A Study of Trastuzumab Emtansine (T-DM1) Plus Pertuzumab/Pertuzumab Placebo Versus Trastuzumab [Herceptin] Plus a Taxane in Participants With Metastatic Breast Cancer (MARIANNE)

A Randomized, 3 Arm, Multicenter, Phase III Study to Evaluate the Efficacy and the Safety of T-DM1 Combined With Pertuzumab or T-DM1 Combined With Pertuzumab-Placebo (Blinded for Pertuzumab), Versus the Combination of Trastuzumab Plus Taxane, as First Line Treatment in HER2 Positive Progressive or Recurrent Locally Advanced or Metastatic Breast Cancer

This randomized, 3-arm, multicenter, phase III study will evaluate the efficacy and safety of trastuzumab emtansine (T-DM1) with pertuzumab or trastuzumab emtansine (T-DM1) with pertuzumab-placebo (blinded for pertuzumab), versus the combination of trastuzumab (Herceptin) plus taxane (docetaxel or paclitaxel) in participants with HER2-positive progressive or recurrent locally advanced or previously untreated metastatic breast cancer. Participants will be randomized to 1 of 3 treatment arms (Arms A, B or C). Arm A will be open-label, whereas Arms B and C will be blinded.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: docetaxel; Drug: paclitaxel; Drug: trastuzumab [Herceptin]; Drug: pertuzumab; Drug: trastuzumab emtansine; Drug: pertuzumab-placebo

• Study Type: Interventional
• Enrollment (Actual): 1095
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1025
    • Fundación Investigar
  • San Miguel de Tucuman, Argentina, T4000IAK
    • Centro Médico San Roque
• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2060
      • Mater Misericordiae Hospital; Chemotherapy Cottage
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle; Medical Oncology
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Wesley Medical Centre; Clinic For Haematology and Oncology
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital; Oncology
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter Maccallum Cancer Institute; Medical Oncology
• Austria
  • Salzburg, Austria, 5020
    • Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.
  • Wien, Austria, 1090
    • Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Abt. für Onkologie
• Bahamas
  • Nassau, Bahamas, 09311
    • Oncology Consultants Limited
• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires St-Luc
  • Namur, Belgium, 5000
    • Clinique Ste-Elisabeth
  • Wilrijk, Belgium, 2610
    • Sint Augustinus Wilrijk
• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina, 78000
    • University Clinical Centre of the Republic of Srpska
  • Sarajevo, Bosnia and Herzegovina, 71000
    • Clinic of Oncology, University Clinical Center Sarajevo
• Brazil
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20560-120
      • *X*Instituto Nacional do Cancer - INCA
  • RN
    • Natal, RN, Brazil, 59040150
      • Liga Norte Riograndense Contra o Câncer
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Hospital Sao Lucas - PUCRS
    • Porto Alegre, RS, Brazil, 90430-090
      • Clinica de Oncologia de Porto Alegre - CliniOnco
    • Porto Alegre, RS, Brazil, 90040-373
      • Hospital Nossa Senhora da Conceicao
  • SC
    • Itajai, SC, Brazil, 88301-220
      • Clinica de Neoplasias Litoral
  • SP
    • Sao Paulo, SP, Brazil, 01246-000
      • Instituto do Cancer do Estado de Sao Paulo - ICESP
    • Sao Paulo, SP, Brazil, 01317-000
      • Hospital Perola Byington
• Canada
  • Quebec, Canada, G1S 4L8
    • CHU de Québec ? Hôpital du Saint-Sacrement / ONCOLOGY
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute; Clinical Trials
  • Ontario
    • Toronto, Ontario, Canada, M2J 1V1
      • North York General Hospital
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Cuse - Centre Universitaire De Sante; Site Fleurimont
• Colombia
  • Bogota, Colombia, 11001
    • Clinica del Country
  • Bucaramanga, Colombia
    • Instituto Colombiano Para El Avance De La Medicina: Icamedic
  • Cali, Colombia
    • Centro Médico Imbanaco
  • Pasto, Colombia
    • Instituto Cancerologico de Nariño
• Czechia
  • Brno, Czechia, 656 53
    • Masarykuv Onkologicky Ustav
  • Olomouc, Czechia, 779 00
    • Fakultni nemocnice Olomouc; Onkologicka klinika
  • Praha, Czechia, 180 00
    • Fakultni Nemocnice Na Bulovce; Ustav Radiacni Onkologie
  • Praha 2, Czechia, 128 08
    • Fakultni Poliklinika Vseobecne Fakultni Niemocnice; Onkologicka Klinika
• Denmark
  • Vejle, Denmark, 7100
    • Vejle Sygehus; Onkologisk Afdeling
• France
  • Besancon, France, 25030
    • HOPITAL JEAN MINJOZ; Oncologie
  • Clermont Ferrand, France, 63011
    • Centre Jean Perrin; Hopital De Jour
  • Lille, France, 59020
    • Centre Oscar Lambret; Senologie
  • Marseille, France, 13273
    • Institut Paoli Calmettes; Oncologie Medicale
  • Montpellier, France, 34298
    • Institut Régional du Cancer Montpellier
  • Nancy, France, 54100
    • Centre D'Oncologie de Gentilly; Oncology
  • Paris, France, 75231
    • Institut Curie; Oncologie Medicale
  • Paris, France, 75970
    • HOPITAL TENON; Cancerologie Medicale
  • Paris, France, 75475
    • Hopital Saint Louis; Service Onco Thoracique
  • Poitiers, France, 86021
    • Chu La Miletrie; Radiotherapie
  • Saint Cloud, France, 92210
    • Centre Rene Huguenin; ONCOLOGIE GENETIQUE
  • St Priest En Jarez, France, 42271
    • Institut de Cancerologie de La Loire; Radiotherapie
• Germany
  • Essen, Germany, 45136
    • Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum
  • Halle, Germany, 06120
    • Universitätsklinikum Halle (Saale); Universitätsklinik Und Poliklinik Für Gynäkologie
  • Hamburg, Germany, 20249
    • Facharztzentrum Eppendorf, Studien GbR
  • Hannover, Germany, 30177
    • MVZ Onko Medical GmbH Hannover, Ralf Lohse (Geschäftsführer)
  • Heidelberg, Germany, 69120
    • Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg
  • Magdeburg, Germany, 39108
    • Universitätsklinikum Magdeburg; Frauenheilkunde & Geburtshilfe
  • Mainz, Germany, 55131
    • Universitätsmedizin Mainz; Klinik u. Poliklinik f. Geburtshilfe u. Frauenheilkunde
  • Minden, Germany, 32429
    • Mühlenkreiskliniken; Johannes Wesling Klinikum Minden; Klinik für Frauenheilkunde und Geburtshilfe
  • Muenchen, Germany, 80637
    • Rotkreuzklinikum München; Frauenklinik
  • Trier, Germany, 54290
    • Klinikum Mutterhaus der Borromaeerinnen gGmbH; Haematologie/Onkologie
• Greece
  • Athens, Greece, 115 28
    • Alexandras General Hospital of Athens; Oncology Department
  • Heraklion, Greece, 711 10
    • Univ General Hosp Heraklion; Medical Oncology
  • Larissa, Greece
    • University Hospital of Larissa; Oncology
• Guatemala
  • Guatemala, Guatemala, 01010
    • Centro Oncológico Sixtino / Centro Oncológico SA
  • Guatemala City, Guatemala, 01015
    • Grupo Angeles
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem Onkologiai Központ
  • Budapest, Hungary, 1032
    • Szent Margit Hospital; Dept. of Oncology
  • Budapest, Hungary, 1125
    • Semmelweis Egyetem Aok; Iii.Sz. Belgyogyaszati Klinika
  • Pécs, Hungary, 7623
    • Pécsi Tudományegyetem; Klinikai Központ Onkoterápiás Intézet
• Italy
  • Calabria
    • Catanzaro, Calabria, Italy, 88100
      • Campus Universitario S.Venuta; Centro Oncologico T.Campanella
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
    • Modena, Emilia-Romagna, Italy, 41124
      • A.O. Universitaria Policlinico Di Modena; Ematologia
    • Reggio Emilia, Emilia-Romagna, Italy, 42100
      • Arcispedale Santa Maria Nuova; Oncologia
    • Rimini, Emilia-Romagna, Italy, 47900
      • Ospedale Degli Infermi; Divisione Di Oncologia
  • Friuli-Venezia Giulia
    • Udine, Friuli-Venezia Giulia, Italy, 33100
      • Azienda Ospedaliero-Universitaria Dipartimento Interaziendale Di Oncologia
  • Lombardia
    • Milano, Lombardia, Italy, 20141
      • Istituto Europeo di Oncologia
    • Pavia, Lombardia, Italy, 27100
      • Fondazione Salvatore Maugeri
    • Rozzano (MI), Lombardia, Italy, 20089
      • IRCCS Istituto Clinico Humanitas; Oncologia
  • Sicilia
    • Catania, Sicilia, Italy, 95126
      • Centro Catanese Di Oncologia; Oncologia Medica
    • Messina, Sicilia, Italy, 98158
      • Ospedale Papardo- Piemonte;Oncologia Medica
  • Toscana
    • Prato, Toscana, Italy, 59100
      • Ospedale Misericordia E Dolce; Oncologia Medica
  • Umbria
    • Perugia, Umbria, Italy, 06156
      • Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica
• Japan
  • Aichi, Japan, 464-8681
    • Aichi Cancer Center Hospital, Breast Oncology
  • Ehime, Japan, 791-0280
    • Natl Hosp Org Shikoku; Cancer Ctr, Surgery
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center;Breast Oncology
  • Gifu, Japan, 501-1194
    • Gifu University Hospital; Digestive Surgery
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital; Breast Surgery
  • Hokkaido, Japan, 003-0804
    • National Hospital Organization Hokkaido Cancer Center; Breast Surgery
  • Hyogo, Japan, 663-8501
    • Hyogo College Of Medicine; Breast And Endocrine Surgery
  • Hyogo, Japan, 673-8558
    • Hyogo Cancer Center; Breast Surgery
  • Ishikawa, Japan, 920-8641
    • Kanazawa University Hospital; Breast Oncology
  • Iwate, Japan, 028-3695
    • Iwate Med Univ School of Med; Surgery
  • Kagoshima, Japan, 892-0833
    • Sagara Hospital; Breast Surgery
  • Kanagawa, Japan, 259-1193
    • Tokai University Hospital, Breast Surgery
  • Kumamoto, Japan, 862-8505
    • Kumamoto City Hospital, Breast and Endocrine Surgery
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Hospital; Breast and Endocrine Surgery
  • Kyoto, Japan, 606-8507
    • Kyoto University Hospital; Breast Surgery
  • Miyagi, Japan, 980-8574
    • Tohoku University Hospital; General Surgery
  • Niigata, Japan, 951-8566
    • Niigata Cancer Ctr Hospital; Breast Surgery
  • Okayama, Japan, 701-0114
    • Kawasaki Medical School Hospital; Breast and Thyroid Surgery
  • Osaka, Japan, 540-0006
    • National Hospital Organization Osaka National Hospital; Breast Surgery
  • Osaka, Japan, 565-0871
    • Osaka University Hospital; Breast and Endocrine Surgery
  • Saitama, Japan, 362-0806
    • Saitama Cancer Center, Breast Oncology
  • Saitama, Japan, 350-1298
    • Saitama Medical University International Medical Center; Medical Oncology
  • Shizuoka, Japan, 411-8777
    • Shizuoka Cancer Center; Breast Surgery
  • Shizuoka, Japan, 420-8527
    • Shizuoka General Hospital; Breast Surgery
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital; Medical Oncology
  • Tokyo, Japan, 135-8550
    • The Cancer Inst. Hosp. of JFCR; Breast Oncology Center
  • Tokyo, Japan, 160-0023
    • Tokyo Medical Uni. Hospital; Breast Oncology
  • Tokyo, Japan, 105-8470
    • Toranomon Hospital; Breast and Endocrine Surgery
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of, 463-707
    • Seoul National University Bundang Hospital; Hematology Medical Oncology
  • Seoul, Korea, Republic of, 03080
    • Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Centre; Division of Hematology/Oncology
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center, Uni Ulsan Collegemedicine; Dept.Internal Medicine / Divisionhematology/Oncology
  • Seoul, Korea, Republic of, 152-703
    • Korea University Guro Hospital; Oncology
• Malaysia
  • Selangor, Malaysia, 46150
    • Sunway Medical Centre
  • FED. Territory OF Kuala Lumpur
    • Kuala Lumpur, FED. Territory OF Kuala Lumpur, Malaysia, 59100
      • Pantai Hospital Kuala Lumpur; Dept of Oncology & Radiotherapy
  • Selangor
    • Petaling Jaya, Selangor, Selangor, Malaysia, 46050
      • Beacon International Specialist Centre
• Mexico
  • Aguascalientes, Mexico, 20230
    • Centenario Hospital Miguel Hidalgo
  • Toluca, Mexico, 50180
    • Centro Oncológico Estatal; ISSSEMYM Oncología
  • Guerrero
    • Acapulco, Guerrero, Mexico, 39670
      • Centro de Investigacion; Clinica Del Pacifico
  • Nuevo LEON
    • Monterrey, Nuevo LEON, Mexico, 64020
      • Centro Universitario Contra El Cancer
  • Oaxaca
    • Oaxaca de Juárez, Oaxaca, Mexico, 68000
      • Oaxaca Site Management Organization
  • Sonora
    • Obregon, Sonora, Mexico, 85000
      • Hospital Privado San Jose; Oncologia
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland city hospital; Auckland Regional Cancer Centre and Blood Service
  • Hamilton, New Zealand
    • Waikato Hospital; Regional Cancer Center
• North Macedonia
  • Skopje, North Macedonia, 1000
    • Private Health Organization Acibadem Sistina Hospital
• Panama
  • Panama, Panama, 0832-02723
    • The Panama Clinic
• Peru
  • Arequipa, Peru, 04001
    • Hospital Nacional Carlos Alberto Seguin Escobedo-Essalud; Oncology & Haemathology
  • Lima, Peru, 11
    • Hospital Nacional Edgardo Rebagliati Martins; Oncologia
  • Piura, Peru, 20011
    • Unidad de Investigacion Oncologia Clinica ? Piura; Unidad de Oncología Clínica
• Philippines
  • Cebu City, Philippines, 6000
    • Cebu Cancer Institute; Perpetual Succour Hospital
  • San Juan, Philippines, 1502
    • Cardinal Santos Medical Center
• Poland
  • Bydgoszcz, Poland, 85-796
    • Centrum Onkologii;Im. Franciszka Lukaszczyka;Onkologii
  • Gdansk, Poland, 80-952
    • Medical University of Gdansk
  • Krakow, Poland, 31-115
    • Centrum Onkologii, Instytut, Klinika Chemioterapii; Oddzial Chemoterapii
  • Lublin, Poland, 20-090
    • COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej
  • Warszawa, Poland, 02-781
    • Cent.Onkologii-Instytut im. M. S-Curie, Klinika Now. Piersi i Chirurgii Rekon
• Portugal
  • Porto, Portugal, 4200-072
    • IPO do Porto; Servico de Oncologia Medica
• Romania
  • Bucharest, Romania
    • Coltea Hospital; Oncology
  • Cluj Napoca, Romania, 400015
    • Prof. Dr. I. Chiricuta Institute of Oncology
  • Cluj-Napoca, Romania, 400006
    • Cluj Clinical County Hospital; Oncology Dept
• Russian Federation
  • Ivanovo, Russian Federation, 153040
    • Ivanovo regional oncology dispensary
  • Samara, Russian Federation, 443031
    • SBI of Healthcare Samara Regional Clinical Oncology Dispensary
  • Stavropol, Russian Federation, 355045
    • SBI of Healthcare of Stavropol region Stavropol Regional Clinical Oncology Dispensary
  • Tula, Russian Federation, 300053
    • Tula Regional Oncology Dispensary
  • Vladimir, Russian Federation, 600009
    • GUZ Vladimir Regional Clinical Oncological Dispensary
  • Moskovskaja Oblast
    • Moscow, Moskovskaja Oblast, Russian Federation, 143423
      • Moscow city oncology hospital; #62 of Moscow Healthcare Department
    • Moskva, Moskovskaja Oblast, Russian Federation, 115478
      • Blokhin Cancer Research Center; Combined Treatment
  • Rjazan
    • Ryazan, Rjazan, Russian Federation, 390026
      • Ryazan State Medical University named after I.P.Pavlov
  • Stavropol
    • Pyatigorsk, Stavropol, Russian Federation, 357502
      • State Budget Institution of Healthcare of Stavropol region Pyatigorsk Oncology Dispensary
  • Tatarstan
    • Kazan, Tatarstan, Russian Federation, 420029
      • Clinical Oncology Dispensary of Ministry of Health of Tatarstan
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar; Servicio de Oncologia
  • Jaen, Spain, 23007
    • Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia
  • La Coruña, Spain, 15006
    • Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre; Servicio de Oncologia
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz; Servicio de Oncologia
  • Malaga, Spain, 29010
    • Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Hospital General Universitario de Elche; Servicio de Oncologia
  • Barcelona
    • Sant Andreu de La Barca, Barcelona, Spain, 08740
      • Hospital Univ Vall d'Hebron; Servicio de Oncologia
  • LA Coruña
    • Santiago de Compostela, LA Coruña, Spain, 15706
      • Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
• Sweden
  • Malmö, Sweden, 200 25
    • Skånes Universitetssjukhus; Kliniska Forskningsenheten Onkologimottagning medicinsk behandling
• Switzerland
  • Baden, Switzerland, 5404
    • Kantonsspital Baden; Medizinische Klinik, Onkologie
  • Basel, Switzerland, 4031
    • Universitaetsspital Basel; Onkologie
  • Chur, Switzerland, 7000
    • Kantonsspital Graubünden Medizin Onkologie; Onkologie und Hämatologie
• Taiwan
  • Changhua, Taiwan, 500
    • Changhua Christian Hospital; Hematology-Oncology
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical Uni Chung-Ho Hospital; Dept of Surgery
  • Taipei, Taiwan, 100
    • National Taiwan Uni Hospital; Dept of Oncology
  • Taipei, Taiwan, 114
    • Tri-Service General Hospital; Hematology and Oncology
• Thailand
  • Bangkok, Thailand, 10700
    • Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology
  • Bangkok, Thailand, 10400
    • National Cancer Inst.
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc
  • Bangkok, Thailand, 10400
    • Rajavithi Hospital; Division of Medical Oncology
  • Chiang Mai, Thailand, 50200
    • Maharaj Nakorn Hospital; Internal Medicine
  • Songkhla, Thailand, 90110
    • Songklanagarind Hospital; Department of Oncology
• Turkey
  • Adana, Turkey, 01230
    • Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology
  • Adana, Turkey, 01330
    • Cukurova Uni Faculty of Medicine; Medical Oncology
  • Ankara, Turkey, 06500
    • Gazi Uni Medical Faculty Hospital; Oncology Dept
  • Izmir, Turkey, 35100
    • Ege Uni Medical Faculty Hospital; Oncology Dept
• United Kingdom
  • Bristol, United Kingdom, BS2 8ED
    • Bristol Haematology and Oncology centre
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust
  • Cornwall, United Kingdom, TR1 3LQ
    • Royal Cornwall Hospital; Dept of Clinical Oncology
  • Glasgow, United Kingdom, G12 0YN
    • The Beatson West of Scotland Cancer Centre; Cancer Clinical Trials Unit
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary; Dept. of Medical Oncology
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital; Dept of Oncology
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden Hospital; Dept of Med-Onc
  • London, United Kingdom, SE1 9RT
    • Guys Hospital; Management Offices
  • Manchester, United Kingdom, M20 4QL
    • Christie Hospital; Breast Cancer Research Office
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham City Hospital; Oncology
  • Peterborough, United Kingdom, PE 3 9GZ
    • Peterborough City Hospital; Oncology Ward
  • Portsmouth, United Kingdom, PO6 3LY
    • Queen Alexandra Hospital, Portsmouth
  • Sheffield, United Kingdom, S10 2SJ
    • Weston Park Hospital; Cancer Clinical Trials Centre
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital; Somers Cancer Research Building
  • Stoke-on-Trent, United Kingdom, ST4 6QG
    • Uni Hospital of North Staffordshire; Staffordshire Oncology Centre
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital; Dept of Medical Oncology
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72204
      • Uni of Arkansas For Medical Sciences; Arkansas Cancer Research Center
  • California
    • La Jolla, California, United States, 92037
      • Scripps Cancer Center
    • La Jolla, California, United States, 92093
      • University of California; Moores Cancer Center
    • Montebello, California, United States, 90640
      • Clnc L Trials & Rsch Assoc-Inc
    • San Diego, California, United States, 92108
      • Southern California Kaiser Permanente
    • Santa Ana, California, United States, 92705
      • Breastlink Medical Group Inc
    • Vallejo, California, United States, 94589
      • Kaiser Permanente; Oncology Clinical Trials
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Smilow Cancer Hospital at Yale New Haven
  • Florida
    • Aventura, Florida, United States, 33180
      • Innovative Medical Research of South Florida
    • Coral Springs, Florida, United States, 33065-5701
      • Northwest Oncology/ Hematology Assoc.
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists; SCRI
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic-Jacksonville
    • Miami, Florida, United States, 33136
      • Uni of Miami School of Medicine; Sylvester Comprehensive Cancer Center
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer & Blood Center, LLC; Research
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Cancer Research Center of Hawaii; Clinical Sciences
  • Idaho
    • Boise, Idaho, United States, 83712
      • Mountain States Tumor Inst.
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Uni of Chicago
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Harvey, Illinois, United States, 60426
      • Ingalls Memorial Hospital
    • Maywood, Illinois, United States, 60153
      • Loyola University Med Center
    • Peoria, Illinois, United States, 61615
      • Illinois Cancer Care
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Melvin and Bren Simon Cancer Center
    • Lafayette, Indiana, United States, 47905
      • Horizon Oncology Research, Inc.
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • James Graham Brown Cancer Center, University of Louisville
  • Maine
    • Scarborough, Maine, United States, 04074
      • New England Cancer Specialists
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Anne Arundel Health System Research Instit-Annapolis Oncology Ctr
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health Grand Rapids
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • University of Minnesota.
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic Rochester
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • St. John'S Mercy Medical Center; David C. Pratt Cancer Center
    • Springfield, Missouri, United States, 65804
      • Mercy Clinic Cancer & Hematology
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Med Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack Uni Medical Center; Northern Nj Cancer Center
    • New Brunswick, New Jersey, United States, 08901
      • Cancer Inst. of New Jersey
  • New Mexico
    • Farmington, New Mexico, United States, 87401
      • San Juan Oncology Associates
  • New York
    • Fresh Meadows, New York, United States, 11366
      • Queens Medical Associates
    • Jamaica, New York, United States, 11432
      • Queens Hospital Center
    • Lake Success, New York, United States, 11042
      • Arena Oncology Associates
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10065
      • Weill Medical College of Cornell Uni
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Hem-Oncology Assoc
    • Hickory, North Carolina, United States, 28602
      • Carolina Oncology Specialists, PA - Hickory
    • Washington, North Carolina, United States, 27889
      • Marion L. Shepard Cancer Center
  • North Dakota
    • Fargo, North Dakota, United States, 58102
      • Sanford Roger Maris Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care - SCRI
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Charleston Oncology, P .A
    • Charleston, South Carolina, United States, 29425
      • Medical University of SC (MUSC)
    • Columbia, South Carolina, United States, 29210
      • South Carolina Oncology Associates - SCRI
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Scri Tennessee Oncology Chattanooga
    • Germantown, Tennessee, United States, 38138
      • West Clinic
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Ctr
    • Nashville, Tennessee, United States, 37203
      • Tennessee Onc., PLLC - SCRI
  • Texas
    • Amarillo, Texas, United States, 79106
      • The Don & Sybil Harrington Cancer Center; Department of Clinical Research
    • Dallas, Texas, United States, 75390-9063
      • Uni of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Uni of Texas - Md Anderson Cancer Center; Dept of Breast Medical Oncology
  • Utah
    • Ogden, Utah, United States, 84403
      • Northern Utah Associates
  • Washington
    • Everett, Washington, United States, 98201
      • The Providence Regional Medical Center Everett
    • Seattle, Washington, United States, 98195
      • University of Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult participants >/=18 years of age
• HER2-positive breast cancer
• Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease, and be a candidate for chemotherapy. Participants with locally advanced disease must have recurrent or progressive disease, which must not be amenable to resection with curative intent.
• Participants must have measurable and/or non-measurable disease which must be evaluable per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
• Adequate organ function as determined by laboratory results

Exclusion Criteria:

• History of prior (or any) chemotherapy for metastatic breast cancer or recurrent locally advanced disease
• An interval of <6 months from the last dose of vinca-alkaloid or taxane cytotoxic chemotherapy until the time of metastatic diagnosis
• Hormone therapy <7 days prior to randomization
• Trastuzumab therapy and/or lapatinib (neo- or adjuvant setting) <21 days prior to randomization
• Prior trastuzumab emtansine or pertuzumab therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trastuzumab + Taxane (docetaxel or paclitaxel)	Drug: docetaxel; 75 mg/m2 or 100 mg/m2 intravenously every 3 weeks for a minimum of 6 cycles.; Drug: paclitaxel; 80 mg/m2 intravenously weekly for a minimum of 18 weeks; Drug: trastuzumab [Herceptin]; trastuzumab [Herceptin] doses when administered with docetaxel: 8 mg/kg intravenously on cycle 1 followed by 6 mg/kg every 3 weeks in subsequent cycles or trastuzumab (Herceptin) doses when administered with paclitaxel: 4 mg/kg intravenously on day 1 of cycle 1 followed by 2 mg/kg weekly starting on day 8 of cycle 1.
Experimental: Trastuzumab emtansine + pertuzumab	Drug: pertuzumab; 840 mg intravenously on day 1 of cycle 1 followed by 420 mg intravenously every 3 weeks in subsequent cycles; Drug: trastuzumab emtansine; 3.6 mg/kg intravenously every 3 weeks
Experimental: Trastuzumab emtansine + pertuzumab placebo	Drug: trastuzumab emtansine; 3.6 mg/kg intravenously every 3 weeks; Drug: pertuzumab-placebo; 840 mg intravenously on day 1 of cycle 1 followed by 420 mg intravenously every 3 weeks in subsequent cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Death or Disease Progression According to Independent Review Facility (IRF) Assessment	Tumor assessments were performed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. Disease progression was defined as a greater than or equal to (≥) 20 percent (%) and 5-millimeter (mm) increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). The percentage of participants with death or disease progression was calculated as [number of participants with event divided by the number analyzed] multiplied by 100.	Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
Progression-Free Survival (PFS) According to IRF Assessment	Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. PFS was defined as the time from randomization to first documented disease progression or death from any cause. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). Median duration of PFS was estimated using Kaplan-Meier analysis, and corresponding confidence intervals (CIs) were computed using the Brookmeyer-Crowley method.	Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Died Prior to Clinical Cutoff	The percentage of participants who died prior to clinical cutoff was calculated as [number of participants with event divided by the number analyzed] multiplied by 100.	Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination)
Overall Survival (OS) at Clinical Cutoff	OS was defined as the time from randomization to death from any cause. Median duration of OS was estimated using Kaplan-Meier analysis, and corresponding CIs were computed using the Brookmeyer-Crowley method.	Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination)
Percentage of Participants With Death or Disease Progression According to Investigator Assessment	Tumor assessments were performed by the investigator according to RECIST version 1.1. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). The percentage of participants with death or disease progression was calculated as [number of participants with event divided by the number analyzed] multiplied by 100.	Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
PFS According to Investigator Assessment	Tumor assessments were performed by the investigator according to RECIST version 1.1. PFS was defined as the time from randomization to first documented disease progression or death from any cause. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). Median duration of PFS was estimated using Kaplan-Meier analysis, and corresponding CIs were computed using the Brookmeyer-Crowley method.	Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
Percentage of Participants Experiencing Treatment Failure	Treatment failure was defined as the discontinuation of all study medications in the treatment arm for any reason including disease progression, treatment toxicity, death, physician decision, or participant withdrawal. The percentage of participants with treatment failure was calculated as [number of participants with event divided by the number analyzed] multiplied by 100.	Up to 48 months from randomization until clinical cutoff of 16-Sept-2014
Time to Treatment Failure (TTF)	Treatment failure was defined as the discontinuation of all study medications in the treatment arm for any reason including disease progression, treatment toxicity, death, physician decision, or participant withdrawal. TTF was defined as the time from randomization to treatment failure. Median TTF was estimated using Kaplan-Meier analysis, and corresponding CIs were computed using the Brookmeyer-Crowley method.	Up to 48 months from randomization until clinical cutoff of 16-Sept-2014
One-Year Survival Rate	The percentage of participants alive at 1 year after randomization was estimated as the one-year survival rate using Kaplan-Meier analysis, and corresponding CIs were computed using Greenwood's estimate of the standard error.	From randomization until 1 year
Percentage of Participants With Grade ≥3 Adverse Events	Adverse events were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activity of daily living with inability to perform bathing, dressing and undressing, feeding self, using the toilet, taking medications but not bedridden. Grade 4: An immediate threat to life. Urgent medical intervention is required in order to maintain survival. Grade 5: Death.	Up to 50 months from randomization until clinical cutoff of 16-Sept-2014 (continuously until 28 days after last dose
Percentage of Participants Who Died at 2 Years		From randomization until 2 years
Overall Survival Truncated at 2 Years	Overall Survival truncated at 2 years was defined as the percentage of participants alive at 2 years.	From randomization until 2 years
Percentage of Participants With Grade 5 Adverse Events	Adverse events were graded according to NCI CTCAE version 4.0. Grade 5 adverse events are those events which led to death.	Up to 50 months from randomization until clinical cutoff of 16-Sept-2014 (continuously until 28 days after last dose)
Percentage of Participants With Grade 3-4 Laboratory Parameters	Laboratory results were graded according to NCI CTCAE version 4.0. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activity of daily living with inability to perform bathing, dressing and undressing, feeding self, using the toilet, taking medications but not bedridden. Grade 4: An immediate threat to life. Urgent medical intervention is required in order to maintain survival.	Day 1, 8, and 15 of Cycle 1-3 and on Day 1 of each subsequent cycle up to 50 months from randomization until clinical cutoff of 16-Sept-2014
Percentage of Participants With Decline of ≥2 Points From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status	The ECOG performance status is a scale used to quantify cancer participants' general well-being and activities of daily life. The scale ranges from 0 to 5, with 0 denoting perfect health and 5 indicating death. The 6 categories are 0=Asymptomatic (Fully active, able to carry on all predisease activities without restriction), 1=Symptomatic but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature), 2=Symptomatic, < 50% in bed during the day (Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours), 3=Symptomatic, > 50% in bed, but not bedbound (Capable of only limited self-care, confined to bed or chair 50% or more of waking hours), 4=Bedbound (Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair), 5=Death.	Baseline, Day 1 of every Cycle up to Clinical Data Cut (up to 48 months)
Hospitalization Days	Hospitalization was defined as a non-administration-related hospitalization due to serious adverse event, while on study treatment. Reported values represent number of days admitted per participants.	Up to 48 months from randomization until clinical cutoff of 16-Sept-2014
Percentage of Participants With Hospitalization	Hospitalization was defined as a non-administration-related hospitalization due to serious adverse event, while on study treatment.	Up to 48 months from randomization until clinical cutoff of 16-Sept-2014
Percentage of Participants With Objective Response According to IRF Assessment	Objective response was defined as having complete response (CR) or partial response (PR), assessed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. CR was defined as the disappearance of all target and non-target lesions and short-axis reduction in pathological lymph nodes to <10 mm. PR was defined as a ≥30% decrease in sum of diameters of target lesions, taking as reference the Baseline sum. Response was determined using 2 consecutive tumor assessments at least 4 weeks apart. The percentage of participants with a best overall response of CR or PR (ie, the objective response rate [ORR]) was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100. Corresponding CIs were computed using the Blyth-Still-Casella exact method.	Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
Percentage of Participants With Objective Response According to Investigator Assessment	Objective response was defined as having CR or PR, assessed according to RECIST version 1.1, by investigator. CR was defined as the disappearance of all target and non-target lesions and short-axis reduction in pathological lymph nodes to <10 mm. PR was defined as a ≥30% decrease in sum of diameters of target lesions, taking as reference the Baseline sum. Response was determined using 2 consecutive tumor assessments at least 4 weeks apart. The percentage of participants with a best overall response of CR or PR (ie, the ORR) was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100. Corresponding CIs were computed using the Blyth-Still-Casella exact method.	Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
Duration of Response According to IRF Assessment	Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. Duration of response was defined as the time from confirmed PR or CR to first documented disease progression or death from any cause. CR was defined as the disappearance of all target lesions and non-target lesions and short-axis reduction in pathological lymph nodes to <10 mm. PR was defined as a ≥30% decrease in sum of diameters of target lesions, taking as reference the Baseline sum. Response was determined using 2 consecutive tumor assessments at least 4 weeks apart. Median duration of response was estimated using Kaplan-Meier analysis, and corresponding CIs were computed using the Brookmeyer-Crowley method.	Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD) According to IRF Assessment	Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. CR was defined as the disappearance of all target and non-target lesions and short-axis reduction in pathological lymph nodes to <10 mm. PR was defined as a ≥30% decrease in sum of diameters of target lesions, taking as reference the Baseline sum. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient (20%) increase to qualify for disease progression. Response was determined using 2 consecutive tumor assessments at least 4 weeks apart. The percentage of participants with a best overall response of CR, PR, or SD was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100.	Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
Percentage of Participants Experiencing a Clinically Significant Increase in Taxane-Related Treatment Symptoms as Measured by Taxane Subscale of the Functional Assessment of Cancer Therapy (FACT) Taxane (FACT-TaxS) Score	The FACT-Taxane is a self-reported instrument which measures the health-related quality of life (HRQOL) of participants receiving taxane-containing chemotherapy. The FACT-TaxS consists of 16 items including 11 neurotoxicity-related questions and 5 additional questions assessing arthralgia, myalgia, and skin discoloration. Items are rated from 0 (not at all) to 4 (very much) and a total score is inversely derived. Scores may range from 0 to 64, with higher scores indicating fewer/no symptoms. A minimally clinically important difference in treatment-related symptoms was defined as a ≥5% decrease (ie, 3.2 points) in FACT-TaxS score from Baseline. The percentage of participants with treatment-related symptoms was calculated using following formula: [number of participants meeting the above threshold divided by the number analyzed] multiplied by 100. Corresponding CIs were computed using the Blyth-Still-Casella exact method.	Up to 39 months from randomization until clinical cutoff of 16-Sept-2014 (at Baseline, on Day 1 of Cycles 2 to 8 and every even-numbered cycle thereafter and/or up to 42 days after last dose)
Percentage of Participants Reporting Nausea According to the Relevant Single Items of The FACT Colorectal Cancel (FACT-C) Module	The FACT-C is a self-reported instrument which measures HRQOL pertaining to colorectal cancer. Response options on each question may range from 0 (not at all) to 4 (very much). The percentage of participants with nausea was calculated using following formula: [number of participants with any level of either symptom divided by the number analyzed] multiplied by 100.	At Baseline, Day 8 of Cycle 1, and Days 1 and 8 of Cycle 2
Percentage of Participants Reporting Diarrhea According to the Relevant Single Items of The FACT-C Module	The FACT-C is a self-reported instrument which measures HRQOL pertaining to colorectal cancer. Response options on each question may range from 0 (not at all) to 4 (very much). The percentage of participants with diarrhea was calculated using following formula: [number of participants with any level of either symptom divided by the number analyzed] multiplied by 100.	At Baseline, Day 8 of Cycle 1, and Days 1 and 8 of Cycle 2
Percentage of Participants With a Clinically Significant Deterioration in Health Related Quality of Life (HRQoL) as Measured by FACT Breast (FACT-B) Trial Outcome Index-Physical Function Breast (TOI-PFB) Score	The FACT-B is a self-reported instrument which measures HRQOL of participants with breast cancer. It consists of 5 subscales including physical well-being (PWB), social well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and a breast cancer subscale (BCS). The TOI-PFB score is taken by adding the scores from the PWB (7 items), FWB (7 items), and BCS (9 items) subscales. Items are rated from 0 (not at all) to 4 (very much) and a total score is derived. Scores may range from 0 to 92, with higher scores indicating better HRQOL. A 5 point change has been identified as the clinically minimal important difference (CMID) on the FACT-TOI-PFB scale. The percentage of participants with deterioration was calculated as [number of participants meeting the above threshold divided by the number analyzed] multiplied by 100.	Up to 39 months from randomization until clinical cutoff of 16-Sept-2014 (at Baseline, on Day 1 of Cycles 2 to 8 and every even-numbered cycle thereafter and/or up to 42 days after last dose)
Time to Deterioration in HRQoL as Assessed by FACT-B TOI-PFB Score	The FACT-B is a self-reported instrument which measures HRQOL of participants with breast cancer. It consists of 5 subscales including PWB, SWB, EWB, FWB, and BCS. The TOI-PFB score is taken by adding the scores from the PWB (7 items), FWB (7 items), and BCS (9 items) subscales. Items are rated from 0 (not at all) to 4 (very much) and a total score is derived. Scores may range from 0 to 92, with higher scores indicating better HRQOL. A 5 point change has been identified as the clinically minimal important difference (CMID) on the FACT-TOI-PFB scale. Time to deterioration was defined as the time from Baseline until the first decrease in FACT-B TOI-PFB score. Median time to deterioration was estimated using Kaplan-Meier analysis, and corresponding CIs were computed using the Brookmeyer-Crowley method.	Baseline up to 39 months from randomization until clinical cutoff of 16-Sept-2014
Change From Baseline in Rotterdam Symptom Checklist (RSCL) Activity Level Scale Score	The RSCL is a self-reported instrument which consists of 4 domains including physical symptom distress, psychological distress, activity level, and overall global life quality. Only the activity level scale was collected and assessed. Scores may range from 0 to 100, with higher scores indicating increased burden of disease. Mean RSCL activity scale score changes were calculated as [mean score at the assessment visit minus mean score at Baseline]. The higher the score, the higher the level of impairment or burden.	Baseline, Cycle 7 (Week 18)
Change From Baseline in Work Productivity According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score	The WPAI is a patient-reported measure which assesses the effect of general health and symptom severity on work productivity and regular activities. The General Health questionnaire asks participants to estimate the number of hours missed from work due to reasons related and unrelated to their health problems, as well as the total number of hours actually worked in the preceding 7-day period. The percentage of participants reporting that they were employed (working for pay) was assessed at baseline was assessed along with Absenteeism (work time missed), Presenteeism (impairment at work / reduced on-the-job effectiveness), Work productivity loss (overall work impairment / absenteeism plus presenteeism), and Activity Impairment. The reported changes represent change from baseline at Cycle 7. The score range for the scales of the WPAI is between 0 (no effect) to 100% (max effect)	Baseline, Cycle 7 (Week 18)
Change From Baseline in Activity Impairment According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score	The WPAI is a patient-reported measure which assesses the effect of general health and symptom severity on work productivity and regular activities. The General Health questionnaire asks participants to estimate the number of hours missed from work due to reasons related and unrelated to their health problems, as well as the total number of hours actually worked in the preceding 7-day period. The percentage of participants reporting that they were employed (working for pay) was assessed at baseline was assessed along with Absenteeism (work time missed), Presenteeism (impairment at work / reduced on-the-job effectiveness), Work productivity loss (overall work impairment / absenteeism plus presenteeism), and Activity Impairment. The reported changes represent change from baseline at Cycle 7. The score range for the scales of the WPAI is between 0 (no effect) to 100% (max effect).	Baseline, Cycle 7 (Week 18)
Percentage of Participants With a Best Overall Response of CR or PR According to IRF Assessment Among Those With High Human Epidermal Growth Factor Receptor 2 (HER2) Messenger Ribonucleic Acid (mRNA) Levels	Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. CR was defined as the disappearance of all target and non-target lesions and short-axis reduction in pathological lymph nodes to <10 mm. PR was defined as a ≥30% decrease in sum of diameters of target lesions, taking as reference the Baseline sum. Response was determined using 2 consecutive tumor assessments at least 4 weeks apart. The percentage of participants with a best overall response of CR or PR (ie, the ORR) was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100.	Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
Percentage of Participants With a Best Overall Response of CR or PR According to IRF Assessment Among Those With Low HER2 mRNA Levels	Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. CR was defined as the disappearance of all target and non-target lesions and short-axis reduction in pathological lymph nodes to <10 mm. PR was defined as a ≥30% decrease in sum of diameters of target lesions, taking as reference the Baseline sum. Response was determined using 2 consecutive tumor assessments at least 4 weeks apart. The percentage of participants with a best overall response of CR or PR (ie, the ORR) was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100.	Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With High HER2 mRNA Levels	Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). The percentage of participants with death or disease progression was calculated as [number of participants with event divided by the number analyzed] multiplied by 100.	Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
PFS According to IRF Assessment Among Those With High HER2 mRNA Levels	Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. PFS was defined as the time from randomization to first documented disease progression or death from any cause. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). Median duration of PFS was estimated using Kaplan-Meier analysis.	Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With Low HER2 mRNA Levels	Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). The percentage of participants with death or disease progression was calculated as [number of participants with event divided by the number analyzed] multiplied by 100.	Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
PFS According to IRF Assessment Among Those With Low HER2 mRNA Levels	Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. PFS was defined as the time from randomization to first documented disease progression or death from any cause. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). Median duration of PFS was estimated using Kaplan-Meier analysis.	Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With High HER2 mRNA Levels	The percentage of participants who died prior to clinical cutoff was calculated as [number of participants with event divided by the number analyzed] multiplied by 100.	Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination)
OS at Clinical Cutoff Among Those With High HER2 mRNA Levels	OS was defined as the time from randomization to death from any cause. Median duration of OS was estimated using Kaplan-Meier analysis.	Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination)
Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With Low HER2 mRNA Levels	The percentage of participants who died prior to clinical cutoff was calculated as [number of participants with event divided by the number analyzed] multiplied by 100.	Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination)
OS at Clinical Cutoff Among Those With Low HER2 mRNA Levels	OS was defined as the time from randomization to death from any cause. Median duration of OS was estimated using Kaplan-Meier analysis. Reported upper bound of confidence interval for "Trastuzumab Emtansine + Placebo" and confidence interval values for "Trastuzumab + Taxane" and "Trastuzumab Emtansine + Pertuzumab" are censored values.	Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Collaborators: Genentech, Inc.
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• Perez EA, de Haas SL, Eiermann W, Barrios CH, Toi M, Im YH, Conte PF, Martin M, Pienkowski T, Pivot XB, Burris HA 3rd, Stanzel S, Patre M, Ellis PA. Relationship between tumor biomarkers and efficacy in MARIANNE, a phase III study of trastuzumab emtansine +/- pertuzumab versus trastuzumab plus taxane in HER2-positive advanced breast cancer. BMC Cancer. 2019 May 30;19(1):517. doi: 10.1186/s12885-019-5687-0. Erratum In: BMC Cancer. 2019 Jun 24;19(1):620.
• Bighin C, Pronzato P, Del Mastro L. Trastuzumab emtansine in the treatment of HER-2-positive metastatic breast cancer patients. Future Oncol. 2013 Jul;9(7):955-7. doi: 10.2217/fon.13.74.
• Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nat Rev Cancer. 2012 Mar 22;12(4):278-87. doi: 10.1038/nrc3236.

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2010
• Primary Completion (Actual): September 30, 2014
• Study Completion (Actual): September 16, 2016

Study Registration Dates

• First Submitted: April 28, 2010
• First Submitted That Met QC Criteria: May 7, 2010
• First Posted (Estimated): May 10, 2010

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immunoconjugates; Immunotoxins; Docetaxel; Paclitaxel; Trastuzumab; Maytansine; Ado-Trastuzumab Emtansine; Pertuzumab
• Other Study ID Numbers: BO22589; 2009-017905-13 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No