Study Evaluating Neratinib Versus Lapatinib Plus Capecitabine For ErbB2 Positive Advanced Breast Cancer

A Phase 2 Randomized Open-Label Study of Neratinib Versus Lapatinib Plus Capecitabine For The Treatment Of ErbB-2 Positive Locally Advanced Or Metastatic Breast Cancer

This is a study of an experimental drug (neratinib) versus a combination of drugs (lapatinib and capecitabine) in women who have erbB-2 (HER-2) positive metastatic or locally advanced breast cancer. The goal of this study is to compare the two regimens in shrinking tumors and extending the lives of women with erbB2 (HER2) positive breast cancer. The study will also compare the safety of the two regimens and to compare quality of life of patients taking the two regimens.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Advanced Breast Cancer
• Intervention / Treatment: Drug: Neratinib; Drug: Lapatinib; Drug: Capecitabine

• Study Type: Interventional
• Enrollment (Actual): 233
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • West Perth, Australia, 6000
    • Mount Hospital
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Mater Private Centre for HOCA
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Medical Oncology Royal Adelaide Hospital
  • Victoria
    • Footscray, Victoria, Australia, 3011
      • Western Hospital
• Austria
  • Wien, Austria, A-1090
    • AKH Wien Universitaetsklinik fuer Innere Medizin I Klinische Abteilung für Onkologie
• Belgium
  • Brussels, Belgium, 1000
    • Institut Jules Bordet Unite du Chimiotherapie
• Bulgaria
  • Sofia, Bulgaria, 1233
    • District Dispensary for Oncology Diseases Internal Unit- Sofia EOOD, Dept. of Chemotherapy
  • Sofia, Bulgaria, 1527
    • UMHAT Tzaritza Yoanna
  • Varna, Bulgaria, 9000
    • Interdistrict Dispensary for Oncology Diseases -Internal Unit- Department Oncotherapy and Palliative Care
• Canada
  • Quebec, Canada, G1S 4L8
    • Centre Hospitalier Affilie Universitaire de Quebec Hopital du St-Sacrement
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BC Cancer Agency - Vancouver Centre
• Croatia
  • Varazdin, Croatia, 42000
    • General Hospital Varazdin
  • Zagreb, Croatia, 10000
    • University Hospital Center Zagreb
  • Zagreb, Croatia, 10000
    • University Hospital Sestre Milosrdnice
• Czechia
  • Olomouc, Czechia, 775 20
    • Fakultni nemocnice Olomouc Klinika onkologie
• France
  • Lille, France, 59020
    • Centre Oscar Lambret Département de Sénologie
  • Pierre Benite, France, 69340
    • Centre Hospitalier Lyon Sud
  • Poitiers, France, 86021
    • CHU de Poitiers Service d'oncologie medicale
  • Villejuif, France, 94805
    • Institut Gustave ROUSSY Service de Pathologie Mammaire
• Germany
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg-Eppendorf Klinik und Poliklinik fuer Gynaekologie
  • Heidelberg, Germany, 69120
    • Nationales Centrum fuer Tumorerkrankungen Sektion Gynaekologische Onkologie
• Greece
  • Thessaloníki, Greece, 54007
    • Theagenio Anticancer Hospital of Thessaloniki
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Department of Clinical Oncology, Tuen Mun Hospital
  • Hong Kong, Hong Kong
    • UNIMED Medical Institute, Comprehensive Centre for Breast Diseases
• Hungary
  • Budapest, Hungary, 1122
    • Országos Onkológiai Intézet "B" Belgyogyaszati osztaly
  • Budapest, Hungary, 1032
    • Fovarosi Onkormanyzat Szent Janos Korhaza es Eszak-budai Egyesitett Korhazai, Onkologia
  • Kecskemet, Hungary, 6000
    • Bacs-Kiskun Megyei Korhaz Onkoradiologiai Kozpont
  • Nyiregyhaza, Hungary, 4400
    • Josa Andras Oktatokorhaz / Onkoradiologiai Osztaly
  • Szeged, Hungary, 6720
    • Szegedi Tudomanyegyetem Onkoterapias Klinika
  • Veszprem, Hungary, 8200
    • Hospital of County Veszprem
• Italy
  • Prato, Italy, 59100
    • Ospedale Misericordia e Dolce c/o UO Oncologia Medica
  • Roma, Italy, 00144
    • Istituto Regina Elena, Struttura Complessa Oncologia Medica A
• Japan
  • Aichi, Japan
    • Aichi Cancer Center
  • Chiba, Japan
    • National Cancer Center Hospital East
  • Chiba, Japan
    • Chiba Cancer Center
  • Fukuoka, Japan
    • National Hospital Organization Kyushu Cancer Center
  • Hiroshima, Japan
    • Hiroshima City Hospital
  • Hyogo, Japan
    • Hyogo Cancer Center
  • Kagoshima, Japan
    • Hakuaikai Medical Corporation Sagara Hospital
  • Kanagawa, Japan
    • Tokai University Hospital
  • Kumamoto, Japan
    • Kumamoto Municipal Hospital
  • Kyoto, Japan
    • Kyoto University Hospital
  • Niigata, Japan
    • Niigata Cancer Center Hospital
  • Osaka, Japan
    • National Hospital Organization Osaka National Hospital
  • Saitama, Japan
    • Saitama Cancer Center
  • Shizuoka, Japan
    • Shizuoka Cancer Center
  • Tochigi, Japan
    • Jichi Medical University Hospital
  • Tokyo, Japan
    • St. Luke's International Hospital
  • Tokyo, Japan
    • The Cancer Institute Hospital of Japanese Foundation for Cancer Research Department of Medical Oncology
  • Tokyo, Japan
    • Tokyo Metropolitan Cancer&Infectious disease Ctr Komagome Hp
  • Hokkaido
    • Sapporo, Hokkaido, Japan
      • National Hospital Organization Hokkaido Cancer Center
  • Tokyo
    • Tsukiji, Tokyo, Japan
      • National Cancer Center Hospital
• Jordan
  • Amman, Jordan, 11941
    • King Hussein Cancer Centre
• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Seoul, Korea, Republic of, 120-752
    • Yonsei University Health System - Severance Hospital
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769
      • National Cancer Center
  • Korea
    • Seoul, Korea, Korea, Republic of, 135-710
      • Samsung Medical Center
• Mexico
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64000
      • Oca Hospital / Monterrey International Research Center
• Poland
  • Bialystok, Poland, 15-027
    • Bialostockie Centrum Onkologii im. M. Sklodowskiej-Curie w Bialymstoku Specjalistyczny Szpital Onkologiczn
  • Gdansk, Poland, 80952
    • Uniwersyteckie Centrum Kliniczne w Gdansku Klinika Onkologii i Radioterapii
  • Krakow, Poland, 31-531
    • Szpital Uniwersytecki w Krakowie Oddzial KIiniczny Kliniki Onkologii
  • Lublin, Poland, 20-090
    • Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli
• Puerto Rico
  • San Juan, Puerto Rico, 00910
    • Metropolitan Oncology Center
• Romania
  • Bucuresti, Romania, 050098
    • Spitalul Universitar de Urgenţă
  • Bucuresti, Romania, 022328
    • Institutul Oncologic "Prof. Dr. Alex. Trestioreanu"
  • Iasi, Romania, 700106
    • Centrul de Oncologie Medicala
  • Sibiu, Romania, 550245
    • Spitalul clinic judetean
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Russian Oncology Research Centre of RAMS
  • Perm, Russian Federation, 614066
    • GUZ Perm Regional Oncology Dispensary
  • Ryazan, Russian Federation, 390011
    • Ryazan State Medical University I.P.Pavlov of Federal Agency in Healthcare and Social Development
  • Saint Petersburg, Russian Federation, 191104
    • SIH Leningrad Regional Oncology Dispensary
  • Saint Petersburg, Russian Federation, 197022
    • GUZ City Clinical Oncology Dispensary
  • Saint Petersburg, Russian Federation, 197022
    • St. Petersburg State Medical University I.P.Pavlov of Roszdrav
  • Sochi, Russian Federation, 354057
    • SIH Oncology Dispensary # 2 Of Department of Public Health
  • Ufa, Russian Federation, 450054
    • Republican Clinical Oncology Dispensary of Ministry of Healthcare of Bashkortostan Republic
  • Saint Petersburg
    • Pesochny, Saint Petersburg, Russian Federation, 197758
      • Scientific Research Institute of Oncology N.N. Petrov
• Serbia
  • Belgrade, Serbia, 11000
    • Institute of Oncology and Radiology of Serbia
  • Belgrade, Serbia, 11000
    • Klinicko Bolnicki Centar (KBC) Bezanijska Kosa (Medical Centre ''Bezanijska Kosa'' (MCBK))
• Singapore
  • Singapore, Singapore, 308433
    • Johns Hopkins Singapore International Medical Centre
• Slovenia
  • Ljubljana, Slovenia, 1000
    • Institute for Oncology Department for Medical Oncology
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2196
      • The Medical Oncology Centre of Rosebank
    • Lynnwood, Gauteng, South Africa, 0081
      • Eastleigh Breast Care Centre
  • KwaZulu Natal
    • Durban, KwaZulu Natal, South Africa, 4001
      • Hopelands Oncology Centre
  • Western Cape Province
    • Kraaifontein, Western Cape Province, South Africa
      • GVI Oncology Trial Unit Room 110 Panorama Medical Centre
• Spain
  • A Coruña, Spain, 15006
    • Complejo Hospitalario U. de A Coruña Hospital Teresa Herrera Servicio de Oncologia
  • Alicante, Spain, 03010
    • Hospital General Universitario de Alicante Servicio de Oncologia
  • Caceres, Spain, 10003
    • Hospital San Pedro de Alcantara Servicio de Oncologia
  • Cordoba, Spain, 14004
    • Hospital Provincial (Reina Sofia) Servicio de Oncologia
  • Gerona, Spain, 17007
    • Hospital Universitario Dr. Josep Trueta Servicio de Oncologia
  • Jaen, Spain, 23007
    • Centro Hospitalario de Jaen Servicio de Oncologia
  • Madrid, Spain, 28007
    • Hospital Gregorio Marañon Servicio de Oncologia
  • Madrid, Spain, 28033
    • Centro Oncologico M.D. Anderson Internacional
  • Valencia, Spain, 46009
    • Instituto Valenciano de Oncologia Servicio de Oncologia
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia Servicio de Hematologia y Oncologia
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet Servicio de Oncología
  • Asturias
    • Oviedo, Asturias, Spain, 33006
      • Hospital Central de Asturias Servicio de Oncologia, Planta Baja Oeste, Edificio Principal
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Germans Trias i Pujol Servicio de Oncologia
    • Sabadell, Barcelona, Spain, 08208
      • Corporacio Sanitaria Parc Tauli Servicio de Oncologia
    • Terrassa, Barcelona, Spain, 08221
      • Hospital Mutua de Terrassa Servicio de Oncologia
• Switzerland
  • Lausanne, Switzerland, 1011
    • University of Lausanne Hospitals CHUV
  • Winterthur, Switzerland, 8401
    • Kantonsspital Winterthur Medizinische Onkologie
  • Zuerich, Switzerland, CH-8091
    • Abteilung fuer Onkologie Departement für Innere
• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
• Thailand
  • Bangkok
    • Bangkok-noi, Bangkok, Thailand, 10700
      • Division of Medical Oncology, Department of Medicine
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden NHS Foundation Trust & Institute of Cancer Research
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS Foundation Trust & Institute of Cancer Research
  • Essex
    • Chelmsford, Essex, United Kingdom, CM1 7ET
      • Broomfield Hospital
• United States
  • Arizona
    • Tucson, Arizona, United States, 85704-7891
      • Arizona Oncology Associates HOPE
  • California
    • Murrieta, California, United States, 92562
      • Southwest Cancer Care
    • Orange, California, United States, 92868-3298
      • UC Irvine Medical Center
    • Palm Springs, California, United States, 92262
      • Aptium Oncology/Comprehensive Cancer Center at Desert Regional Medical Center
    • Santa Rosa, California, United States, 95403
      • Redwood Regional Medical Group, Inc.
  • Colorado
    • Denver, Colorado, United States, 80220
      • Rocky Mountain Cancer Center
  • Connecticut
    • Stamford, Connecticut, United States, 06902
      • Hematology Oncology Associates, P.C.
  • Florida
    • Boynton Beach, Florida, United States, 33435
      • Palm Beach Institute of Hematology & Oncology
    • Gainesville, Florida, United States, 32605
      • Robert R. Carroll, MD, PA
    • Jacksonville, Florida, United States, 32209
      • University of Florida
    • Loxahatchee Groves, Florida, United States, 33470
      • Hematology Oncology Associates
    • Miami, Florida, United States, 33133
      • Mercy Research Institute
    • Orlando, Florida, United States, 32806
      • Cancer Centers of Florida
    • Port Saint Lucie, Florida, United States, 34952
      • Hematology Oncology Associates of the Treasure Coast
  • Illinois
    • Decatur, Illinois, United States, 62526
      • Cancer Care Specialists of Central Illinois
    • Park Ridge, Illinois, United States, 60068
      • Oncology Specialists, SC
    • Zion, Illinois, United States, 60099
      • Midwestern Regional Medical Center
  • Indiana
    • Fishers, Indiana, United States, 46037
      • Central Indiana Cancer Centers
    • Indianapolis, Indiana, United States, 46260-2082
      • Hematology Oncology of Indiana
    • New Albany, Indiana, United States, 47150
      • Floyd Memorial Cancer Center of Indiana
  • Kentucky
    • Ashland, Kentucky, United States, 41101
      • Ashland-Bellefonte Cancer Center
    • Louisville, Kentucky, United States, 40245
      • Owsley Brown Frazier Cancer Center (OBFCC)
    • Paducah, Kentucky, United States, 42001
      • Purchase Cancer Group
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Missouri Cancer Associates
    • Jefferson City, Missouri, United States, 65109
      • Capitol Comprehensive Cancer Care Clinic
  • New York
    • Lake Success, New York, United States, 11042
      • Arena Oncology Associates, PC
    • New York, New York, United States, 10065
      • Weill Cornell Medical College New York-Presbyterian Hospital Weill, Cornell Breast Center
    • Troy, New York, United States, 12180
      • New York Oncology Hematolgy, PC
  • Ohio
    • Cincinnati, Ohio, United States, 45247
      • Oncology Partners Network
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center, Cancer Care Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center Dept. of Hematology Oncology
  • Oregon
    • Portland, Oregon, United States, 97213
      • Northwest Cancer Specialists, PC
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17605
      • Lancaster Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital Allegheny Cancer Center
  • Tennessee
    • Cookeville, Tennessee, United States, 38501
      • Cookeville Regional Medical Center
    • Knoxville, Tennessee, United States, 37909
      • Center for Biomedical Research
    • Knoxville, Tennessee, United States, 37916
      • Thompson Cancer Survival Center Thompson Oncology Group
    • Memphis, Tennessee, United States, 38104
      • University of Tennessee Cancer Institute
  • Texas
    • Austin, Texas, United States, 78731-4214
      • Texas Oncology, P.A.
    • El Paso, Texas, United States, 79902
      • El Paso Cancer Treatment Center - West
    • Fort Worth, Texas, United States, 76104
      • The Center for Cancer and Blood Disorders
    • Richardson, Texas, United States, 75080
      • HOPE Oncology
    • San Antonio, Texas, United States, 78229
      • Cancer Care Network of South Texas-HOAST
    • Tyler, Texas, United States, 75701-2043
      • East Texas Medical Center Cancer Institute, Tyler Hematology Oncology

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:

• Stage IIIB, IIIC, or IV erbB2 (HER2) positive breast cancer
• Prior use of Herceptin (trastuzumab), and a taxane
• Adequate cardiac and renal function

Exclusion Criteria:

• More than 2 prior Herceptin (trastuzumab) regimens or prior use of Xeloda (capecitabine) and / or Tykerb (lapatinib) [Tyverb]
• Bone as the only site of disease
• Active central nervous system metastases (subjects should be stable and off anticonvulsants and steroids)
• Significant gastrointestinal disorder with diarrhea as major symptom

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Neratinib	Drug: Neratinib; Tablets 240 mg orally once per day until disease progression or unacceptable toxicity; Other Names: HKI-272
ACTIVE_COMPARATOR: Lapatinib plus Capecitabine	Drug: Lapatinib; Tablets 1250 mg orally once per day until disease progression or unacceptable toxicity.; Other Names: Tykerb, Tyverb; Drug: Capecitabine; Tablets 2000 mg/m² given orally in two evenly divided daily doses for first 14 days of each 21 day cycle. Given until disease progression or unacceptable toxicity.; Other Names: Xeloda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Progression Free Survival, Measured in Months, for Subjects Randomized. Investigator assessment. The time interval from the date of randomization until the earliest date of progression per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) or death due to any cause. For subjects without death or progression, censorship was at the last valid tumor assessment.	From randomization date to progression or death, assessed up to 69 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall Survival (OS) was defined as the time from randomization to death due to any cause. Subjects last known to be alive were censored at the last date of last contact or the data cutoff employed for the analysis, whichever was earlier.	From randomization date to death, assessed up to 69 months
Objective Response Rate (ORR).	Objective Response Rate, investigator assessment. The ORR was defined as the percentage of participants demonstrating a confirmed objective response, either Complete Response (CR) or Partial Response (PR) during the study per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.	From randomization date to progression or last tumor assessment, assessed up to 69 months
Clinical Benefit Rate	Clinical benefit rate (CR, PR, or SD = 24 weeks) for women For ErbB2 Positive Advanced Breast Cancer. Clinical benefit rate was the percentage of subjects who achieved overall tumor response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Clinical Benefit (CB) = CR + PR + SD >= 24 weeks.	From randomization date to progression or last tumor assessment, assessed up to 69 months
Duration of Response	Duration of response was measured from the time at which response criteria were met for complete response (CR) or partial response (PR) (whichever status was recorded first) until the first date of recurrence or progressive disease (PD) or death. For subjects without death or progression, censorship was at the last valid tumor assessment per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.	From start date of response to first PD, assessed up to 69 months after the first subject was randomized.
Frequency of CNS Metastases (Frequency)	The percent of patients with symptomatic or progressive CNS lesions was the proportion of subjects who had PD considering CNS lesions only, according to RECIST criteria.	From randomization date to first CNS symptom or lesions
Time to CNS Metastases	Time to symptomatic or progressive Central nervous system (CNS) lesions. Time to symptomatic or progressive CNS lesions was the time from the date of randomization until the date of progressive disease (PD) considering CNS lesions only (ie, appearance of newly diagnosed CNS lesions or progressive CNS lesions).	From randomization date to first CNS symptom or lesions

Collaborators and Investigators

• Sponsor: Puma Biotechnology, Inc.

Publications and helpful links

General Publications

• Martin M, Bonneterre J, Geyer CE Jr, Ito Y, Ro J, Lang I, Kim SB, Germa C, Vermette J, Wang K, Wang K, Awada A. A phase two randomised trial of neratinib monotherapy versus lapatinib plus capecitabine combination therapy in patients with HER2+ advanced breast cancer. Eur J Cancer. 2013 Dec;49(18):3763-72. doi: 10.1016/j.ejca.2013.07.142. Epub 2013 Aug 15.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 4, 2009
• Primary Completion (ACTUAL): March 1, 2011
• Study Completion (ACTUAL): June 3, 2018

Study Registration Dates

• First Submitted: October 21, 2008
• First Submitted That Met QC Criteria: October 21, 2008
• First Posted (ESTIMATE): October 22, 2008

Study Record Updates

• Last Update Posted (ACTUAL): August 9, 2018
• Last Update Submitted That Met QC Criteria: July 11, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: capecitabine; HER2; metastatic; lapatinib; HKI-272; Nerlynx; PB-272; ErbB2; neratinib
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protein Kinase Inhibitors; Capecitabine; Lapatinib
• Other Study ID Numbers: 3144A2-3003 / B1891003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No