Clinical trial NCT01901146: Efficacy and Safety Study of ABP 980 Compared With Trastuzumab in Women With HER2-positive Early Breast Cancer
Official title: A Randomized, Double-Blind, Phase 3 Study Evaluating the Efficacy and Safety of ABP 980 Compared With Trastuzumab in Subjects With HER2 Positive Early Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: Human Epidermal Growth Factor Receptor 2 (HER2)
Positive Early Breast Cancer
Lead sponsor: Amgen
Sponsor class: INDUSTRY
Collaborators: name: Actavis Inc.
First posted: 2013-07-17
Enrollment: 725
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 purpose of this research study is to compare the effectiveness and safety of ABP 980 against trastuzumab in women with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer.


Eligibility criteria: Inclusion Criteria:

* Females ≥ 18 years of age
* Histologically confirmed invasive breast cancer
* Planning for surgical resection of breast tumor and sentinel node or axillary lymph node resection
* Planning neoadjuvant chemotherapy
* HER2 positive disease
* Measurable disease in the breast after diagnostic biopsy, defined as longest diameter ≥ 2.0 cm
* Known estrogen receptor (ER) and progesterone receptor (PR) hormone receptor status at study entry
* Normal bone marrow function
* Normal hepatic function
* Normal renal function
* Subjects must sign an Institutional Review Board/Ethics Committee (IRB/EC)-approved informed consent form before any study specific procedures

Inclusion Criteria for Randomization:

* Left ventricular ejection fraction (LVEF) of ≥55% by 2D echocardiogram
* Complete all 4 cycles of run-in chemotherapy

Exclusion Criteria:

* Bilateral breast cancer
* Presence of known metastases
* Received prior treatment, including chemotherapy, biologic therapy, radiation or surgery with the exception of diagnostic biopsy for primary breast cancer
* Other concomitant active malignancy or history of malignancy in the past 5 years except treated basal cell carcinoma of the skin or carcinoma in situ of the cervix
* Pre-existing clinically significant (≥ grade 2) peripheral neuropathy
* Any history of documented or current congestive heart failure, current high-risk uncontrolled arrhythmias, current angina pectoris requiring a medicinal product, current clinically significant valvular disease, current evidence of transmural infarction on electrocardiogram (ECG), or current poorly controlled hypertension
* Severe dyspnea at rest requiring supplementary oxygen therapy
* History of positivity for hepatitis B surface antigen, hepatitis C virus, or human immunodeficiency virus (HIV)
* Recent infection requiring a course of systemic anti-infectives that were completed ≤ 14 days before enrollment (with the exception of uncomplicated urinary tract infection)
* Woman of childbearing potential who is pregnant or is breast feeding
* Woman of childbearing potential who is not consenting to use highly effective methods of birth control (eg, true abstinence \[periodic abstinence (eg calendar ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\], sterilization, or other non-hormonal forms of contraception) during treatment and for at least 7 months after the last administration of the protocol specified treatment
* Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study
* Other investigational procedures while participating in this study are excluded
* Subject has known sensitivity to any of the products to be administered during the study, including mammalian cell derived drug products, trastuzumab, murine proteins, or to any of the excipients
* Subject previously has enrolled and/or has been randomized in this study
* Subject likely to not be available to complete all protocol required study visits or procedures
* History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the Investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion

Primary outcomes:
measure: Percentage of Participants With a Pathologic Complete Response
timeFrame: 3 to 7 weeks after the last dose of study drug in the neoadjuvant phase
Secondary outcomes:
measure: Percentage of Participants With a Pathologic Complete Response in Breast Tissue Only
timeFrame: 3 to 7 weeks after the last dose of study drug in the neoadjuvant phase
measure: Percentage of Participants With a Pathologic Complete Response in Breast Tissue and Axillary Lymph Nodes and Absence of DCIS
timeFrame: 3 to 7 weeks after the last dose of study drug in the neoadjuvant phase
Other outcomes:
Locations:
city: Brest
country: Belarus
facility: Research Site
city: Grodno
country: Belarus
facility: Research Site
city: Minsk
country: Belarus
facility: Research Site
city: Minsk
country: Belarus
facility: Research Site
city: Salvador
country: Brazil
facility: Research Site
state: Bahia
city: Ijuí
country: Brazil
facility: Research Site
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Research Site
state: RIO Grande DO SUL
city: Jaú
country: Brazil
facility: Research Site
state: SAO Paulo
city: Santo André
country: Brazil
facility: Research Site
state: SAO Paulo
city: São Paulo
country: Brazil
facility: Research Site
state: SAO Paulo
city: Sofia
country: Bulgaria
facility: Research Site
state: Sofiya
city: Veliko Tarnovo
country: Bulgaria
facility: Research Site
state: Veliko Turnovo
city: Pleven
country: Bulgaria
facility: Research Site
city: Varna
country: Bulgaria
facility: Research Site
city: Moncton
country: Canada
facility: Research Site
state: New Brunswick
city: Montréal
country: Canada
facility: Research Site
state: Quebec
city: Temuco
country: Chile
facility: Research Site
state: Cautín
city: Santiago
country: Chile
facility: Research Site
city: Fürstenwalde
country: Germany
facility: Research Site
state: Brandenburg
city: Frankfurt am Main
country: Germany
facility: Research Site
state: Hessen
city: Frankfurt
country: Germany
facility: Research Site
state: Hessen
city: Bonn
country: Germany
facility: Research Site
state: Nordrhein-westfalen
city: Bottrop
country: Germany
facility: Research Site
state: Nordrhein-westfalen
city: Berlin
country: Germany
facility: Research Site
city: Athens
country: Greece
facility: Research Site
state: Attica
city: Athens
country: Greece
facility: Research Site
state: Attica
city: Heraklion
country: Greece
facility: Research Site
state: Crete
city: Thessaloniki
country: Greece
facility: Research Site
state: Nea Efkarpia
city: Debrecen
country: Hungary
facility: Research Site
state: Hajdu-bihar
city: Szolnok
country: Hungary
facility: Research Site
state: Jasz-nagykun-szolnok
city: Nyíregyháza
country: Hungary
facility: Research Site
state: Szabolcs-szatmar-bereg
city: Szekszárd
country: Hungary
facility: Research Site
state: Tolna
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: San Fermo della Battaglia
country: Italy
facility: Research Site
state: Como
city: Bari
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Palermo
country: Italy
facility: Research Site
city: Parma
country: Italy
facility: Research Site
city: Piacenza
country: Italy
facility: Research Site
city: Varese
country: Italy
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
state: Nuevo LEON
city: San Luis Potosí
country: Mexico
facility: Research Site
state: SAN LUIS Potosi
city: Queretaro
country: Mexico
facility: Research Site
city: Toluca, Estado De Mexico
country: Mexico
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
state: Kujawsko-pomorskie
city: Warszawa
country: Poland
facility: Research Site
state: Lubelskie
city: Warszawa
country: Poland
facility: Research Site
state: Mazowieckie
city: Warszawa
country: Poland
facility: Research Site
state: Mazowieckie
city: Gdańsk
country: Poland
facility: Research Site
state: Pomorskie
city: Rybnik
country: Poland
facility: Research Site
state: Slaskie
city: Poznań
country: Poland
facility: Research Site
state: Wielkopolskie
city: Poznań
country: Poland
facility: Research Site
state: Wielkopolskie
city: Cluj-Napoca
country: Romania
facility: Research Site
state: Cluj
city: Ploiesti
country: Romania
facility: Research Site
state: Prahova
city: Timisoara
country: Romania
facility: Research Site
state: Timis
city: Brasov
country: Romania
facility: Research Site
city: Cluj
country: Romania
facility: Research Site
city: Obninsk
country: Russian Federation
facility: Research Site
state: Kaluzhskaya
city: Saransk
country: Russian Federation
facility: Research Site
state: Mordovia
city: Moscow Region
country: Russian Federation
facility: Research Site
state: Moscow
city: Arkhangelsk
country: Russian Federation
facility: Research Site
state: Primorskiy
city: Yaroslavl
country: Russian Federation
facility: Research Site
state: Yaroslavlr
city: Chelaybinsk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Nizhny Novgorod
country: Russian Federation
facility: Research Site
city: Pyatigorsk
country: Russian Federation
facility: Research Site
city: Ryazan
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Sochi
country: Russian Federation
facility: Research Site
city: Belgrade
country: Serbia
facility: Research Site
city: Belgrade
country: Serbia
facility: Research Site
city: Kragujevac
country: Serbia
facility: Research Site
city: Nis
country: Serbia
facility: Research Site
city: Sremska Kamenica
country: Serbia
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
state: Gauteng
city: Durban
country: South Africa
facility: Research Site
state: KwaZulu-Natal
city: Cape Town
country: South Africa
facility: Research Site
state: Western Cape
city: Cape Town
country: South Africa
facility: Research Site
state: Western Cape
city: Sabadell
country: Spain
facility: Research Site
state: Barcelona
city: A Coruña
country: Spain
facility: Research Site
state: LA Coruna
city: Lérida
country: Spain
facility: Research Site
state: Lleida
city: Alcorcón
country: Spain
facility: Research Site
state: Madrid
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
state: Kiev
city: Uzhgorod
country: Ukraine
facility: Research Site
state: Transcarpathia
city: Lutsk
country: Ukraine
facility: Research Site
state: Volyn
city: Chernivtsi
country: Ukraine
facility: Research Site
city: Dnipropetrovsk
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Lviv
country: Ukraine
facility: Research Site
city: Zaporizhzhya
country: Ukraine
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
state: England
city: Peterborough
country: United Kingdom
facility: Research Site
state: England
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Kolberg HC, Colleoni M, Demetriou GS, Santi P, Tesch H, Fujiwara Y, Tomasevic Z, Hanes V. Cardiac Safety of the Trastuzumab Biosimilar ABP 980 in Women with HER2-Positive Early Breast Cancer in the Randomized, Double-Blind, Active-Controlled LILAC Study. Drug Saf. 2020 Mar;43(3):233-242. doi: 10.1007/s40264-019-00886-3.
citation: von Minckwitz G, Colleoni M, Kolberg HC, Morales S, Santi P, Tomasevic Z, Zhang N, Hanes V. Efficacy and safety of ABP 980 compared with reference trastuzumab in women with HER2-positive early breast cancer (LILAC study): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2018 Jul;19(7):987-998. doi: 10.1016/S1470-2045(18)30241-9. Epub 2018 Jun 4.