A Study Of PF-05280014 Or Trastuzumab Plus Taxotere® And Carboplatin In HER2 Positive Breast Cancer In The Neoadjuvant Setting (REFLECTIONS B327-04)

Early Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02187744
• Other study ID #: B3271004
• Secondary ID: REFLECTIONS B327
• Status: Completed
• Phase: Phase 3
• Start date: September 23, 2014
• Est. completion date: March 9, 2016

Study information

• Verified date: December 2018
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 226
• Est. completion date: March 9, 2016
• Est. primary completion date: March 9, 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Early Breast Cancer

Intervention

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.
• 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.

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.

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.
• 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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Belarus,  Czechia,  Hungary,  Italy,  Poland,  Russian Federation,  Serbia,  Slovakia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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