A Study Of PF-05280014 Or Trastuzumab Plus Taxotere® And Carboplatin In HER2 Positive Breast Cancer In The Neoadjuvant Setting (REFLECTIONS B327-04)
A RANDOMIZED, DOUBLE-BLIND PHARMACOKINETIC STUDY OF PF-05280014 PLUS TAXOTERE (REGISTERED) AND CARBOPLATIN VERSUS HERCEPTIN (REGISTERED) PLUS TAXOTERE (REGISTERED) AND CARBOPLATIN FOR THE NEOADJUVANT TREATMENT OF PATIENTS WITH OPERABLE HER2-POSITIVE BREAST CANCER
4 other identifiers
interventional
226
10 countries
52
Brief Summary
The current study will compare PK, efficacy, safety, and immunogenicity of PF-05280014 (Trastuzumab-Pfizer) in combination with Taxotere® and Carboplatin (Paraplatin) versus Herceptin® (Trastuzumab-EU) approved in the EU in combination with Taxotere® and Carboplatin (Paraplatin) in patients with operable HER2 positive, breast cancer in the neoadjuvant setting. The hypothesis to be tested in this study is the percentage of patients with steady state Cycle 5 Ctrough (Cycle 6 pre-dose) \>20 µg/mL of trastuzumab-Pfizer is similar to EU-approved trastuzumab, using a margin of -12.5%.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Sep 2014
52 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 30, 2014
CompletedFirst Posted
Study publicly available on registry
July 11, 2014
CompletedStudy Start
First participant enrolled
September 23, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 9, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
March 9, 2016
CompletedResults Posted
Study results publicly available
April 7, 2017
CompletedJanuary 8, 2019
December 1, 2018
1.5 years
June 30, 2014
February 22, 2017
December 19, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants With Steady State Drug Concentration Ctrough (Cycle 6 Pre-dose) >20 µg/mL at Cycle 5.
The percentage of participants with Cycle 5 Ctrough (Cycle 6 pre-dose) \>20 μg/mL in each treatment group, the denominator being the number of participants in the per protocol population for each treatment group.
Cycle 5
Secondary Outcomes (5)
Mean Predose Trastuzumab-Pfizer and Trastuzumab-EU Concentrations at Cycles 1 Through 6.
Cycles 1 through 6
Pathologic Complete Response (pCR) Defined as the Absence of Invasive Neoplastic Cells in the Breast and Lymph Nodes.
Cycle 6/End of treatment
Objective Response Rate (ORR) Defined as the Percentage of Participants Having Complete or Partial Response at End of Treatment, Based on Radiographic Assessments of the Tumor.
Cycle 6/End of treatment
Incidence of Anti-trastuzumab Antibodies (ADAs) at Cycles 1 Through 6.
Cycles 1 through 6
Incidence of Neutralizing Antibodies (NAb) at Cycles 1 Through 6.
Cycles 1 through 6
Study Arms (2)
PF-05280014
EXPERIMENTALHerceptin®
ACTIVE COMPARATORInterventions
Concentrate for solution for infusion, sterile vial 150 mg, Day 1 Cycle 1 will be a loading dose of 8 mg/kg infused over 90 minutes. Subsequent infusions will follow every 3 weeks (i.e., cycled every 21 days) with a dose of 6 mg/kg administered over 30 to 90 minutes depending on tolerability, maximum of 6 cycles.
Injection concentrate single-dose vials containing 20 mg (0.5 mL) or 80 mg (2 mL), each mL contains 40 mg docetaxel (anhydrous) and 1040 mg polysorbate 80, The starting dose of Taxotere® (docetaxel) will be 75 mg/m2 administered intravenously over 60 minutes every three weeks on Day 1 of each cycle (i.e., every 21 days), maximum 6 cycles.
Lyophilized powder, single-dose vials containing 50 mg, 150 mg, and 450 mg of Carboplatin for administration by intravenous infusion (each vial contains equal parts by weight of Carboplatin and mannitol), starting dose 6 AUC, over 15 minutes or longer every three weeks on Day 1 of each cycle (i.e., every 21 days), maximum 6 cycles.
Concentrate for solution for infusion, sterile vial 150 mg, Day 1 Cycle 1 will be a loading dose of 8 mg/kg infused over 90 minutes. Subsequent infusions will follow every 3 weeks (i.e., cycled every 21 days) with a dose of 6 mg/kg administered over 30 to 90 minutes depending on tolerability, maximum 6 cycles.
Eligibility Criteria
You may qualify if:
- Histologically confirmed HER2 overexpressing invasive breast cancer.
- Plan for definitive surgical resection of breast tumor (i.e., lumpectomy or mastectomy, and sentinel node (SN) biopsy or axillary lymph node dissection (ALND).
- Plan for neoadjuvant chemotherapy.
- Measurable disease in the breast after diagnostic biopsy, defined as longest diameter ≥ 2.0 cm.
You may not qualify if:
- Bilateral breast cancer.
- Inflammatory breast cancer.
- Presence of known distant metastases.
- Received prior treatment, including chemotherapy, endocrine therapy, biologic therapy, radiation or surgery with the exception of diagnostic biopsy for primary breast cancer.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
Study Sites (52)
Compassionate Cancer Care Medical Group, Inc.
Fountain Valley, California, 92708, United States
Millennium Oncology (Imaging Facility)
Kingwood, Texas, 77339, United States
Millennium Oncology (Imaging Facility)
Shenandoah, Texas, 77380, United States
Millennium Oncology
Shenandoah, Texas, 77384, United States
SI 'Republican Research and Practice Centre of Oncology and Medical Radiology n.a. N.N. Alexandrov'
Lyasny, Minsk Oblast, 223040, Belarus
Fakultni nemocnice Hradec Kralove
Hradec Králové, 500 05, Czechia
Bacs-Kiskun Megyei Korhaz
Kecskemét, Bács-Kiskun county, 6000, Hungary
Semmelweis Egyetem Altalanos Orvostudomanyi Kar-I. sz. Belgyogyaszati Klinika Onkologiai Reszleg
Budapest, 1083, Hungary
Szent Imre Egyetemi Oktato Korhaz
Budapest, 1115, Hungary
Uzsoki Utcai Korhaz, Onkoradiologia, Sugarterapia Fovarosi Onkoradiologiai Kozpont
Budapest, 1145, Hungary
Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktatokorhaz,
Miskolc, 3526, Hungary
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz - Rendelointezet
Szolnok, 5000, Hungary
Division of Medical Senology
Milan, MI, 20141, Italy
Divisione di Oncologia Medica B
Roma, RM, 00144, Italy
IRCCS Istituto Nazionale Tumori Regina Elena (IRE)
Roma, RM, 00144, Italy
Dept. of Surgery
Roma, RM, 00168, Italy
Szpitale Wojewodzkie w Gdyni Sp. z o.o., Oddzial Onkoligii i Radioterapii
Gdynia, 81-519, Poland
Oddzial Chorob Rozrostowych
Lodz, 93-513, Poland
SPZOZ MSW z Warminsko-Mazurskim Centrum Onkologii w Olsztynie
Olsztyn, 10-228, Poland
State Budgetary Healthcare Institution "Leningrad Regional Oncological Dispensary"
Kuzmolovo, Leningradskaya Oblast', 188663, Russia
"State Budgetary Healthcare Institution ""Republican Clinical Oncological Dispensary of the Ministry
Ufa, Republic Bashkortost, 450054, Russia
Regional Budgetary Healthcare Institution "Kursk regional clinical oncological Dispensary"
Kislino Settlement, Ryshkovskiy Village Council, 305524, Russia
"State Budgetary Healthcare Institution of Stavropol Region ""Pyatigorsk Oncological Dispensary"""
Pyatigorsk, Stavropol Kray, 357502, Russia
State Budgetary Healthcare Institution "Volgograd Regional Oncological Dispensary #3"
Volzhsky, Volgograd Oblast, 404130, Russia
SBHI "Regional Oncology Dispensary"
Irkutsk, 664035, Russia
Regional Budgetary Healthcare Institution
Kursk, 305035, Russia
FSBI "Russian Oncology Scientific center n.a. N. N. Blokhin" RAMS
Moscow, 115478, Russia
State Budgetary Institution Of Healthcare
Moscow, 129301, Russia
SBHI of NNR "Clinical diagnostic center"
Nizhny Novgorod, 603006, Russia
State Budgetary Healthcare Institution of NNR "Nizhniy Novgorod Regional Oncological Dispensary"
Nizhny Novgorod, 603081, Russia
Budgetary Institution of healthcare of Omsk region "Clinical oncological dispensary"
Omsk, 644046, Russia
State Budgetary Educational Institution of Higher Professional Education "North-Western State
Saint Petersburg, 195067, Russia
Saint-Peterbsurg Clinical Oncological dispensary of Moscow district
Saint Petersburg, 196247, Russia
Saint-Petersburg State Budgetary Healthcare Institution "Oncological Dispensary of Moscow District"
Saint Petersburg, 196247, Russia
LLC RAMSAY Diagnostic RUS
Saint Petersburg, 197046, Russia
"Federal State Institution ""Scientific Research Institute of Oncology n.a. N.N.Petrov""
Saint Petersburg, 197758, Russia
Saint-Petersburg State Budgetary Institution of healthcare "City Clinical Oncological Dispensary"
Saint Petersburg, 198255, Russia
SRBHI "Regional Clinical Oncology Dispensary"
Veliky Novgorod, 173023, Russia
Institute For Oncology And Radiology Of Serbia
Belgrade, 11000, Serbia
Onkologicky ustav sv. Alzbety, s.r.o.
Bratislava, 812 50, Slovakia
Narodny Onkologicky ustav
Bratislava, 833 10, Slovakia
Vychodoslovensky onkologicky ustav, a.s.
Košice, 04191, Slovakia
Municipal Healthcare Institution 'Chernihiv Regional Oncology Dispensary', Mamology Department
Chernihiv, 14029, Ukraine
MI 'City Dnipropetrovsk Multi-field Clin. Hospital #4 of DRC', Dep.-nt of Chemotherapy;
Dnipropetrovsk, 49102, Ukraine
SI "Institute of Medical Radiology n.a.S.P. Hrygoriev of National Academy
Kharkiv, 61024, Ukraine
Munincipal Healthcare Institution"Kharkiv Regional Clinical Oncologic Center
Kharkiv, 61070, Ukraine
Khmelnytskyi Regional Oncologic Dispensary
Khmelnytskyi, 29009, Ukraine
MI 'Kryvyi Rih Oncology Dispensary of Dnipropetrovsk Regional Council'
Kryvyi Rih, 50048, Ukraine
Lviv State Oncologic Regional Treatment and Diagnostic Center
Lviv, 79031, Ukraine
Municipal Institution 'Odesa Regional Clinical Hospital', Mamology Center
Odesa, 65025, Ukraine
Regional Municipal Institution "Sumy Regional Clinical Oncology Dispensary", Thoracic Department
Sumy, 40005, Ukraine
Vinnytsia Regional Oncology Clinical Dispensary, Chemotherapy Department
Vinnytsia, 21029, Ukraine
Related Publications (1)
Lammers PE, Dank M, Masetti R, Abbas R, Hilton F, Coppola J, Jacobs I. Neoadjuvant PF-05280014 (a potential trastuzumab biosimilar) versus trastuzumab for operable HER2+ breast cancer. Br J Cancer. 2018 Aug;119(3):266-273. doi: 10.1038/s41416-018-0147-1. Epub 2018 Jul 13.
PMID: 30002437DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
It was decided that the secondary study objective to explore the relationship between drug exposure and pCR for PF-05280014 versus trastuzumab-EU would not be analyzed.
Results Point of Contact
- Title
- Pfizer CT.gov Call Center
- Organization
- Pfizer, Inc.
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 30, 2014
First Posted
July 11, 2014
Study Start
September 23, 2014
Primary Completion
March 9, 2016
Study Completion
March 9, 2016
Last Updated
January 8, 2019
Results First Posted
April 7, 2017
Record last verified: 2018-12
Data Sharing
- IPD Sharing
- Will share
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.