Efficacy and Safety Study of ABP 980 Compared With Trastuzumab in Women With HER2-positive Early Breast Cancer

NCT ID: NCT01901146

Last Updated: 2019-08-07

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

725 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-04-29

Study Completion Date

2017-01-27

Brief Summary

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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.

Detailed Description

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Conditions

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Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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ABP 980

Participants received ABP 980 at an initial dose of 8 mg/kg by intravenous (IV) infusion, then 6 mg/kg IV infusion every 3 weeks (Q3W) for 3 additional cycles plus 175 mg/m² paclitaxel Q3W for 4 cycles during the neoadjuvant phase.

Surgery (lumpectomy or mastectomy with sentinel lymph node dissection or axillary lymph node dissection) was completed 3 to 7 weeks after the last dose of study drug in the neoadjuvant phase.

After surgery (adjuvant phase) participants continued receiving 6 mg/kg ABP 980 IV Q3W for up to 1 year from the first day of study drug administration in the neoadjuvant phase.

Group Type EXPERIMENTAL

ABP 980

Intervention Type DRUG

ABP 980 was administered at an initial dose of 8 mg/kg over a 90-minute intravenous (IV) infusion, then 6 mg/kg IV infusion Q3W for all subsequent cycles.

Paclitaxel

Intervention Type DRUG

Paclitaxel, 175 mg/m² Q3W for 4 cycles (or 80 mg/m² QW for 12 cycles, if local standard of care).

Lumpectomy or Mastectomy with Sentinel Node or Axillary Node Dissection

Intervention Type PROCEDURE

Trastuzumab

Participants received trastuzumab at an initial dose of 8 mg/kg IV infusion, then 6 mg/kg IV infusion Q3W for 3 additional cycles plus 175 mg/m² paclitaxel Q3W for 4 cycles during the neoadjuvant phase.

Surgery (lumpectomy or mastectomy with sentinel lymph node dissection or axillary lymph node dissection) was completed 3 to 7 weeks after the last dose of study drug in the neoadjuvant phase.

After surgery (adjuvant phase) participants were re-randomized to either continue receiving 6 mg/kg trastuzumab IV Q3W or transition to 6 mg/kg ABP 980 IV Q3W for up to 1 year from the first day of study drug administration in the neoadjuvant phase.

Group Type ACTIVE_COMPARATOR

Trastuzumab

Intervention Type DRUG

Trastuzumab was administered at an initial dose of 8 mg/kg over a 90-minute IV infusion, then 6 mg/kg IV infusion Q3W for all subsequent cycles.

Paclitaxel

Intervention Type DRUG

Paclitaxel, 175 mg/m² Q3W for 4 cycles (or 80 mg/m² QW for 12 cycles, if local standard of care).

Lumpectomy or Mastectomy with Sentinel Node or Axillary Node Dissection

Intervention Type PROCEDURE

Interventions

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ABP 980

ABP 980 was administered at an initial dose of 8 mg/kg over a 90-minute intravenous (IV) infusion, then 6 mg/kg IV infusion Q3W for all subsequent cycles.

Intervention Type DRUG

Trastuzumab

Trastuzumab was administered at an initial dose of 8 mg/kg over a 90-minute IV infusion, then 6 mg/kg IV infusion Q3W for all subsequent cycles.

Intervention Type DRUG

Paclitaxel

Paclitaxel, 175 mg/m² Q3W for 4 cycles (or 80 mg/m² QW for 12 cycles, if local standard of care).

Intervention Type DRUG

Lumpectomy or Mastectomy with Sentinel Node or Axillary Node Dissection

Intervention Type PROCEDURE

Other Intervention Names

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Herceptin®

Eligibility Criteria

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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


* 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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Actavis Inc.

INDUSTRY

Sponsor Role collaborator

Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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Brest, , Belarus

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Grodno, , Belarus

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Minsk, , Belarus

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Minsk, , Belarus

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Salvador, Estado de Bahia, Brazil

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Ijuí, Rio Grande do Sul, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Jaú, São Paulo, Brazil

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Santo André, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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Sofia, Sofia, Bulgaria

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Veliko Tarnovo, Veliko Tarnovo, Bulgaria

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Pleven, , Bulgaria

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Varna, , Bulgaria

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Moncton, New Brunswick, Canada

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Montreal, Quebec, Canada

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Temuco, Cautín, Chile

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Santiago, , Chile

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Fürstenwalde, Brandenburg, Germany

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Frankfurt am Main, Hesse, Germany

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Frankfurt am Main, Hesse, Germany

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Bonn, North Rhine-Westphalia, Germany

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Bottrop, North Rhine-Westphalia, Germany

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Berlin, , Germany

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Athens, Attica, Greece

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Athens, Attica, Greece

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Heraklion, Crete, Greece

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Thessaloniki, Nea Efkarpia, Greece

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Debrecen, Hajdú-Bihar, Hungary

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Szolnok, Jász-Nagykun-Szolnok, Hungary

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Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary

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Szekszárd, Tolna County, Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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San Fermo della Battaglia, COMO, Italy

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Bari, , Italy

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Milan, , Italy

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Palermo, , Italy

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Parma, , Italy

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Piacenza, , Italy

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Varese, , Italy

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Toluca, Estado de Mexico, Mexico, Mexico

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Monterrey, Nuevo León, Mexico

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San Luis Potosí City, San Luis Potosí, Mexico

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Querétaro, , Mexico

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Poznan, Greater Poland Voivodeship, Poland

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Poznan, Greater Poland Voivodeship, Poland

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Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

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Warszawa, Lublin Voivodeship, Poland

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Warsaw, Masovian Voivodeship, Poland

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Warsaw, Masovian Voivodeship, Poland

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Gdansk, Pomeranian Voivodeship, Poland

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Rybnik, Silesian Voivodeship, Poland

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Cluj-Napoca, Cluj, Romania

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Ploieşti, Prahova, Romania

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Timișoara, Timiș County, Romania

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Brasov, , Romania

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Cluj-Napoca, , Romania

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Obninsk, Kaluzhskaya, Russia

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Moscow Region, Moscow, Russia

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Arkhangelsk, Primorskiy (Maritime) Kray, Russia

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Saransk, Respublika Mordoviya, Russia

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Yaroslavl, Yaroslavlr, Russia

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Chelaybinsk, , Russia

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Moscow, , Russia

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Nizhny Novgorod, , Russia

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Pyatigorsk, , Russia

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Ryazan, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Sochi, , Russia

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Belgrade, , Serbia

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Belgrade, , Serbia

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Kamenitz, , Serbia

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Kragujevac, , Serbia

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Niš, , Serbia

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Johannesburg, Gauteng, South Africa

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Durban, KwaZulu-Natal, South Africa

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Cape Town, Western Cape, South Africa

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Cape Town, Western Cape, South Africa

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Sabadell, Barcelona, Spain

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A Coruña, LA Coruna, Spain

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Lleida, Lleida, Spain

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Alcorcón, Madrid, Spain

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Barcelona, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Kyiv, Kyiv City, Ukraine

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Lutsk, Volyn Oblast, Ukraine

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Uzhhorod, Zakarpattia Oblast, Ukraine

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Chernivtsi, , Ukraine

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Dnipropetrovsk, , Ukraine

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Kharkiv, , Ukraine

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Lviv, , Ukraine

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Zaporizhzhya, , Ukraine

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Nottingham, England, United Kingdom

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Peterborough, England, United Kingdom

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Countries

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Belarus Brazil Bulgaria Canada Chile Germany Greece Hungary Italy Mexico Poland Romania Russia Serbia South Africa Spain Ukraine United Kingdom

References

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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.

Reference Type DERIVED
PMID: 31927716 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29880292 (View on PubMed)

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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2012-004319-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20120283

Identifier Type: -

Identifier Source: org_study_id

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