A Study Of PF-05280014 [Trastuzumab-Pfizer] Or Herceptin® [Trastuzumab-EU] Plus Paclitaxel In HER2 Positive First Line Metastatic Breast Cancer Treatment (REFLECTIONS B327-02)

A PHASE 3 RANDOMIZED, DOUBLE-BLIND STUDY OF PF-05280014 PLUS PACLITAXEL VERSUS TRASTUZUMAB PLUS PACLITAXEL FOR THE FIRST-LINE TREATMENT OF PATIENTS WITH HER2-POSITIVE METASTATIC BREAST CANCER

The current study will compare the efficacy, safety, pharmacokinetics and immunogenicity of PF-05280014 in combination with paclitaxel versus trastuzumab sourced from the European Union (trastuzumab-EU) with paclitaxel in female patients with HER2-positive, metastatic breast cancer in the first-line treatment setting. The hypothesis to be tested in this study is that the efficacy (ORR) of PF-05280014 is similar to trastuzumab-EU.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Biological: PF-05280014; Drug: Paclitaxel; Biological: Herceptin®

• Study Type: Interventional
• Enrollment (Actual): 707
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • C.a.b.a, Argentina, C1050AAK
    • Sanatorio de La Providencia
  • Buenos Aires
    • Berazategui, Buenos Aires, Argentina, B1884BBF
      • COIBA - Centro de Oncologia e Investigacion Buenos Aires
  • Santa FE
    • Rosario, Santa FE, Argentina, S2000KZE
      • Instituto de Oncologia de Rosario
  • Tucuman
    • San Miguel de Tucuman, Tucuman, Argentina, T4000IAK
      • Centro Medico San Roque
• Brazil
  • CE
    • Fortaleza, CE, Brazil, 60336-045
      • Crio - Centro Regional Integrado de Oncologia
  • GO
    • Goiania, GO, Brazil, 74605070
      • Associacao de Combate ao Cancer em Goias - Hospital Araujo Jorge
  • Parana
    • Curitiba, Parana, Brazil, 81520-060
      • Liga Paranaense de Combate ao Cancer - Hospital Erasto Gaertner
    • Londrina, Parana, Brazil, 86015-520
      • Instituto do Cancer de Londrina - Hospital do Cancer de Londrina - HCL
  • RIO Grande DO SUL
    • Lajeado, RIO Grande DO SUL, Brazil, 95900-000
      • Hospital Bruno Born (Sociedade Beneficencia e Caridade de Lajeado)
  • RS
    • Ijui, RS, Brazil, 98700-000
      • Associação Hospital de Caridade Ijuí
    • Porto Alegre, RS, Brazil, 90610-000
      • Centro de Pesquisa em Oncologia - Uniao Brasileira de Educacao e Assistencia
  • SAO Paulo
    • Barretos, SAO Paulo, Brazil, 14784-400
      • Fundação Pio XII - Hospital de Câncer de Barretos
  • SC
    • Florianopolis, SC, Brazil, 88034-000
      • Centro de Pesquisas Oncologicas de Santa Catarina - CEPON
    • Itajai, SC, Brazil, 88301-220
      • Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral
  • SP
    • Santo Andre, SP, Brazil, 09060-650
      • CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia - Faculdade de Medicina do ABC
    • Santo Andre, SP, Brazil, 09060-870
      • CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia - Faculdade de Medicina do ABC
  • Santa Catarina
    • Itajai, Santa Catarina, Brazil, 88301-215
      • Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral
• Chile
  • V Region, Chile
    • Hospital Naval Almirante Nef
  • V Region, Chile
    • Instituto Oncologico Clinica Renaca
  • RM
    • Santiago, RM, Chile, 7780050
      • Fresenius Kabi Chile Therapia iv
  • Region DE LA Araucania
    • Temuco, Region DE LA Araucania, Chile, 4810297
      • Clínica Alemana de Temuco
    • Temuco, Region DE LA Araucania, Chile, 4810469
      • Centro de Investigacion Clinica SIM
    • Temuco, Region DE LA Araucania, Chile, 4810561
      • Administrative Office
  • V Region
    • Vina del Mar, V Region, Chile, 2520612
      • Hospital Clínico Viña del Mar
    • Vina del Mar, V Region, Chile, 2540364
      • Instituto Oncologico, Clinica Renaca
• Czechia
  • Praha 2, Czechia, 128 08
    • Onkologicka klinika VFN a 1. LF UK, Fakultni poliklinika
• Greece
  • Athens, Greece, 11527
    • General Hospital of Athens "Hippokration"
  • Crete
    • Chania, Crete, Greece, 73300
      • General Hospital of Chania "O Agios Georgios"
  • Thessaloniki
    • Pylaia, Thessaloniki, Greece, 57001
      • Interbalkan European Medical Center
• Hungary
  • Kecskemet, Hungary, 6000
    • Bacs-Kiskun Megyei Korhaz, Onkoradiologiai Kozpont
  • Miskolc, Hungary, 3526
    • Borsod-Abauj-Zemplen Megyei Korhaz, es Egyetemi Oktatokorhaz, Klinikai Onkologiai es Sugarterapias
  • Szolnok, Hungary, 5000
    • Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz - Rendelointezet, Megyei Onkologiai Kozpont
  • Szombathely, Hungary, 9700
    • Markusovszky Egyetemi Oktatokorhaz
• India
  • Andhra Pradesh
    • Visakhapatnam, Andhra Pradesh, India, 530002
      • Department of Medicine New Block
  • Karnataka
    • Bengaluru, Karnataka, India, 560017
      • Manipal Hospital
    • Manipal, Karnataka, India, 576104
      • Manipal Centre For Clinical Research
  • Maharashtra
    • Mumbai, Maharashtra, India, 400012
      • Tata Memorial Centre, Tata Memorial Hospital
    • Nashik, Maharashtra, India, 422 005
      • Shatabdi Super Speciality Hospital
    • Navi Mumbai, Maharashtra, India, 401210
      • Advanced Centre for Treatment Research and Education in Cancer (ACTREC)
    • Pune, Maharashtra, India, 411004
      • Sahyadri Speciality Hospital
    • Pune, Maharashtra, India, 411 004
      • Deenanath Mangeshkar Hospital & Research Centre
    • Pune, Maharashtra, India, 411004
      • Sahyadri Clinical Research & Development Centre
  • Odisha
    • Cuttack, Odisha, India, 753007
      • Acharya Harihar Regional Cancer Center
  • Rajasthan
    • Bikaner, Rajasthan, India, 334003
      • Acharya Tulsi Regional Cancer Treatment and Research Institute
  • Tamil NADU
    • Madurai, Tamil NADU, India, 625107
      • Meenakshi mission hospital and research centre
  • Telangana
    • Hyderabad, Telangana, India, 500004
      • MNJ Institute of Oncology & Regional Cancer Center
• Japan
  • Chiba, Japan, 260-8717
    • Chiba Cancer Center
  • Kagoshima, Japan, 892-0833
    • Hakuaikai Medical Corporation Sagara Hospital
  • Niigata, Japan, 951-8566
    • Niigata Cancer Center Hospital
  • Osaka, Japan, 553-0003
    • Nakanoshima Osaka Breast Clinic
  • Osaka, Japan, 553-0003
    • Osaka Breast Clinic
  • Shizuoka, Japan, 420-8527
    • Shizuoka General Hospital
  • Aichi
    • Nagoya, Aichi, Japan, 460-0001
      • National Hospital Organization Nagoya Medical Center
  • Fukuoka
    • Fukuoka-Shi, Fukuoka, Japan, 811-1395
      • National Hospital Organization Kyushu Cancer Center
    • Kurume-city, Fukuoka, Japan, 830-0013
      • Japan Community Health care Organization Kurume General Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
  • Kumamoto
    • Kumamoto-city, Kumamoto, Japan, 8608556
      • Kumamoto University Hospital
  • Saitama
    • Kitaadachi-gun, Saitama, Japan, 362-0806
      • Saitama Cancer Center Hospital
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8677
      • Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
    • Meguro-Ku, Tokyo, Japan, 152-8902
      • National Hospital Organization Tokyo Medical Center
    • Shinagawa-ku, Tokyo, Japan, 142-8666
      • Showa University Hospital
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Pusan National University Hospital
  • Daegu, Korea, Republic of, 41404
    • Kyungpook National University Chilgok Hospital
  • Goyang-si, Korea, Republic of, 10408
    • National Cancer Centre
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 08308
    • Korea University Guro Hospital
  • Chungcheongbuk-do
    • Cheongju-si, Chungcheongbuk-do, Korea, Republic of, 28644
      • Chungbuk National University Hospital
  • Korea
    • Ulsan, Korea, Korea, Republic of, 44033
      • Ulsan University Hospital
• Latvia
  • Riga, Latvia, LV 1002
    • P.Stradins Clinical University Hospital
• Mexico
  • Oaxaca, Mexico, 68000
    • Oaxaca Site Management Organization S.C.
  • Queretaro, Mexico, 76090
    • Cancerologia de Queretaro S.C.
  • Distrito Federal
    • Mexico, Distrito Federal, Mexico, 06760
      • Consultorio dentro de la Torre Medica Dalinde (Oncologia Medica)
    • Mexico, Distrito Federal, Mexico, 06760
      • Inter Hosp S.A. de C.V. "Centro Medico Dalinde"
    • Mexico City, Distrito Federal, Mexico, 14080
      • Instituto Nacional de Cancerologia
• Peru
  • Lima, Peru, 34
    • Instituto Nacional de Enfermedades Neoplasicas
  • Lima, Peru, 18
    • Resocentro
  • Lima, Peru, 27
    • Clinica Anglo Americana
  • Lima, Peru, 11
    • Hospital Militar Central
  • Lima, Peru, 11
    • INNPARES
  • Lima, Peru, 27
    • Instituto de Oncologia y Radioterapia de la Clinica Ricardo Palma
  • Lima, Peru, 27
    • Radiologos S.R.L.
  • Lima, Peru, 41
    • Siglo XXI
  • Lima, Peru, Lima 18
    • Resocentro
  • Lima, Peru, Lima 41
    • Siglo XXI
• Philippines
  • Manila, Philippines, 1000
    • Manila Doctors Hospital
  • Cebu
    • Cebu City, Cebu, Philippines, 6000
      • Cebu Doctors' University Hospital
  • Mentro Manila
    • San Juan City, Mentro Manila, Philippines, 1502
      • Cardinal Santos Medical Center
  • Metro Manila
    • Manila, Metro Manila, Philippines, 1000
      • Manila Doctors Hospital
    • Quezon City, Metro Manila, Philippines, 1110
      • Veterans Memorial Medical Center
  • NCR
    • Manila, NCR, Philippines, 1000
      • University of Philippines Manila-Philippine General Hospital
    • Pasig City, NCR, Philippines, 1605
      • The Medical City
    • Quezon City, NCR, Philippines, 1102
      • St. Luke's Medical Center
  • Region VII
    • Cebu City, Region VII, Philippines, 6000
      • The Research Institute at Perpetual Succor Hospital
• Poland
  • Gdansk, Poland, 80-219
    • Copernicus Podmiot Leczniczy Sp. z o.o. Wojewodzkie Centrum Onkologii
  • Gdynia, Poland, 81-519
    • Szpitale Pomorskie Sp. z o.o. Oddzial Onkologii i Radioterapii
  • Lodz, Poland, 90-242
    • Centrum Terapii Wspolczesnej
  • Olsztyn, Poland, 10-228
    • SPZOZ MSW z Warminsko-Mazurskim Centrum Onkologii w Olsztynie, Oddzial Kliniczny Chemioterapii
  • Rzeszow, Poland, 35-085
    • MRUKMED. Lekarz Beata Madej Mruk i Partner. Sp. p. Oddzial nr 1 w Rzeszowie
  • Warszawa, Poland, 03-291
    • Magodent Sp. z o.o. Oddzial Onkologii Klinicznej/Chemioterapii
• Portugal
  • Braga, Portugal, 4710 243
    • Hospital de Braga
  • Lisboa, Portugal, 1998-018
    • Hospital Cuf Descobertas
• Romania
  • Bucuresti, Romania, 050098
    • Spitalul Universitar de Urgenta, Departamentul Oncologie Medicala
  • Sibiu, Romania, 550245
    • Spitalul Clinic Judetean de Urgenta Sibiu
  • Suceava, Romania, 720237
    • Spitalul Judetean de Urgenta "Sf.Ioan cel Nou", Sectia Oncologie
  • Timisoara, Romania, 300595
    • Spitalul Clinic Municipal de Urgenta Timisoara, Sectia Clinica Oncologie Medicala
  • Cluj
    • Cluj-Napoca, Cluj, Romania, 400015
      • Institutul Oncologic Prof. Dr. Ion Chiricuta
    • Cluj-Napoca, Cluj, Romania, 400641
      • S.C. Medisprof S.R.L
  • Dolj
    • Craiova, Dolj, Romania, 200347
      • Centrul de Oncologie Sf. Nectarie
  • Jud Dolj
    • Craiova, Jud Dolj, Romania, 200385
      • SC Oncolab SRL, Oncologie
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • GBUZ Arkhangelsk Regional Clinical Oncological dispensary
  • Chelyabinsk, Russian Federation, 454087
    • State Budgetary Healthcare Institution "Chelyabinsk Regional Clinical Oncological Dispensary"
  • Ivanovo, Russian Federation, 153040
    • "Regional Budgetary Healthcare Institution ""Ivanovo Regional Oncology Dispensary"""
  • Kaluga, Russian Federation, 248007
    • SBIH of Kaluga Region "Kaluga Regional Clinical Oncology Dispensary"
  • Magnitogorsk, Russian Federation, 455001
    • GBUZ "Regional Oncology Dispensary #2"
  • Moscow, Russian Federation, 115478
    • Federal State Budgetary Institution "Russian Oncological Scientific Center n.a. N.N. Blokhin" of
  • Moscow, Russian Federation, 121309
    • LLC VitaMed
  • Moscow, Russian Federation, 129515
    • LLC VitaMed
  • Nizhniy Novgorod, Russian Federation, 603081
    • State Budgetary Healthcare Institution "Nizhniy Novgorod Regional Oncological Dispensary"
  • Omsk, Russian Federation, 644046
    • "BIH of Omsk Region ""Clinical oncological dispensary"""
  • Orel, Russian Federation, 302020
    • Budgetary Institution of Healthcare of Orel region "Orel oncological dispensary"
  • Ryazan, Russian Federation, 390011
    • SBEI HPE RyazSMU of MoH of the Russian Federation based on SBI of Ryazan Region "Regional CLinical
  • Saint Petersburg, Russian Federation, 197022
    • SBEI of HPE "First Saint Petersburg State Medical University
  • Saint-Petersburg, Russian Federation, 196247
    • Saint-Petersburg State Budgetary Healthcare Institution "Oncological Dispensary of Moscow District"
  • Saint-Petersburg, Russian Federation, 195067
    • SBI "North-Western State Medical University n.a. I. I. Mechnikov" of the MoH of the Russian
  • Saint-Petersburg, Russian Federation, 195271
    • Non-state healthcare agency Road Clinical Hospital PLC Russian Railways
  • Saratov, Russian Federation, 410004
    • Non-State Healthcare Institution "Road Clinical Hospital at Saratov II Station"
  • Stavropol, Russian Federation, 355047
    • State Budgetary Healthcare Institution of Stavropol region "Stavropol regional clinical oncology
  • Chechenkaya Republic
    • Grozny, Chechenkaya Republic, Russian Federation, 364020
      • Republic Clinical Hospital of Emergency Care
  • Kursk
    • Kislino Settlement, Kursk, Russian Federation, 305524
      • State Healthcare Institution Kursk Regional Oncological Dispensary of the Healthcare Committee
  • Leningrad Region
    • Kuzmolovo, Vsevolozhskiy, Leningrad Region, Russian Federation, 188663
      • State Budgetary Healthcare Institution "Leningrad Regional Oncological Dispensary"
  • NAP
    • Moscow, NAP, Russian Federation, 115478
      • FSBSI Russian Cancer Research Center n.a. N.N.Blokhin
    • Perm, NAP, Russian Federation, 614066
      • GBUZ of Perm region "Perm regional oncology dispensary"
  • Pos.pesochny
    • Saint-Petersburg, Pos.pesochny, Russian Federation, 197758
      • Federal State Budgetary Institution ¿National Medical Research Oncology Centre named after N.N.
  • Republic OF Bashkortostan
    • Ufa, Republic OF Bashkortostan, Russian Federation, 450054
      • State Healthcare Institution, Republican Clinical Oncology Dispensary of the Ministry of
  • Republic OF Baskortostan
    • Ufa, Republic OF Baskortostan, Russian Federation, 450005
      • GBUZ Republican Clinical Hospital n.a. G.F. Kuvatova
    • Ufa, Republic OF Baskortostan, Russian Federation, 450054
      • Republican Clinical Oncology Dispensary of the Ministry of Healthcare of Baskortostan Republic
  • Republic OF Karelia
    • Petrozavodsk, Republic OF Karelia, Russian Federation, 185002
      • State Budgetary Healthcare Institution ''Republic Oncological Dispensary''
  • Republic OF Mordovia
    • Saransk, Republic OF Mordovia, Russian Federation, 430032
      • State budget institution of healthcare of Mordovia Republic "Republic Oncology Dispensary"
  • Rostov Region
    • Rostov-on-Don, Rostov Region, Russian Federation, 344037
      • Rostov Research Institute of Oncology
  • Saint Petersburg
    • Pushkin, Saint Petersburg, Russian Federation, 196603
      • Private Medical Institution Euromedservice
  • Saint-petersburg
    • Poselok Pesochny, Saint-petersburg, Russian Federation, 197758
      • Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology)
  • Stavropol Region
    • Kislovodsk, Stavropol Region, Russian Federation, 357700
      • LLC Medekspert
    • Lermontov, Stavropol Region, Russian Federation, 357340
      • Federal State Budgetary Healthcare Institution of "Clinical Hospital #101 of Federal Medical and
    • Pyatigorsk, Stavropol Region, Russian Federation, 357502
      • Centre of Specialized kinds of Medical Care of Pyatigorsk city
    • Pyatigorsk, Stavropol Region, Russian Federation, 357502
      • State Budgetary Healthcare Institution of Stavropol Region Pyatigorsk Oncology Dispensary
    • Pyatigorsk, Stavropol Region, Russian Federation, 357519
      • LLC Novaya Clinica
    • Pyatigorsk, Stavropol Region, Russian Federation, 357538
      • Pyatigorsk City Hospital #2
    • Pyatigorsk, Stavropol Region, Russian Federation, 357563
      • Stavropol Regional Hospital for War Veterans
  • Volgograd Region
    • Volzhskiy, Volgograd Region, Russian Federation, 404130
      • State Budgetary Healthcare Institution Volgograd Regional Clinical Oncology Dispensary
• Serbia
  • Belgrade, Serbia, 11000
    • Military Medical Academy
  • Belgrade, Serbia, 11000
    • Institute for Oncology and Radiology of Serbia
  • Nis, Serbia, 18000
    • Clinic of Oncology-Clinical Center Nis
  • Sremska Kamenica, Serbia, 21204
    • Oncology Institute of Vojvodina
• Slovakia
  • Bratislava, Slovakia, 833 10
    • Narodny onkologicky ustav
  • Bratislava, Slovakia, 812 50
    • Onkologicky ustav sv. Alzbety, s.r.o.
• South Africa
  • Eastern CAPE
    • Port Elizabeth, Eastern CAPE, South Africa, 6045
      • GVI Oncology, Langenhoven Drive Oncology Centre
  • Gauteng
    • Joannesburg, Gauteng, South Africa, 2193
      • Wits Clinical Research
    • Johannesburg, Gauteng, South Africa, 2196
      • The Medical Oncology Centre of Rosebank
    • Johannesburg, Gauteng, South Africa, 2199
      • Sandton Oncology Centre
    • Pretoria, Gauteng, South Africa, 0002
      • *Department of Medical Oncology, University of Pretoria & Steve Biko Academic Hospitals Complex
    • Pretoria, Gauteng, South Africa, 0081
      • Eastleigh Breast Care Centre
  • Western CAPE
    • Kraaifontein, Western CAPE, South Africa, 7570
      • Cape Town Oncology Trials
    • Rondebosch, Western CAPE, South Africa, 7700
      • GVI Rondebosch Oncology Centre-Rondebosch Medical Centre
• Thailand
  • Bangkok, Thailand, 10330
    • Faculty of Medicine, Chulongkorn University, Medical Oncology Unit
  • Bangkok
    • Ratchathewi, Bangkok, Thailand, 10400
      • National Cancer Institute
  • Udonthani
    • Amphur Muang, Udonthani, Thailand, 41330
      • Udonthani Cancer Hospital
• Turkey
  • Adana, Turkey, 01120
    • Baskent University School of Medicine Adana Hospital
  • Ankara, Turkey, 06100
    • Hacettepe Universitesi Tip Fakultesi
  • Bursa, Turkey, 16059
    • Uludag Universitesi Tip Fakultesi Ic Hastaliklari Anabilim Dali
  • Diyarbakir, Turkey, 21080
    • Dicle University Medical Faculty
  • Gaziantep, Turkey, 27310
    • Gaziantep University Medical Faculty
  • Istanbul, Turkey, 34093
    • Istanbul Universitesi Onkoloji Enstitusu
• Ukraine
  • Chernivtsi, Ukraine, 58013
    • Municipal Institution "Chernivtsi Regional Clinical Oncology Center", Outpatient Department
  • Dnipro, Ukraine, 49102
    • Municipal Non-Profit Enterprise City Clinical Hospital No.4of Dnipro Regional Council, Department of
  • Kharkiv, Ukraine, 61070
    • Communal Non-Profit Enterprise "Regional Center of Oncology"
  • Kharkiv, Ukraine, 61024
    • SI Institute of Medical Radiology n.a.S.P. Ilrygoriev of National Academy of Medical Science of
  • Khmelnytskyi, Ukraine, 29009
    • Khmelnytskyi Regional Oncologic Dispensary
  • Kryvyi Rih, Ukraine, 50048
    • Municipal Enterprise 'Kryvyi Rih Oncology Dispensary of Dnipropetrovsk Regional Council'
  • Kyiv, Ukraine, 04107
    • Municipal Non-Profit Enterprise of Kyiv Regional Council "Kyiv Regional Oncology Dispensary"
  • Lviv, Ukraine, 79031
    • Lviv State Oncologic Regional Treatment and Diagnostic Center
  • Odesa, Ukraine, 65025
    • Municipal Institution Odesa Regional Clinical Hospital, Mammology Center
  • Uzhgorod, Ukraine, 88014
    • Zakarpattia Regional Clinical Oncological Center
  • Vinnytsia, Ukraine, 21029
    • Municipal Non-profit Enterprise Podilsk Regional Oncology Centre of Vinnytsia Regional Council
• United States
  • Connecticut
    • Plainville, Connecticut, United States, 06062
      • Cancer Center of Central Connecticut
    • Southington, Connecticut, United States, 06489
      • Cancer Center of Central Connecticut
  • Florida
    • Boca Raton, Florida, United States, 33428
      • Florida Cancer Research Institute
    • Plantation, Florida, United States, 33324
      • Florida Cancer Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of breast cancer.
• Presence of metastatic disease.
• Documentation of HER2 gene amplification or overexpression.
• Available tumor tissue for central review of HER2 status.
• At least 1 measurable lesion as defined by RECIST 1.1.
• Eastern Cooperative Oncology Group status of 0 to 2.
• Left ventricular ejection fraction within institutional range of normal, measured by either two dimensional echocardiogram or multigated acquisition scan.

Exclusion Criteria:

• Relapse within 1 year of last dose of previous adjuvant (including neoadjuvant) treatment (except endocrine therapy) and within 1 year before randomization.
• Prior systemic therapy for metastatic disease (except endocrine therapy).
• Prior cumulative dose of doxorubicin of >400 mg/m2, epirubicin dose >800 mg/m^2, or the equivalent dose for other anthracyclines or derivatives (eg, 72 mg/m^2 of mitoxantrone). If the patient has received more than one anthracycline, then the cumulative dose must not exceed the equivalent of 400 mg/m^2 of doxorubicin.
• Inflammatory breast cancer.
• Active uncontrolled or symptomatic central nervous system metastases.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PF-05280014	Biological: PF-05280014; Concentrate for solution for infusion, sterile vial 150 mg. Initial dose of 4 mg/kg over 90 minutes (depending on tolerability) IV infusion, then 2 mg/kg over 30 to 90 minutes (depending on tolerability) IV infusion until disease progression. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 regimen may be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.; Other Names: Trastuzumab-Pfizer; Drug: Paclitaxel; A nonaqueous solution intended for dilution with a suitable parenteral fluid prior to intravenous infusion. Paclitaxel is available in 30 mg (5 mL), 100 mg (16.7 mL), and 300 mg (50 mL) multidose vials. Each mL of sterile nonpyrogenic solution contains 6 mg paclitaxel. The starting dose of paclitaxel will be 80 mg/m^2 by IV infusion over 60 minutes (duration of infusion may be modified according to local standard of care, if applicable). Provision is made for dose reduction to 70 mg/m^2 and then 60 mg/m^2 as needed. In the absence of disease progression in the judgment of the investigator or prohibitive toxicity, patients will receive treatment with paclitaxel for at least 6 cycles or until maximal benefit of response is obtained, in the judgment of the investigator.
ACTIVE_COMPARATOR: Herceptin®	Drug: Paclitaxel; A nonaqueous solution intended for dilution with a suitable parenteral fluid prior to intravenous infusion. Paclitaxel is available in 30 mg (5 mL), 100 mg (16.7 mL), and 300 mg (50 mL) multidose vials. Each mL of sterile nonpyrogenic solution contains 6 mg paclitaxel. The starting dose of paclitaxel will be 80 mg/m^2 by IV infusion over 60 minutes (duration of infusion may be modified according to local standard of care, if applicable). Provision is made for dose reduction to 70 mg/m^2 and then 60 mg/m^2 as needed. In the absence of disease progression in the judgment of the investigator or prohibitive toxicity, patients will receive treatment with paclitaxel for at least 6 cycles or until maximal benefit of response is obtained, in the judgment of the investigator.; Biological: Herceptin®; Concentrate for solution for infusion, sterile vial 150 mg. Initial dose of 4 mg/kg over 90 minutes (depending on tolerability) IV infusion, then 2 mg/kg over 30 to 90 minutes (depending on tolerability) IV infusion weekly until disease progression. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the Herceptin® regimen may be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.; Other Names: Trastuzumab (EU)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Derived From Central Radiology Assessments: ITT Population	ORR was defined as the percentage of participants who achieved complete response (CR, complete disappearance of all target lesions with the exception of nodal disease; all target nodes must have decreased to normal size [short axis <10 mm]) or partial response (PR, >=30% decrease from baseline of the sum of diameters (SOD) of all target measurable lesions; the short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions) by Week 25 of the study and confirmed on a follow-up assessment (Week 33+/-14 days), based on the assessments of the central radiology review in accordance with RECIST 1.1.	From the date of randomization until all participants had either completed the Week 33 tumor assessment or discontinued study drug earlier than the Week 33 visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
One-year Progression-Free Survival (PFS) Rate Derived From Central Radiology Assessments: ITT Population	One-year PFS rate was analyzed based on the time from date of randomization to first documentation of progressive disease (PD), or death due to any cause in the absence of documented PD, based on the assessments of the central radiology review in accordance with RECIST 1.1. PD was defined for target disease as at least a 20% increase in sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy) with a minimum absolute increase of 5 mm. For non-target disease: PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion was also considered PD. The 95% CI for the median time to event was based on the Brookmeyer and Crowley method.	From the date of randomization until 378 days post-randomization
Duration of Response (DOR) Per Central Radiology Assessments: ITT Population	DOR:time from first documentation of objective response (CR or PR) to first documentation of PD/death due to any cause in absence of documented PD, based on central radiology review. As per RECIST v1.1, CR:complete disappearance of all target lesions with exception of nodal disease; all target nodes reduced in short axis <10 mm. PR: >=30% decrease from baseline of SOD of target lesions; short diameter used in sum for target nodes,longest diameter used in sum for other target lesions. PD for target disease:at least 20% increase in SOD of target lesions above smallest sum observed (over baseline if no decrease in sum observed) with minimum absolute increase of 5 mm. For non-target disease:unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion was also considered PD. The 95% CI for median time to event was based on the Brookmeyer and Crowley method.	From the date of randomization until 378 days post-randomization
Overall Survival: ITT Population	Overall survival was analyzed based on the time from date of randomization to the date of death due to any cause. Participants last known to be alive were censored on the date of last contact. The 95% CI for the median time to event was based on the Brookmeyer and Crowley Method.	From the date of randomization until end of study (approximately 6 years)
Serum Peak Concentration of PF-05280014 at Selected Cycles: Pharmacokinetics (PK) Population	Human PK serum samples were analyzed for concentrations of PF-05280014 using a validated, sensitive, and specific enzyme-linked immunosorbent assay (ELISA).	1 hour post end of infusion on Day 1 of Cycles 1 and 5
Serum Peak Concentration of Trastuzumab-EU at Selected Cycles: PK Population	Human PK serum samples were analyzed for concentrations of trastuzumab-EU using a validated, sensitive, and specific ELISA.	1 hour post end of infusion on Day 1 of Cycles 1 and 5
Serum Trough (Pre-dose) Concentration of PF-05280014 at Selected Cycles: PK Population	Human PK serum samples were analyzed for concentrations of PF-05280014 using a validated, sensitive, and specific ELISA.	Pre-dose on Day 1 of Cycles 1, 3, 4, 5, 7, 8, 11, 14, 17 and Day 8 of Cycles 1 and 5
Serum Trough (Pre-dose) Concentration of Trastuzumab-EU at Selected Cycles: PK Population	Human PK serum samples were analyzed for concentrations of trastuzumab-EU using a validated, sensitive, and specific ELISA.	Pre-dose on Day 1 of Cycles 1, 3, 4, 5, 7, 8, 11, 14, 17 and Day 8 of Cycles 1 and 5
Number of Participants With Positive Anti-Drug Antibodies (ADA) Sample: Safety Population	Two sensitive, specific, and semi-quantitative electrochemiluminescent (ECL) immunoassays, 1 for detecting antibodies against PF-05280014 and the other for detecting antibodies against trastuzumab, were used to analyze ADA samples. Serum samples were first screened for ADA. Any samples that were positive in the screening assay were further analyzed to confirm the positive result and determine the antibody titers. All samples were taken prior to dosing. The number of participants with a positive sample (titer >=1.0) is provided.	Pre-dose on Day 1 of Cycles 1, 3, 5, 8, 11, 14, 17
Number of Participants With Positive Neutralizing Antibodies (Nab) Prior to Treatment: Safety Population	Human serum samples testing positive for the presence of ADA (anti-PF-05280014 or anti-trastuzumab-EU) were analyzed for the presence or absence of NAb (neutralizing anti-PF-05280014 or neutralizing anti-trastuzumab-EU antibodies) following a tiered approach using screening and titer determination. The number of participants at baseline (prior to treatment) with a positive NAb sample (titer >=1.48) is provided.	Cycle 1 Day 1 (prior to treatment)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Li RK, Tokunaga E, Adamchuk H, Vladimirov V, Yanez E, Lee KS, Bondarenko I, Vana A, Hilton F, Ishikawa T, Tajima K, Lipatov O. Long-Term Safety and Effectiveness of PF-05280014 (a Trastuzumab Biosimilar) Treatment in Patients with HER2-Positive Metastatic Breast Cancer: Updated Results of a Randomized, Double-Blind Study. BioDrugs. 2022 Jan;36(1):55-69. doi: 10.1007/s40259-021-00513-7. Epub 2022 Feb 8.
• Chen X, Li C, Ewesuedo R, Yin D. Population pharmacokinetics of PF-05280014 (a trastuzumab biosimilar) and reference trastuzumab (Herceptin(R)) in patients with HER2-positive metastatic breast cancer. Cancer Chemother Pharmacol. 2019 Jul;84(1):83-92. doi: 10.1007/s00280-019-03850-1. Epub 2019 May 3. Erratum In: Cancer Chemother Pharmacol. 2019 Sep;84(3):667.
• Pegram MD, Bondarenko I, Zorzetto MMC, Hingmire S, Iwase H, Krivorotko PV, Lee KS, Li RK, Pikiel J, Aggarwal R, Ewesuedo R, Freyman A, Li R, Vana A, Yin D, Zacharchuk C, Tan-Chiu E. PF-05280014 (a trastuzumab biosimilar) plus paclitaxel compared with reference trastuzumab plus paclitaxel for HER2-positive metastatic breast cancer: a randomised, double-blind study. Br J Cancer. 2019 Jan;120(2):172-182. doi: 10.1038/s41416-018-0340-2. Epub 2018 Dec 20.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 24, 2014
• Primary Completion (ACTUAL): August 24, 2016
• Study Completion (ACTUAL): June 27, 2020

Study Registration Dates

• First Submitted: October 28, 2013
• First Submitted That Met QC Criteria: November 14, 2013
• First Posted (ESTIMATE): November 21, 2013

Study Record Updates

• Last Update Posted (ACTUAL): July 6, 2021
• Last Update Submitted That Met QC Criteria: June 7, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: trastuzumab; Breast Neoplasms; Phase 3
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Paclitaxel; Trastuzumab; Albumin-Bound Paclitaxel
• Other Study ID Numbers: B3271002 (OTHER: Alias Study Number); REFLECTIONS B327-02; 2013-001352-34 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.