Metastatic Breast CancerPhase 3NCT01989676
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 study testing PF-05280014, Paclitaxel and Herceptin® in people with Metastatic Breast Cancer, run by Pfizer at 188 sites in 24 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- PF-05280014, Paclitaxel and Herceptin®
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 707 participants
- Where
- 188 sitesin 24 countries
- Study dates
- 24 Feb 2014to 27 Jun 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
188 sites in 24 countries.
188 sites in 24 countries
Russia40 sites
GBUZ Arkhangelsk Regional Clinical Oncological dispensary
Arkhangelsk, 163045
State Budgetary Healthcare Institution "Chelyabinsk Regional Clinical Oncological Dispensary"
Chelyabinsk, 454087
Republic Clinical Hospital of Emergency Care
Grozny, Chechenkaya Republic, 364020
"Regional Budgetary Healthcare Institution ""Ivanovo Regional Oncology Dispensary"""
Ivanovo, 153040
SBIH of Kaluga Region "Kaluga Regional Clinical Oncology Dispensary"
Kaluga, 248007
State Healthcare Institution Kursk Regional Oncological Dispensary of the Healthcare Committee
Kislino Settlement, Kursk Oblast, 305524
LLC Medekspert
Kislovodsk, Stavropol Kray, 357700
State Budgetary Healthcare Institution "Leningrad Regional Oncological Dispensary"
Kuzmolovo, Vsevolozhskiy, Leningradskaya Oblast', 188663
Federal State Budgetary Healthcare Institution of "Clinical Hospital #101 of Federal Medical and
Lermontov, Stavropol Kray, 357340
GBUZ "Regional Oncology Dispensary #2"
Magnitogorsk, 455001
FSBSI Russian Cancer Research Center n.a. N.N.Blokhin
Moscow, NAP, 115478
Federal State Budgetary Institution "Russian Oncological Scientific Center n.a. N.N. Blokhin" of
Moscow, 115478
LLC VitaMed
Moscow, 121309
LLC VitaMed
Moscow, 129515
State Budgetary Healthcare Institution "Nizhniy Novgorod Regional Oncological Dispensary"
Nizhny Novgorod, 603081
"BIH of Omsk Region ""Clinical oncological dispensary"""
Omsk, 644046
Budgetary Institution of Healthcare of Orel region "Orel oncological dispensary"
Oryol, 302020
GBUZ of Perm region "Perm regional oncology dispensary"
Perm, NAP, 614066
State Budgetary Healthcare Institution ''Republic Oncological Dispensary''
Petrozavodsk, Republic of Karelia, 185002
Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology)
Poselok Pesochny, Sankt-Peterburg, 197758
Private medical institution Euromedservice
Pushkin, Sankt-Peterburg, 196603
Centre of Specialized kinds of Medical Care of Pyatigorsk city
Pyatigorsk, Stavropol Kray, 357502
State Budgetary Healthcare Institution of Stavropol Region Pyatigorsk Oncology Dispensary
Pyatigorsk, Stavropol Kray, 357502
LLC Novaya Clinica
Pyatigorsk, Stavropol Kray, 357519
Pyatigorsk City Hospital #2
Pyatigorsk, Stavropol Kray, 357538
Stavropol Regional Hospital for War Veterans
Pyatigorsk, Stavropol Kray, 357563
Rostov Research Institute of Oncology
Rostov-on-Don, Rostov Oblast, 344037
SBEI HPE RyazSMU of MoH of the Russian Federation based on SBI of Ryazan Region "Regional CLinical
Ryazan, 390011
Federal State Budgetary Institution ¿National Medical Research Oncology Centre named after N.N.
Saint Petersburg, Pos.pesochny, 197758
SBI "North-Western State Medical University n.a. I. I. Mechnikov" of the MoH of the Russian
Saint Petersburg, 195067
Non-state healthcare agency Road Clinical Hospital PLC Russian Railways
Saint Petersburg, 195271
Saint-Petersburg State Budgetary Healthcare Institution "Oncological Dispensary of Moscow District"
Saint Petersburg, 196247
SBEI of HPE "First Saint Petersburg State Medical University
Saint Petersburg, 197022
State budget institution of healthcare of Mordovia Republic "Republic Oncology Dispensary"
Saransk, Respublika Mordoviya, 430032
Non-State Healthcare Institution "Road Clinical Hospital at Saratov II Station"
Saratov, 410004
State Budgetary Healthcare Institution of Stavropol region "Stavropol regional clinical oncology
Stavropol, 355047
GBUZ Republican Clinical Hospital n.a. G.F. Kuvatova
Ufa, Bashkortostan Republic, 450005
Republican Clinical Oncology Dispensary of the Ministry of Healthcare of Baskortostan Republic
Ufa, Bashkortostan Republic, 450054
State Healthcare Institution, Republican Clinical Oncology Dispensary of the Ministry of
Ufa, Bashkortostan Republic, 450054
State Budgetary Healthcare Institution Volgograd Regional Clinical Oncology Dispensary
Volzhsky, Volgograd Oblast, 404130
Japan15 sites
Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
Bunkyo-ku, Tokyo, 113-8677
Chiba Cancer Center
Chiba, 260-8717
National Hospital Organization Kyushu Cancer Center
Fukuoka, Fukuoka, 811-1395
Hakuaikai Medical Corporation Sagara Hospital
Kagoshima, 892-0833
Saitama Cancer Center Hospital
Kitaadachi-gun, Saitama, 362-0806
Kumamoto University Hospital
Kumamoto, Kumamoto, 8608556
Japan Community Health care Organization Kurume General Hospital
Kurume, Fukuoka, 830-0013
National Hospital Organization Tokyo Medical Center
Meguro-Ku, Tokyo, 152-8902
National Hospital Organization Nagoya Medical Center
Nagoya, Aichi-ken, 460-0001
Niigata Cancer Center Hospital
Niigata, 951-8566
Nakanoshima Osaka Breast Clinic
Osaka, 553-0003
Osaka Breast Clinic
Osaka, 553-0003
Hokkaido University Hospital
Sapporo, Hokkaido, 060-8648
Showa University Hospital
Shinagawa-ku, Tokyo, 142-8666
Shizuoka General Hospital
Shizuoka, 420-8527
Brazil13 sites
Fundacao Pio XII - Hospital de Cancer de Barretos
Barretos, São Paulo, 14784-400
Liga Paranaense de Combate ao Cancer - Hospital Erasto Gaertner
Curitiba, Paraná, 81520-060
Centro de Pesquisas Oncologicas de Santa Catarina - CEPON
Florianópolis, Santa Catarina, 88034-000
CRIO - Centro Regional Integrado de Oncologia
Fortaleza, Ceará, 60336-045
Associacao de Combate ao Cancer em Goias - Hospital Araujo Jorge
Goiânia, Goiás, 74605070
Associacao Hospital de Caridade Ijui
Ijuí, Rio Grande do Sul, 98700-000
Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral
Itajaí, Santa Catarina, 88301-215
Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral
Itajaí, Santa Catarina, 88301-220
Hospital Bruno Born (Sociedade Beneficencia e Caridade de Lajeado)
Lajeado, Rio Grande do Sul, 95900-000
Instituto do Cancer de Londrina - Hospital do Cancer de Londrina - HCL
Londrina, Paraná, 86015-520
Centro de Pesquisa em Oncologia - Uniao Brasileira de Educacao e Assistencia
Porto Alegre, Rio Grande do Sul, 90610-000
CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia - Faculdade de Medicina do ABC
Santo André, São Paulo, 09060-650
CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia - Faculdade de Medicina do ABC
Santo André, São Paulo, 09060-870
India13 sites
Manipal Hospital
Bengaluru, Karnataka, 560017
Acharya Tulsi Regional Cancer Treatment and Research Institute
Bikaner, Rajasthan, 334003
Acharya Harihar Regional Cancer Center
Cuttack, Odisha, 753007
MNJ Institute of Oncology & Regional Cancer Center
Hyderabad, Telangana, 500004
Meenakshi Mission Hospital and Research Centre
Madurai, Tamil Nadu, 625107
Manipal Centre for Clinical Research
Manipal, Karnataka, 576104
Tata Memorial Centre, Tata Memorial Hospital
Mumbai, Maharashtra, 400012
Shatabdi Super Speciality Hospital
Nashik, Maharashtra, 422 005
Advanced Centre for Treatment Research and Education in Cancer (ACTREC)
Navi Mumbai, Maharashtra, 401210
Deenanath Mangeshkar Hospital & Research Centre
Pune, Maharashtra, 411 004
Sahyadri Clinical Research & Development Centre
Pune, Maharashtra, 411004
Sahyadri Speciality Hospital
Pune, Maharashtra, 411004
Department of Medicine New Block
Visakhapatnam, Andhra Pradesh, 530002
Ukraine11 sites
Municipal Institution "Chernivtsi Regional Clinical Oncology Center", Outpatient Department
Chernivtsi, 58013
Municipal Non-Profit Enterprise City Clinical Hospital No.4of Dnipro Regional Council, Department of
Dnipro, 49102
SI Institute of Medical Radiology n.a.S.P. Ilrygoriev of National Academy of Medical Science of
Kharkiv, 61024
Communal Non-Profit Enterprise "Regional Center of Oncology"
Kharkiv, 61070
Khmelnytskyi Regional Oncologic Dispensary
Khmelnytskyi, 29009
Municipal Enterprise 'Kryvyi Rih Oncology Dispensary of Dnipropetrovsk Regional Council'
Kryvyi Rih, 50048
Municipal Non-Profit Enterprise of Kyiv Regional Council "Kyiv Regional Oncology Dispensary"
Kyiv, 04107
Lviv State Oncologic Regional Treatment and Diagnostic Center
Lviv, 79031
Municipal Institution Odesa Regional Clinical Hospital, Mammology Center
Odesa, 65025
Zakarpattia Regional Clinical Oncological Center
Uzhhorod, 88014
Municipal Non-profit Enterprise Podilsk Regional Oncology Centre of Vinnytsia Regional Council
Vinnytsia, 21029
Peru10 sites
Hospital Militar Central
Lima, 11
INNPARES
Lima, 11
Resocentro
Lima, 18
Clinica Anglo Americana
Lima, 27
Instituto de Oncologia y Radioterapia de la Clinica Ricardo Palma
Lima, 27
Radiologos S.R.L.
Lima, 27
Instituto Nacional de Enfermedades Neoplasicas
Lima, 34
Siglo XXI
Lima, 41
Resocentro
Lima, Lima 18
Siglo XXI
Lima, Lima 41
Philippines9 sites
Cebu Doctors' University Hospital
Cebu City, CEBU, 6000
The Research Institute at Perpetual Succor Hospital
Cebu City, Central Visayas, 6000
Manila Doctors Hospital
Manila, National Capital Region, 1000
University of Philippines Manila-Philippine General Hospital
Manila, NCR, 1000
Manila Doctors Hospital
Manila, 1000
The Medical City
Pasig, NCR, 1605
Veterans Memorial Medical Center
Quezon City, National Capital Region, 1110
St. Luke's Medical Center
Quezon City, NCR, 1102
Cardinal Santos Medical Center
San Juan City, Mentro Manila, 1502
Chile8 sites
Fresenius Kabi Chile Therapia iv
Santiago, RM, 7780050
Clinica Alemana de Temuco
Temuco, Araucania, 4810297
Centro de Investigacion Clinica SIM
Temuco, Araucania, 4810469
Administrative office
Temuco, Araucania, 4810561
Hospital Naval Almirante Nef
V Region
Instituto Oncologico Clinica Renaca
V Region
Hospital Clinico Vina Del Mar
Viña del Mar, Valparaiso, 2520612
Instituto Oncologico, Clinica Renaca
Viña del Mar, Valparaiso, 2540364
Romania8 sites
Spitalul Universitar de Urgenta, Departamentul Oncologie Medicala
Bucharest, 050098
Institutul Oncologic Prof. Dr. Ion Chiricuta
Cluj-Napoca, Cluj, 400015
S.C. Medisprof S.R.L
Cluj-Napoca, Cluj, 400641
Centrul de Oncologie Sf. Nectarie
Craiova, Dolj, 200347
SC Oncolab SRL, Oncologie
Craiova, JUD DOLJ, 200385
Spitalul Clinic Judetean de Urgenta Sibiu
Sibiu, 550245
Spitalul Judetean de Urgenta "Sf.Ioan cel Nou", Sectia Oncologie
Suceava, 720237
Spitalul Clinic Municipal de Urgenta Timisoara, Sectia Clinica Oncologie Medicala
Timișoara, 300595
South Africa8 sites
wits Clinical Research
Joannesburg, Gauteng, 2193
The Medical Oncology Centre of Rosebank
Johannesburg, Gauteng, 2196
Sandton Oncology Centre
Johannesburg, Gauteng, 2199
Cape Town Oncology Trials
Kraaifontein, Western Cape, 7570
GVI Oncology, Langenhoven Drive Oncology Centre
Port Elizabeth, Eastern Cape, 6045
*Department of Medical Oncology, University of Pretoria & Steve Biko Academic Hospitals Complex
Pretoria, Gauteng, 0002
Eastleigh Breast Care Centre
Pretoria, Gauteng, 0081
GVI Rondebosch Oncology Centre-Rondebosch Medical Centre
Rondebosch, Western Cape, 7700
South Korea8 sites
Pusan National University Hospital
Busan, 49241
Chungbuk National University Hospital
Cheongju-si, North Chungcheong, 28644
Kyungpook National University Chilgok Hospital
Daegu, 41404
National Cancer Centre
Goyang-si, 10408
Korea University Anam Hospital
Seoul, 02841
Severance Hospital, Yonsei University Health System
Seoul, 03722
Korea University Guro Hospital
Seoul, 08308
Ulsan University Hospital
Ulsan, Korea, 44033
Poland6 sites
COPERNICUS Podmiot Leczniczy Sp. z o.o. Wojewodzkie Centrum Onkologii
Gdansk, 80-219
Szpitale Pomorskie Sp. z o.o. Oddzial Onkologii i Radioterapii
Gdynia, 81-519
Centrum Terapii Wspolczesnej
Lodz, 90-242
SPZOZ MSW z Warminsko-Mazurskim Centrum Onkologii w Olsztynie, Oddzial Kliniczny Chemioterapii
Olsztyn, 10-228
MRUKMED. Lekarz Beata Madej Mruk i Partner. Sp. p. Oddzial nr 1 w Rzeszowie
Rzeszów, 35-085
Magodent Sp. z o.o. Oddzial Onkologii Klinicznej/Chemioterapii
Warsaw, 03-291
Turkey (Türkiye)6 sites
Baskent University School of Medicine Adana Hospital
Adana, 01120
Hacettepe Universitesi Tip Fakultesi
Ankara, 06100
Uludag Universitesi Tip Fakultesi Ic Hastaliklari Anabilim Dali
Bursa, 16059
Dicle University Medical Faculty
Diyarbakır, 21080
Gaziantep University Medical Faculty
Gaziantep, 27310
Istanbul Universitesi Onkoloji Enstitusu
Istanbul, 34093
Mexico5 sites
Consultorio dentro de la Torre Medica Dalinde (Oncologia Medica)
Mexico City, Mexico City, 06760
Inter Hosp S.A. de C.V. "Centro Medico Dalinde"
Mexico City, Mexico City, 06760
Instituto Nacional de Cancerologia
Mexico City, Mexico City, 14080
Oaxaca Site Management Organization S.C.
Oaxaca City, 68000
Cancerologia de Queretaro S.C.
Querétaro, 76090
United States4 sites
Florida Cancer Research Institute
Boca Raton, Florida, 33428
Cancer Center of Central Connecticut
Plainville, Connecticut, 06062
Florida Cancer Research Institute
Plantation, Florida, 33324
Cancer Center of Central Connecticut
Southington, Connecticut, 06489
Argentina4 sites
COIBA - Centro de Oncologia e Investigacion Buenos Aires
Berazategui, Buenos Aires, B1884BBF
Sanatorio de la Providencia
C.a.b.a, C1050AAK
Instituto De Oncologia De Rosario
Rosario, Santa Fe Province, S2000KZE
Centro Medico San Roque
San Miguel de Tucumán, Tucumán Province, T4000IAK
Hungary4 sites
Bacs-Kiskun Megyei Korhaz, Onkoradiologiai Kozpont
Kecskemét, 6000
Borsod-Abauj-Zemplen Megyei Korhaz, es Egyetemi Oktatokorhaz, Klinikai Onkologiai es Sugarterapias
Miskolc, 3526
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz - Rendelointezet, Megyei Onkologiai Kozpont
Szolnok, 5000
Markusovszky Egyetemi Oktatokorhaz
Szombathely, 9700
Serbia4 sites
Institute for Oncology and Radiology of Serbia
Belgrade, 11000
Military Medical Academy
Belgrade, 11000
Oncology Institute of Vojvodina
Kamenitz, 21204
Clinic of Oncology-Clinical Center Nis
Niš, 18000
Greece3 sites
General Hospital of Athens "Hippokration"
Athens, 11527
General Hospital of Chania "O Agios Georgios"
Chania, Crete, 73300
Interbalkan European Medical Center
Pylaia, Thessaloniki, 57001
Thailand3 sites
Udonthani Cancer Hospital
Amphur Muang, Udonthani, 41330
Faculty of Medicine, Chulongkorn University, Medical Oncology Unit
Bangkok, 10330
National Cancer Institute
Ratchathewi, Bangkok, 10400
Portugal2 sites
Hospital de Braga
Braga, 4710 243
Hospital CUF Descobertas
Lisbon, 1998-018
Slovakia2 sites
Onkologicky ustav sv. Alzbety, s.r.o.
Bratislava, 812 50
Narodny Onkologicky Ustav
Bratislava, 833 10
Czechia1 site
Onkologicka klinika VFN a 1. LF UK, Fakultni poliklinika
Prague, 128 08
About this study
Official title: 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.
- Conditions
- Metastatic Breast Cancer
- Being tested
- PF-05280014, Paclitaxel, Herceptin®
- Keywords
- Phase 3, trastuzumab, Breast Neoplasms
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-05280014Biological
Also called Trastuzumab-Pfizer
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.
PaclitaxelDrug
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.
Herceptin®Biological
Also called Trastuzumab (EU)
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.
PaclitaxelDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| PF-05280014 | Experimental | Not described Receives: Biological: PF-05280014; Drug: Paclitaxel |
| Herceptin® | Active comparator | Not described Receives: Biological: Herceptin®; Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 outcomes (9)
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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Cycle 1 Day 1 (prior to treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2013 (estimated)
- Study start24 Feb 2014
- Primary completion24 Aug 2016
- Study completion27 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 707 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01989676
- Sponsor's protocol ID
- B3271002
- Other IDs
- REFLECTIONS B327-02, 2013-001352-34, B3271002
- Status last verified
- Jun 2021
- First submitted
- 28 Oct 2013
- Last updated
- 6 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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.
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.
PubMed 35133617Chen 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.
PubMed 31053945Pegram 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.
PubMed 30568294
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01989676
- Acronym / sponsor ID
- B3271002
- Conditions
- Metastatic Breast Cancer
- Keywords
- Phase 3, trastuzumab, Breast Neoplasms
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 707 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 24 Feb 2014 (actual)
- Primary completion
- 24 Aug 2016 (actual)
- Study completion
- 27 Jun 2020 (actual)
- First posted
- 21 Nov 2013 (estimated)
- Results
- Posted 23 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PF-05280014 | Experimental | Biological: PF-05280014, Drug: Paclitaxel |
| Herceptin® | Active comparator | Biological: Herceptin®, Drug: Paclitaxel |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PF-05280014Also: Trastuzumab-PfizerConcentrate 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. | Biological | PF-05280014 |
| PaclitaxelA 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. | Drug | PF-05280014 |
| Herceptin®Also: Trastuzumab (EU)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. | Biological | Herceptin® |
| PaclitaxelA 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. | Drug | Herceptin® |
Primary outcome
Objective Response Rate (ORR) Derived From Central Radiology Assessments: ITT Population
Time frame: 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
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.
9 secondary outcomes
One-year Progression-Free Survival (PFS) Rate Derived From Central Radiology Assessments: ITT Population
Time frame: From the date of randomization until 378 days post-randomization
Duration of Response (DOR) Per Central Radiology Assessments: ITT Population
Time frame: From the date of randomization until 378 days post-randomization
Overall Survival: ITT Population
Time frame: From the date of randomization until end of study (approximately 6 years)
Serum Peak Concentration of PF-05280014 at Selected Cycles: Pharmacokinetics (PK) Population
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Cycle 1 Day 1 (prior to treatment)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35133617Li 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.
- Derived from this study: PubMed 31053945Chen 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.
- Derived from this study: PubMed 30568294Pegram 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.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
188 sites in 24 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing PF-05280014, Paclitaxel and Herceptin® in people with Metastatic Breast Cancer, run by Pfizer at 188 sites in 24 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 188 sites in Russia, Japan, Brazil, India, Ukraine and 19 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) Derived From Central Radiology Assessments: ITT Population (time frame: 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01989676, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2021.