surgery

    Niigata, 951-8566

  • Iwate Med Univ School of Med; Surgery

    Numakunai, 020-8505

  • OSAKA CITY GENERAL HOSPITAL;Medical Oncology

    Osaka, 534-0021

  • National Hospital Organization Osaka National Hospital; Breast Surgery

    Osaka, 540-0006

  • Osaka University Hospital; Breast and Endocrine Surgery

    Osaka, 565-0871

  • Saitama Medical University International Medical Center; Medical Oncology

    Saitama, 350-1298

  • Saitama Cancer Center, Breast Oncology

    Saitama, 362-0806

  • Shizuoka Cancer Center; Female Internal Medicine

    Shizuoka, 411-8777

  • Shizuoka General Hospital; Breast Surgery

    Shizuoka, 420-8527

  • Jichi Medical University; Dept of Clinical Oncology

    Tochigi, 329-0498

  • National Cancer Center Hospital; Breast and Medical Oncology

    Tokyo, 104-0045

  • St. Luke's Internat. Hospital, Breast Surgical Oncology

    Tokyo, 104-8560

  • Tokyo Metropolitan; Komagome Hospital, Surgery

    Tokyo, 113-8677

  • The Cancer Inst. Hosp. of JFCR; Breast Oncology Center

    Tokyo, 135-8550

  • Tokyo Medical Uni. Hospital; Breast Oncology

    Tokyo, 160-0023

Other trials in Japan

Brazil19 sites

  • Crio - Centro Regional Integrado de Oncologia

    Fortaleza, Ceará, 60336-550

  • Centro Goiano de Oncologia - CGO

    Goiânia, Goiás, 74140-050

  • Hospital de Caridade de Ijui; Oncologia

    Ijuí, Rio Grande do Sul, 98700-000

  • Hospital Amaral Carvalho

    Jaú, São Paulo, 17210-120

  • Santa Casa de Misericordia de Porto Alegre

    Porto Alegre, Rio Grande do Sul, 90020-090

  • Hospital das Clinicas - UFRGS

    Porto Alegre, Rio Grande do Sul, 90035-903

  • Hospital Nossa Senhora da Conceicao

    Porto Alegre, Rio Grande do Sul, 91350-200

  • Hospital das Clinicas - FMUSP Ribeirao Preto

    Ribeirão Preto, São Paulo, 14048-900

  • Instituto Nacional de Cancer - INCa; Oncologia

    Rio de Janeiro, Rio de Janeiro, 20560-120

  • Hospital Universitario Clementino Fraga Filho - UFRJ; Oncologia

    Rio de Janeiro, Rio de Janeiro, 21941-590

  • Clinica Amo - Assistencia Medica Em Oncologia

    Salvador, Estado de Bahia, 41950-610

  • Faculdade de Medicina do ABC - FMABC; Oncologia e Hematologia

    Santo André, São Paulo, 09060-650

  • Iso - Inst. Santista de Oncologia

    Santos, São Paulo, 11075-350

  • Instituto do Cancer Arnaldo Vieira de Carvalho - ICAVC; Pesquisa Clinica

    São Paulo, São Paulo, 01221-020

  • Instituto do Cancer do Estado de Sao Paulo - ICESP

    São Paulo, São Paulo, 01246-000

  • Hospital Perola Byington

    São Paulo, São Paulo, 01317-000

  • Inst. Brasileiro de Controle Ao Cancer; Oncologia Clinica / Quimioterapia

    São Paulo, São Paulo, 03102-002

  • Hospital Estadual do Servidor Publico

    São Paulo, São Paulo, 04039-901

  • Instituto de Oncologia de Sorocaba - CEPOS

    Sorocaba, São Paulo, 18030-005

Other trials in Brazil

Germany13 sites

  • Onkologischer Schwerpunkt am Oskar-Helene-Heim; Dres. Herrenberger, Keitel-Wittig u. Kirsch

    Berlin, 14195

  • Onkologische Schwerpunktpraxis Bielefeld; Haemotologie & Internistische onkologie

    Bielefeld, 33604

  • St. Elisabeth Krankenhaus Köln GmbH; Gynäkologie und Geburtshilfe

    Cologne, 50935

  • Universitätsklinikum Essen; Zentrum Für Frauenheilkunde

    Essen, 45122

  • Universitätsklinikum Halle (Saale); Universitätsklinik Und Poliklinik Für Gynäkologie

    Halle, 06120

  • Universitätsklinikum Hamburg-Eppendorf; Frauenklinik

    Hamburg, 20246

  • Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg

    Heidelberg, 69120

  • Universitätsmedizin Mainz; Klinik u. Poliklinik f. Geburtshilfe u. Frauenheilkunde

    Mainz, 55131

  • Krankenhaus Rheinfelden; Frauenklinik

    Rheinfelden, 79618

  • Robert-Bosch-Krankenhaus; Hämatologie, Onkologie und Palliativmedizin

    Stuttgart, 70376

  • Klinikum Mutterhaus der Borromaeerinnen gGmbH; Haematologie/Onkologie

    Trier, 54290

  • Universitätsklinik Tübingen; Frauenklinik

    Tübingen, 72076

  • Haematologisch-Onkologische Praxis; Dr. med. Christoph Maintz und Matthias Groschek

    Würselen, 52146

Other trials in Germany

United Kingdom11 sites

  • Broomfield Hospital; Oncology

    Chelmsford, CM1 7ET

  • St James Uni Hospital; Icrf Cancer Medicine Research Unit

    Leeds, LS9 7TF

  • Leicester Royal Infirmary; Dept. of Medical Oncology

    Leicester, LE1 5WW

  • St. Bartholomew'S Hospital; Dept of Medical Oncology

    London, EC1A 7BE

  • Royal Free Hospital; Dept of Oncology

    London, NW3 2QG

  • St George'S Hospital; Oncology Research Office /Oncology Opd

    London, SW17 ORE

  • Charing Cross Hospital; Medical Oncology.

    London, W6 8RF

  • The Clatterbridge Cancer Ctr For Oncolgy

    Metropolitan Borough of Wirral, CH63 4JY

  • Mount Vernon Hospital; Centre For Cancer Treatment

    Northwood, HA6 2RN

  • Royal Cornwall Hospital; Dept of Clinical Oncology

    Truro, TR1 3LJ

  • Southend Hospital; Oncology Dept

    Westcliffe-on-sea, SS0 0RY

Other trials in United Kingdom

Italy10 sites

  • Azienda Sanitaria S. Maria Annunziata; S. C. Oncologia Medica

    Antella (FI), Tuscany, 50011

  • Az. Osp. Spedali Civili; Divisione Di Oncologia - Iii Medicina

    Brescia, Lombardy, 25123

  • Ospedale Antonio Perrino; Oncologia Medica

    Brindisi, Apulia, 72100

  • Fondazione Del Piemonte Per L'oncologia IRCC Di Candiolo

    Candiolo, Piedmont, 10060

  • Policlinico Ospedaliero Ss Annunziata; U.O. Di Clinica Oncologica

    Chieti, Abruzzo, 66100

  • Ausl Frosinone - Ospedale Umberto I; Divisione Di Oncologia

    Frosinone, Lazio, 03100

  • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica

    Meldola, Emilia-Romagna, 47014

  • Ospedale Misericordia E Dolce; Oncologia Medica

    Prato, Tuscany, 59100

  • Ospedale Di Macerata; Oncologia

    Province of Macerata, The Marches, 62100

  • Ospedale Provinciale Santa Maria delle Croci

    Ravenna, Emilia-Romagna, 48100

Other trials in Italy

Russia9 sites

  • Ivanovo Regional Oncology Dispensary

    Ivanovo, 153040

  • Regional Oncology Hospital Of Kursk; Chemotherapy

    Kislino, Kursk Region, 305524

  • Blokhin Cancer Research Center; Combined Treatment

    Moscow, 115478

  • Russian Oncology Research Center n.a. N.N. Blokhin Dpt of Clinical Pharmacology and Chemotherapy

    Moscow, 115478

  • Omsk Region Clinical Oncology Dispensary; 1St Sergical Department

    Omsk, 644013

  • State Inst. Of Healthcare Orenburg Regional Clinical Oncology Dis

    Orenburg, 460021

  • FSBI"National Medical Research Center of Oncology named after N.N.Petrov" MHRF

    Saint Petersburg, Sankt-Peterburg, 197758

  • SBI of Healthcare Leningrad Regional Oncology Dispensary

    Saint Petersburg, 191104

  • SBI of Healthcare Samara Regional Clinical Oncology Dispensary

    Samara, 443031

Other trials in Russia

Spain9 sites

  • Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología

    A Coruña, 15006

  • Hospital Univ Vall d'Hebron; Servicio de Oncologia

    Barcelona, 08035

  • Hospital Duran i Reynals; Oncologia

    Barcelona, 08907

  • Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia

    Jaén, 23007

  • Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia

    Lleida, 25198

  • Centro Oncologico MD Anderson Internacional; Servicio de Oncologia

    Madrid, 28033

  • Hospital Universitario 12 de Octubre; Servicio de Oncologia

    Madrid, 28041

  • Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia

    Málaga, 29010

  • Hospital Universitario de Canarias;servicio de Oncologia

    San Cristóbal de La Laguna, Tenerife, 38320

Other trials in Spain

France8 sites

  • Centre Oncologie Du Pays Basque

    Bayonne, 64100

  • Clinique Tivoli; Sce Radiotherapie

    Bordeaux, 33000

  • Centre Georges Francois Leclerc; Oncologie 3

    Dijon, 21079

  • Centre Hospitalier Departemental Les Oudairies

    La Roche-sur-Yon, 85925

  • Centre Jean Bernard

    Le Mans, 72015

  • Centre Antoine Lacassagne; Hopital De Jour A2

    Nice, 06189

  • Ico Rene Gauducheau; Oncologie

    Saint-Herblain, 44805

  • Groupe Hospitalier Sud; Oncologie Radiotherapie

    Salouël, 80480

Other trials in France

Argentina7 sites

  • Sanatorio Güemes; Oncología

    Buenos Aires, 1180

  • Centro de Oncologia e Investigacion Buenos Aires (COIBA)

    Buenos Aires, B1884BBF

  • Instituto Medico Especializado (IME); Oncologia

    Caba, 1405

  • Center Instituto Médico Privado I.M.P.; Oncology

    Chaco-resistencia, 3400

  • Policlinica Privada Site la Plata SA; Oncology

    La Plata, B1902CMK

  • Unidad Oncológica De Neuquén

    Neuquén, Q8300HDH

  • Hosp Provincial D. Centenarios; Oncology Dept

    Rosario, S2002KDS

Other trials in Argentina

Thailand6 sites

  • Chulalongkorn Hospital; Medical Oncology

    Bangkok, 10330

  • National Cancer Inst.

    Bangkok, 10400

  • Rajavithi Hospital; Division of Medical Oncology

    Bangkok, 10400

  • Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc

    Bangkok, 10400

  • Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology

    Bangkok, 10700

  • Songklanagarind Hospital; Department of Oncology

    Songkhla, 90110

Other trials in Thailand

China5 sites

  • Jilin Cancer Hospital

    Changchun, 130012

  • Fuzhou General Hospital, PLA Nanjing Military Area Command

    Fuzhou, 110016

  • Zhejiang Cancer Hospital

    Hangzhou, 310022

  • Shanghai First People's Hospital

    Shanghai, 200080

  • Fudan University Shanghai Cancer Center

    Shanghai, 200120

Other trials in China

Poland5 sites

  • Samodzielny Publiczny Kliniczny Nr 1 W Lublinie; Klinika Chirurgii Onkologicznej

    Lublin, 20-081

  • COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej

    Lublin, 20-090

  • Oddzial Chemioterapii Szpitala Klinicznego Nr 1 w Poznaniu

    Poznan, 60-569

  • Zachodniopomorskie Centrum Onkologii, Osrodek Innowacyjnosci, Rozwoju i Badan Klinicznych

    Szczecin, 71-730

  • Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii

    Warsaw, 02-781

Other trials in Poland

South Korea5 sites

  • National Cancer Center; Medical Oncology

    Gyeonggi-do, 410-769

  • Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology

    Seoul, 03080

  • Yonsei Uni College of Medicine, Severance Hospital; Internal Medicine Dept.

    Seoul, 120-752

  • Samsung Medical Centre; Division of Hematology/Oncology

    Seoul, 135-710

  • Asan Medical Center, Uni Ulsan Collegemedicine; Dept.Internal Medicine / Divisionhematology/Oncology

    Seoul, 138-736

Other trials in South Korea

Ecuador4 sites

  • Solca Guayaquil- Sociedad de Lucha Contra El Cáncer; Oncology

    Guayaquil, EC090112

  • Teodoro Maldonado Carbo Hospital; Oncology Service

    Guayaquil, EC090150

  • Hospital Carlos Andrade Marin; Servicio de Oncología

    Quito, 2569

  • Hospital Solca Quito; Oncologia

    Quito, EC170124

Other trials in Ecuador

Guatemala3 sites

  • Centro Oncologico S.A.

    Guatemala City, 01010

  • Grupo Angeles

    Guatemala City, 01015

  • Therapeutic Research Inst. & Lab S.A. (Trial)

    Guatemala City, 01015

Other trials in Guatemala

Latvia3 sites

  • Daugavpils Regional Hospital

    Daugavpils, 5417

  • Rigas Austrumu Kliniska Universitates slimnica, Latvijas Onkologijas centrs

    Riga, LV 1079

  • P.Stradins Clinical University Hospital, Oncology Centre

    Riga, LV-1002

Other trials in Latvia

North Macedonia3 sites

  • Clinical Hospital; Oncology Department

    Bitola, 7000

  • Institute of Radiotherapy Oncology

    Skopje, 1000

  • Private Health Organization Acibadem Sistina Hospital

    Skopje, 1000

Other trials in North Macedonia

Philippines3 sites

  • Cebu Cancer Institute; Perpetual Succour Hospital

    Cebu City, 6000

  • Veterans Memorial Medical Center; Oncology

    Quezon City, 1101

  • St Luke'S Medical Centre; Oncology

    Quezon City, 1114

Other trials in Philippines

Croatia2 sites

  • Clinical Hospital Sisters of Mercy

    Zagreb, 10000

  • University Hospital Centre Zagreb; Clinic For Oncology

    Zagreb, 10000

Other trials in Croatia

Finland2 sites

  • Tampere University Hospital; Dept of Oncology

    Tampere, 33520

  • Turku Uni Central Hospital; Oncology Clinics

    Turku, 20520

Other trials in Finland

Hong Kong2 sites

  • Pamela Youde Nethersole Eastern Hospital; Clinical Oncology

    Hong Kong

  • Prince of Wales Hosp; Dept. Of Clinical Onc

    Shatin

Other trials in Hong Kong

Mexico2 sites

  • Hospital Angeles Metropolitano; Room 220

    Mexico City, Mexico CITY (federal District), 06760

  • Centro Oncologico Estatal ISSEMYM

    Toluca, 50180

Other trials in Mexico

Singapore2 sites

  • National University Hospital; National University Cancer Institute, Singapore (NCIS)

    Singapore, 119228

  • National Cancer Centre; Medical Oncology

    Singapore, 169610

Other trials in Singapore

Canada1 site

  • St. Michael'S Hospital

    Toronto, Ontario, M5B 1W8

Other trials in Canada

Costa Rica1 site

  • Hospital Cima San Jose; Oncology

    San José, 10103

Other trials in Costa Rica

About this study

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

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.

Being tested
Pertuzumab, Placebo, Trastuzumab, Docetaxel
Keywords
Herceptin, Breast cancer, MBC, Taxotere, HER2, HER2 positive breast cancer, HER2 + breast cancer, HER2-positive, HER2-positive metastatic breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PertuzumabDrug

    Also called Perjeta, RO4368451, RG1273

    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.

  • PlaceboDrug

    Placebo (matching pertuzumab) was administered intravenously.

  • TrastuzumabDrug

    Also called Herceptin

    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.

  • DocetaxelDrug

    Also called Taxotere

    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.

Study groups in NCT00567190
Study groupRoleWhat they receive
Pertuzumab + Trastuzumab + DocetaxelExperimentalParticipants randomized to this arm received pertuzumab 420 milligrams (mg) intravenously (IV) once every 3 weeks (q3w) and trastuzumab 6 milligrams per kilogram (mg/kg) IV q3w, plus docetaxel 75 milligrams per square metre of body surface (mg/m^2) IV q3w (for at least 6 cycles; 1 cycle was 21 days). After Cycle 6, continuation of docetaxel treatment was at the discretion of the participant and treating physician. Participants remained in the treatment phase of the study until investigator-assessed radiographic or clinical evidence of disease progression, unmanageable toxicity, or study termination and were followed for survival until death, loss to follow-up, withdrawal of consent, or study termination.
Receives: Drug: Pertuzumab; Drug: Trastuzumab; Drug: Docetaxel
Placebo + Trastuzumab + DocetaxelPlacebo comparatorParticipants randomized to this arm received placebo IV q3w and trastuzumab 6 mg/kg IV q3w, plus docetaxel 75 mg/m^2 IV q3w (for at least 6 cycles; 1 cycle was 21 days). After Cycle 6, continuation of docetaxel treatment was at the discretion of the participant and treating physician. Participants remained in the treatment phase of the study until investigator-assessed radiographic or clinical evidence of disease progression, unmanageable toxicity, or study termination and were followed for survival until death, loss to follow-up, withdrawal of consent, or study termination.
Receives: Drug: Placebo; Drug: Trastuzumab; Drug: Docetaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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 (16)

  1. 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].

    Measured: 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)

  2. 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.

    Measured: 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)

  3. 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.

    Measured: 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)

  4. 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.

    Measured: 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)

  5. 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.

    Measured: Every 9 weeks from Baseline until investigator-determined progressive disease, up to the primary completion date (up to 3 years, 3 months)

  6. 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.

    Measured: 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)

  7. 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.

    Measured: 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)

  8. 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.

    Measured: 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)

  9. 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.

    Measured: 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)

  10. 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.

    Measured: 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)

  11. 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

    Measured: 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)

  12. 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.

    Measured: From Day 43 after discontinuation of all study medication to end of post-treatment follow-up period (up to 3 years)

  13. 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.

    Measured: Every 9 weeks from the date of randomization until Treatment Discontinuation Visit (see Description for time on study treatment per arm)

  14. 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.

    Measured: 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)

  15. 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

    Measured: 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)

  16. 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

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Dec 2007 (estimated)
  2. Study start12 Feb 2008
  3. Primary completion13 May 2011
  4. Study completion23 Nov 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
808 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00567190
Sponsor's protocol ID
TOC4129g
Other IDs
WO20698, 2007-002997-72
Acronym
CLEOPATRA
Status last verified
Dec 2019
First submitted
3 Dec 2007
Last updated
13 Dec 2019
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 22149875

  • 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.

    PubMed 32171426

  • 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.

    PubMed 29112701

  • 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.

    PubMed 28057664

  • 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.

    PubMed 27964843

  • 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.

    PubMed 25693012

  • 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.

    PubMed 25332247

  • 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.

    PubMed 24685829

  • 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.

    PubMed 24129974

  • 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.

    PubMed 23868905

  • 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.

    PubMed 23602601

  • 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.

    PubMed 21147694

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pertuzumab, Trastuzumab and Docetaxel in people with Metastatic Breast Cancer, run by Genentech, Inc. at 322 sites in 26 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 322 sites in United States, Japan, Brazil, Germany, United Kingdom and 21 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Sep 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival (PFS) Determined by an Independent Review Facility (time frame: 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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00567190, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2019.

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