Clinical trial NCT02187744: A Study Of PF-05280014 Or Trastuzumab Plus Taxotere® And Carboplatin In HER2 Positive Breast Cancer In The Neoadjuvant Setting (REFLECTIONS B327-04)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Early Breast Cancer
Keywords: Biosimilars
Non-inferiority
Neoadjuvant Setting
Early Breast Cancer
PK
Phase 3
Trastuzumab
Herceptin
HER2 Positive
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2014-07-11
Enrollment: 226
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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%.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Steady State Drug Concentration Ctrough (Cycle 6 Pre-dose) >20 µg/mL at Cycle 5.
timeFrame: Cycle 5
Secondary outcomes:
measure: Mean Predose Trastuzumab-Pfizer and Trastuzumab-EU Concentrations at Cycles 1 Through 6.
timeFrame: Cycles 1 through 6
measure: Pathologic Complete Response (pCR) Defined as the Absence of Invasive Neoplastic Cells in the Breast and Lymph Nodes.
timeFrame: Cycle 6/End of treatment
measure: 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.
timeFrame: Cycle 6/End of treatment
measure: Incidence of Anti-trastuzumab Antibodies (ADAs) at Cycles 1 Through 6.
timeFrame: Cycles 1 through 6
measure: Incidence of Neutralizing Antibodies (NAb) at Cycles 1 Through 6.
timeFrame: Cycles 1 through 6
Other outcomes:
Locations:
city: Fountain Valley
country: United States
facility: Compassionate Cancer Care Medical Group, Inc.
state: California
city: Kingwood
country: United States
facility: Millennium Oncology (Imaging Facility)
state: Texas
city: Shenandoah
country: United States
facility: Millennium Oncology (Imaging Facility)
state: Texas
city: Shenandoah
country: United States
facility: Millennium Oncology
state: Texas
city: Lesnoy
country: Belarus
facility: SI 'Republican Research and Practice Centre of Oncology and Medical Radiology n.a. N.N. Alexandrov'
state: Minsk Region
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Kecskemet
country: Hungary
facility: Bacs-Kiskun Megyei Korhaz
state: Bacs-kiskun
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Altalanos Orvostudomanyi Kar-I. sz. Belgyogyaszati Klinika Onkologiai Reszleg
city: Budapest
country: Hungary
facility: Szent Imre Egyetemi Oktato Korhaz
city: Budapest
country: Hungary
facility: Uzsoki Utcai Korhaz, Onkoradiologia, Sugarterapia Fovarosi Onkoradiologiai Kozpont
city: Miskolc
country: Hungary
facility: Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktatokorhaz,
city: Szolnok
country: Hungary
facility: Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz - Rendelointezet
city: Milano
country: Italy
facility: Division of Medical Senology
state: MI
city: Roma
country: Italy
facility: Divisione di Oncologia Medica B
state: RM
city: Roma
country: Italy
facility: IRCCS Istituto Nazionale Tumori Regina Elena (IRE)
state: RM
city: Roma
country: Italy
facility: Dept. of Surgery
state: RM
city: Gdynia
country: Poland
facility: Szpitale Wojewodzkie w Gdyni Sp. z o.o., Oddzial Onkoligii i Radioterapii
city: Lodz
country: Poland
facility: Oddzial Chorob Rozrostowych
city: Olsztyn
country: Poland
facility: SPZOZ MSW z Warminsko-Mazurskim Centrum Onkologii w Olsztynie
city: Kuzmolovo
country: Russian Federation
facility: State Budgetary Healthcare Institution "Leningrad Regional Oncological Dispensary"
state: Leningrad Region
city: Ufa
country: Russian Federation
facility: "State Budgetary Healthcare Institution ""Republican Clinical Oncological Dispensary of the Ministry
state: Republic Bashkortost
city: Kislino Settlement
country: Russian Federation
facility: Regional Budgetary Healthcare Institution "Kursk regional clinical oncological Dispensary"
state: Ryshkovskiy Village Council
city: Pyatigorsk
country: Russian Federation
facility: State Budgetary Healthcare Institution of Stavropol Region "Pyatigorsk Oncological Dispensary"
state: Stavropol Region
city: Volzhskiy
country: Russian Federation
facility: State Budgetary Healthcare Institution "Volgograd Regional Oncological Dispensary #3"
state: Volgograd Region
city: Irkutsk
country: Russian Federation
facility: SBHI "Regional Oncology Dispensary"
city: Kursk
country: Russian Federation
facility: Regional Budgetary Healthcare Institution
city: Moscow
country: Russian Federation
facility: FSBI "Russian Oncology Scientific center n.a. N. N. Blokhin" RAMS
city: Moscow
country: Russian Federation
facility: State Budgetary Institution Of Healthcare
city: Nizhniy Novgorod
country: Russian Federation
facility: SBHI of NNR "Clinical diagnostic center"
city: Nizhniy Novgorod
country: Russian Federation
facility: State Budgetary Healthcare Institution of NNR "Nizhniy Novgorod Regional Oncological Dispensary"
city: Omsk
country: Russian Federation
facility: Budgetary Institution of healthcare of Omsk region "Clinical oncological dispensary"
city: Saint-Petersburg
country: Russian Federation
facility: State Budgetary Educational Institution of Higher Professional Education "North-Western State
city: Saint-Petersburg
country: Russian Federation
facility: Saint-Peterbsurg Clinical Oncological dispensary of Moscow district
city: Saint-Petersburg
country: Russian Federation
facility: Saint-Petersburg State Budgetary Healthcare Institution "Oncological Dispensary of Moscow District"
city: Saint-Petersburg
country: Russian Federation
facility: LLC RAMSAY Diagnostic RUS
city: Saint-Petersburg
country: Russian Federation
facility: "Federal State Institution ""Scientific Research Institute of Oncology n.a. N.N.Petrov""
city: Saint-Petersburg
country: Russian Federation
facility: Saint-Petersburg State Budgetary Institution of healthcare "City Clinical Oncological Dispensary"
city: Velikiy Novgorod
country: Russian Federation
facility: SRBHI "Regional Clinical Oncology Dispensary"
city: Belgrade
country: Serbia
facility: Institute For Oncology And Radiology Of Serbia
city: Bratislava
country: Slovakia
facility: Onkologicky ustav sv. Alzbety, s.r.o.
city: Bratislava
country: Slovakia
facility: Narodny Onkologicky ustav
city: Kosice
country: Slovakia
facility: Vychodoslovensky onkologicky ustav, a.s.
city: Chernihiv
country: Ukraine
facility: Municipal Healthcare Institution 'Chernihiv Regional Oncology Dispensary', Mamology Department
city: Dnipropetrovsk
country: Ukraine
facility: MI 'City Dnipropetrovsk Multi-field Clin. Hospital #4 of DRC', Dep.-nt of Chemotherapy;
city: Kharkiv
country: Ukraine
facility: SI "Institute of Medical Radiology n.a.S.P. Hrygoriev of National Academy
city: Kharkiv
country: Ukraine
facility: Munincipal Healthcare Institution"Kharkiv Regional Clinical Oncologic Center
city: Khmelnytskyi
country: Ukraine
facility: Khmelnytskyi Regional Oncologic Dispensary
city: Kryvyi Rih
country: Ukraine
facility: MI 'Kryvyi Rih Oncology Dispensary of Dnipropetrovsk Regional Council'
city: Lviv
country: Ukraine
facility: Lviv State Oncologic Regional Treatment and Diagnostic Center
city: Odesa
country: Ukraine
facility: Municipal Institution 'Odesa Regional Clinical Hospital', Mamology Center
city: Sumy
country: Ukraine
facility: Regional Municipal Institution "Sumy Regional Clinical Oncology Dispensary", Thoracic Department
city: Vinnytsia
country: Ukraine
facility: Vinnytsia Regional Oncology Clinical Dispensary, Chemotherapy Department
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.