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

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%.

Study Overview

• Status: Completed
• Conditions: Early Breast Cancer
• Intervention / Treatment: Biological: PF-05280014; Drug: Taxotere®; Drug: Paraplatin®; Biological: Trastuzumab-EU

• Study Type: Interventional
• Enrollment (Actual): 226
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belarus
  • Minsk Region
    • Lesnoy, Minsk Region, Belarus, 223040
      • SI 'Republican Research and Practice Centre of Oncology and Medical Radiology n.a. N.N. Alexandrov'
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove
• Hungary
  • Budapest, Hungary, 1115
    • Szent Imre Egyetemi Oktato Korhaz
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem Altalanos Orvostudomanyi Kar-I. sz. Belgyogyaszati Klinika Onkologiai Reszleg
  • Budapest, Hungary, 1145
    • Uzsoki Utcai Korhaz, Onkoradiologia, Sugarterapia Fovarosi Onkoradiologiai Kozpont
  • Miskolc, Hungary, 3526
    • Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktatokorhaz,
  • Szolnok, Hungary, 5000
    • Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz - Rendelointezet
  • Bacs-kiskun
    • Kecskemet, Bacs-kiskun, Hungary, 6000
      • Bacs-Kiskun Megyei Korhaz
• Italy
  • MI
    • Milano, MI, Italy, 20141
      • Division of Medical Senology
  • RM
    • Roma, RM, Italy, 00144
      • Divisione di Oncologia Medica B
    • Roma, RM, Italy, 00144
      • IRCCS Istituto Nazionale Tumori Regina Elena (IRE)
    • Roma, RM, Italy, 00168
      • Dept. of Surgery
• Poland
  • Gdynia, Poland, 81-519
    • Szpitale Wojewodzkie w Gdyni Sp. z o.o., Oddzial Onkoligii i Radioterapii
  • Lodz, Poland, 93-513
    • Oddzial Chorob Rozrostowych
  • Olsztyn, Poland, 10-228
    • SPZOZ MSW z Warminsko-Mazurskim Centrum Onkologii w Olsztynie
• Russian Federation
  • Irkutsk, Russian Federation, 664035
    • SBHI "Regional Oncology Dispensary"
  • Kursk, Russian Federation, 305035
    • Regional Budgetary Healthcare Institution
  • Moscow, Russian Federation, 115478
    • FSBI "Russian Oncology Scientific center n.a. N. N. Blokhin" RAMS
  • Moscow, Russian Federation, 129301
    • State Budgetary Institution Of Healthcare
  • Nizhniy Novgorod, Russian Federation, 603006
    • SBHI of NNR "Clinical diagnostic center"
  • Nizhniy Novgorod, Russian Federation, 603081
    • State Budgetary Healthcare Institution of NNR "Nizhniy Novgorod Regional Oncological Dispensary"
  • Omsk, Russian Federation, 644046
    • Budgetary Institution of healthcare of Omsk region "Clinical oncological dispensary"
  • Saint-Petersburg, Russian Federation, 195067
    • State Budgetary Educational Institution of Higher Professional Education "North-Western State
  • Saint-Petersburg, Russian Federation, 196247
    • Saint-Peterbsurg Clinical Oncological dispensary of Moscow district
  • Saint-Petersburg, Russian Federation, 196247
    • Saint-Petersburg State Budgetary Healthcare Institution "Oncological Dispensary of Moscow District"
  • Saint-Petersburg, Russian Federation, 197046
    • LLC RAMSAY Diagnostic RUS
  • Saint-Petersburg, Russian Federation, 197758
    • "Federal State Institution ""Scientific Research Institute of Oncology n.a. N.N.Petrov""
  • Saint-Petersburg, Russian Federation, 198255
    • Saint-Petersburg State Budgetary Institution of healthcare "City Clinical Oncological Dispensary"
  • Velikiy Novgorod, Russian Federation, 173023
    • SRBHI "Regional Clinical Oncology Dispensary"
  • Leningrad Region
    • Kuzmolovo, Leningrad Region, Russian Federation, 188663
      • State Budgetary Healthcare Institution "Leningrad Regional Oncological Dispensary"
  • Republic Bashkortost
    • Ufa, Republic Bashkortost, Russian Federation, 450054
      • "State Budgetary Healthcare Institution ""Republican Clinical Oncological Dispensary of the Ministry
  • Ryshkovskiy Village Council
    • Kislino Settlement, Ryshkovskiy Village Council, Russian Federation, 305524
      • Regional Budgetary Healthcare Institution "Kursk regional clinical oncological Dispensary"
  • Stavropol Region
    • Pyatigorsk, Stavropol Region, Russian Federation, 357502
      • "State Budgetary Healthcare Institution of Stavropol Region ""Pyatigorsk Oncological Dispensary"""
  • Volgograd Region
    • Volzhskiy, Volgograd Region, Russian Federation, 404130
      • State Budgetary Healthcare Institution "Volgograd Regional Oncological Dispensary #3"
• Serbia
  • Belgrade, Serbia, 11000
    • Institute for Oncology and Radiology of Serbia
• Slovakia
  • Bratislava, Slovakia, 833 10
    • Narodny onkologicky ustav
  • Bratislava, Slovakia, 812 50
    • Onkologicky ustav sv. Alzbety, s.r.o.
  • Kosice, Slovakia, 04191
    • Vychodoslovensky onkologicky ustav, a.s.
• Ukraine
  • Chernihiv, Ukraine, 14029
    • Municipal Healthcare Institution 'Chernihiv Regional Oncology Dispensary', Mamology Department
  • Dnipropetrovsk, Ukraine, 49102
    • MI 'City Dnipropetrovsk Multi-field Clin. Hospital #4 of DRC', Dep.-nt of Chemotherapy;
  • Kharkiv, Ukraine, 61024
    • SI "Institute of Medical Radiology n.a.S.P. Hrygoriev of National Academy
  • Kharkiv, Ukraine, 61070
    • Munincipal Healthcare Institution"Kharkiv Regional Clinical Oncologic Center
  • Khmelnytskyi, Ukraine, 29009
    • Khmelnytskyi Regional Oncologic Dispensary
  • Kryvyi Rih, Ukraine, 50048
    • MI 'Kryvyi Rih Oncology Dispensary of Dnipropetrovsk Regional Council'
  • Lviv, Ukraine, 79031
    • Lviv State Oncologic Regional Treatment and Diagnostic Center
  • Odesa, Ukraine, 65025
    • Municipal Institution 'Odesa Regional Clinical Hospital', Mamology Center
  • Sumy, Ukraine, 40005
    • Regional Municipal Institution "Sumy Regional Clinical Oncology Dispensary", Thoracic Department
  • Vinnytsia, Ukraine, 21029
    • Vinnytsia Regional Oncology Clinical Dispensary, Chemotherapy Department
• United States
  • California
    • Fountain Valley, California, United States, 92708
      • Compassionate Cancer Care Medical Group, Inc.
  • Texas
    • Kingwood, Texas, United States, 77339
      • Millennium Oncology (Imaging Facility)
    • Shenandoah, Texas, United States, 77384
      • Millennium Oncology
    • Shenandoah, Texas, United States, 77380
      • Millennium Oncology (Imaging Facility)

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 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• 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, 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.; Drug: Taxotere®; 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.; Other Names: docetaxel; Drug: Paraplatin®; 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.; Other Names: carboplatin
Active Comparator: Herceptin®	Drug: Taxotere®; 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.; Other Names: docetaxel; Drug: Paraplatin®; 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.; Other Names: carboplatin; Biological: Trastuzumab-EU; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Predose Trastuzumab-Pfizer and Trastuzumab-EU Concentrations at Cycles 1 Through 6.	Samples of blood were taken pre-dose on Cycles 1, 2, 4, 5, and 6, and at 1 hour post dose on Cycles 1 and 5 for pharmacokinetic evaluation.	Cycles 1 through 6
Pathologic Complete Response (pCR) Defined as the Absence of Invasive Neoplastic Cells in the Breast and Lymph Nodes.	Following surgery after treatment completion, tumors were assessed as Complete Pathological Response, Partial Pathological Response, or No Pathological Response.	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.	ORR was defined as Complete Response (CR), Partial Response (PR), Stable (SD), Progressive Disease (PD) or Indeterminate (IND). ORR was the percentage of participants who had CR or PR at Cycle 6/End of treatment.	Cycle 6/End of treatment
Incidence of Anti-trastuzumab Antibodies (ADAs) at Cycles 1 Through 6.	The number of participants with positive (titer >=1.00) pre-dose ADA samples, participants counted towards the total if for at least one sample, the ADA was positive.	Cycles 1 through 6
Incidence of Neutralizing Antibodies (NAb) at Cycles 1 Through 6.	The number of participants with positive (NAb response >=1.48) pre-dose NAb samples, participants counted towards the total if for at least one sample, the NAb was positive.	Cycles 1 through 6

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• 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.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2014
• Primary Completion (Actual): March 9, 2016
• Study Completion (Actual): March 9, 2016

Study Registration Dates

• First Submitted: June 30, 2014
• First Submitted That Met QC Criteria: July 8, 2014
• First Posted (Estimate): July 11, 2014

Study Record Updates

• Last Update Posted (Actual): January 8, 2019
• Last Update Submitted That Met QC Criteria: December 19, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: PK; HER2 Positive; Trastuzumab; Phase 3; Herceptin; Non-inferiority; Early Breast Cancer; Biosimilars; Neoadjuvant Setting
• 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, Immunological; Docetaxel; Carboplatin; Trastuzumab
• Other Study ID Numbers: B3271004; REFLECTIONS B327-04; 2013-004679-11 (EudraCT Number); REFLECTIONS (B327-04) (Other Identifier: Alias Study 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.