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

NCT00777101 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 3144A2-3003 / B1891003
• Study Type: interventional
• Target: 233
• Locations: 30 countries
• Sites: 148

Brief Summary

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.

Conditions

Advanced Breast Cancer; Breast Cancer

Keywords

HER2; ErbB2; metastatic; neratinib; lapatinib; capecitabine; HKI-272; Nerlynx; PB-272

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Overall Survival (OS)

  From randomization date to death, assessed up to 69 months

• Objective Response Rate (ORR).

  From randomization date to progression or last tumor assessment, assessed up to 69 months

• Clinical Benefit Rate

  From randomization date to progression or last tumor assessment, assessed up to 69 months

• Duration of Response

  From start date of response to first PD, assessed up to 69 months after the first subject was randomized.

• Frequency of CNS Metastases (Frequency)

  From randomization date to first CNS symptom or lesions

Study Arms (2)

Neratinib

EXPERIMENTAL

Drug: Neratinib

Lapatinib plus Capecitabine

ACTIVE COMPARATOR

Drug: Lapatinib; Drug: Capecitabine

Interventions

Neratinib DRUG

Tablets 240 mg orally once per day until disease progression or unacceptable toxicity

Also known as: HKI-272

Neratinib

Lapatinib DRUG

Tablets 1250 mg orally once per day until disease progression or unacceptable toxicity.

Also known as: Tykerb, Tyverb

Lapatinib plus Capecitabine

Capecitabine DRUG

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.

Also known as: Xeloda

Lapatinib plus Capecitabine

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Puma Biotechnology, Inc.: lead

Study Sites (152)

Arizona Oncology Associates HOPE

Tucson, Arizona, 85704-7891, United States

Location

Southwest Cancer Care

Murrieta, California, 92562, United States

Location

UC Irvine Medical Center

Orange, California, 92868-3298, United States

Location

Aptium Oncology/Comprehensive Cancer Center at Desert Regional Medical Center

Palm Springs, California, 92262, United States

Location

Redwood Regional Medical Group, Inc.

Santa Rosa, California, 95403, United States

Location

Rocky Mountain Cancer Center

Denver, Colorado, 80220, United States

Location

Hematology Oncology Associates, P.C.

Stamford, Connecticut, 06902, United States

Location

Palm Beach Institute of Hematology & Oncology

Boynton Beach, Florida, 33435, United States

Location

Robert R. Carroll, MD, PA

Gainesville, Florida, 32605, United States

Location

University of Florida

Jacksonville, Florida, 32209, United States

Location

Hematology Oncology Associates

Loxahatchee Groves, Florida, 33470, United States

Location

Mercy Research Institute

Miami, Florida, 33133, United States

Location

Cancer Centers of Florida

Orlando, Florida, 32806, United States

Location

Hematology Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida, 34952, United States

Location

Cancer Care Specialists Of Central Illinois

Decatur, Illinois, 62526, United States

Location

Oncology Specialists, SC

Park Ridge, Illinois, 60068, United States

Location

Midwestern Regional Medical Center

Zion, Illinois, 60099, United States

Location

Central Indiana Cancer Centers

Fishers, Indiana, 46037, United States

Location

Hematology Oncology of Indiana

Indianapolis, Indiana, 46260-2082, United States

Location

Floyd Memorial Cancer Center of Indiana

New Albany, Indiana, 47150, United States

Location

Ashland-Bellefonte Cancer Center

Ashland, Kentucky, 41101, United States

Location

Owsley Brown Frazier Cancer Center (OBFCC)

Louisville, Kentucky, 40245, United States

Location

Purchase Cancer Group

Paducah, Kentucky, 42001, United States

Location

Missouri Cancer Associates

Columbia, Missouri, 65201, United States

Location

Capitol Comprehensive Cancer Care Clinic

Jefferson City, Missouri, 65109, United States

Location

Arena Oncology Associates, PC

Lake Success, New York, 11042, United States

Location

Weill Cornell Medical College New York-Presbyterian Hospital Weill, Cornell Breast Center

New York, New York, 10065, United States

Location

New York Oncology Hematolgy, PC

Troy, New York, 12180, United States

Location

Oncology Partners Network

Cincinnati, Ohio, 45247, United States

Location

MetroHealth Medical Center, Cancer Care Center

Cleveland, Ohio, 44109, United States

Location

University of Oklahoma Health Sciences Center Dept. of Hematology Oncology

Oklahoma City, Oklahoma, 73104, United States

Location

Northwest Cancer Specialists, PC

Portland, Oregon, 97213, United States

Location

Lancaster Cancer Center

Lancaster, Pennsylvania, 17605, United States

Location

Allegheny General Hospital Allegheny Cancer Center

Pittsburgh, Pennsylvania, 15212, United States

Location

Cookeville Regional Medical Center

Cookeville, Tennessee, 38501, United States

Location

Center for Biomedical Research

Knoxville, Tennessee, 37909, United States

Location

Thompson Cancer Survival Center Thompson Oncology Group

Knoxville, Tennessee, 37916, United States

Location

University of Tennessee Cancer Institute

Memphis, Tennessee, 38104, United States

Location

Texas Oncology, P.A.

Austin, Texas, 78731-4214, United States

Location

El Paso Cancer Treatment Center - West

El Paso, Texas, 79902, United States

Location

The Center for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

Location

HOPE Oncology

Richardson, Texas, 75080, United States

Location

Cancer Care Network of South Texas-HOAST

San Antonio, Texas, 78229, United States

Location

East Texas Medical Center Cancer Institute, Tyler Hematology Oncology

Tyler, Texas, 75701-2043, United States

Location

Mater Private Centre for HOCA

South Brisbane, Queensland, 4101, Australia

Location

Medical Oncology Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Western Hospital

Footscray, Victoria, 3011, Australia

Location

Mount Hospital

West Perth, 6000, Australia

Location

AKH Wien Universitaetsklinik fuer Innere Medizin I Klinische Abteilung für Onkologie

Vienna, A-1090, Austria

Location

Institut Jules Bordet Unite du Chimiotherapie

Brussels, 1000, Belgium

Location

District Dispensary for Oncology Diseases Internal Unit- Sofia EOOD, Dept. of Chemotherapy

Sofia, 1233, Bulgaria

Location

UMHAT Tzaritza Yoanna

Sofia, 1527, Bulgaria

Location

Interdistrict Dispensary for Oncology Diseases -Internal Unit- Department Oncotherapy and Palliative Care

Varna, 9000, Bulgaria

Location

BC Cancer Agency - Vancouver Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Centre Hospitalier Affilie Universitaire de Quebec Hopital du St-Sacrement

Québec, Quebec, G1S 4L8, Canada

Location

General Hospital Varazdin

Varaždin, 42000, Croatia

Location

University Hospital Center Zagreb

Zagreb, 10000, Croatia

Location

University Hospital Sestre Milosrdnice

Zagreb, 10000, Croatia

Location

Fakultni nemocnice Olomouc Klinika onkologie

Olomouc, 775 20, Czechia

Location

Centre Oscar Lambret Departement de senologie

Lille, 59020, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69340, France

Location

CHU de Poitiers Service d'oncologie medicale

Poitiers, 86021, France

Location

Institut Gustave ROUSSY Service de Pathologie mammaire

Villejuif, 94805, France

Location

Universitaetsklinikum Hamburg-Eppendorf Klinik und Poliklinik fuer Gynaekologie

Hamburg, 20246, Germany

Location

Nationales Centrum fuer Tumorerkrankungen Sektion Gynaekologische Onkologie

Heidelberg, 69120, Germany

Location

Theagenio Anticancer Hospital of Thessaloniki

Thessaloniki, 54007, Greece

Location

Department of Clinical Oncology, Tuen Mun Hospital

Hong Kong, Hong Kong

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

UNIMED Medical Institute, Comprehensive Centre for Breast Diseases

Hong Kong, Hong Kong

Location

Fovarosi Onkormanyzat Szent Janos Korhaza es Eszak-budai Egyesitett Korhazai, Onkologia

Budapest, 1032, Hungary

Location

Orszagos Onkologiai Intezet "B" Belgyogyaszati osztaly

Budapest, 1122, Hungary

Location

Bacs-Kiskun Megyei Korhaz Onkoradiologiai Kozpont

Kecskemét, 6000, Hungary

Location

Josa Andras Oktatokorhaz / Onkoradiologiai Osztaly

Nyíregyháza, 4400, Hungary

Location

Szegedi Tudomanyegyetem Onkoterapias Klinika

Szeged, 6720, Hungary

Location

Hospital of County Veszprem

Veszprém, 8200, Hungary

Location

Ospedale Misericordia e Dolce c/o UO Oncologia Medica

Prato, 59100, Italy

Location

Istituto Regina Elena, Struttura Complessa Oncologia Medica A

Roma, 00144, Italy

Location

National Hospital Organization Hokkaido Cancer Center

Sapporo, Hokkaido, Japan

Location

National Cancer Center Hospital

Tsukiji, Tokyo, Japan

Location

Aichi Cancer Center

Aichi, Japan

Location

Chiba Cancer Center

Chiba, Japan

Location

National Cancer Center Hospital East

Chiba, Japan

Location

National Hospital Organization Kyushu Cancer Center

Fukuoka, Japan

Location

Hiroshima City Hospital

Hiroshima, Japan

Location

Hyogo Cancer Center

Hyōgo, Japan

Location

Hakuaikai Medical Corporation Sagara Hospital

Kagoshima, Japan

Location

Tokai University Hospital

Kanagawa, Japan

Location

Kumamoto Municipal Hospital

Kumamoto, Japan

Location

Kyoto University Hospital

Kyoto, Japan

Location

Niigata Cancer Center Hospital

Niigata, Japan

Location

National Hospital Organization Osaka National Hospital

Osaka, Japan

Location

Saitama Cancer Center

Saitama, Japan

Location

Shizuoka Cancer Center

Shizuoka, Japan

Location

Jichi Medical University Hospital

Tochigi, Japan

Location

St. Luke's International Hospital

Tokyo, Japan

Location

The Cancer Institute Hospital of Japanese Foundation for Cancer Research Department of Medical Oncology

Tokyo, Japan

Location

Tokyo Metropolitan Cancer&Infectious disease Ctr Komagome Hp

Tokyo, Japan

Location

King Hussein Cancer Centre

Amman, 11941, Jordan

Location

Oca Hospital / Monterrey International Research Center

Monterrey, Nuevo León, 64000, Mexico

Location

Bialostockie Centrum Onkologii im. M. Sklodowskiej-Curie w Bialymstoku Specjalistyczny Szpital Onkologiczn

Bialystok, 15-027, Poland

Location

Uniwersyteckie Centrum Kliniczne w Gdansku Klinika Onkologii i Radioterapii

Gdansk, 80952, Poland

Location

Szpital Uniwersytecki w Krakowie Oddzial KIiniczny Kliniki Onkologii

Krakow, 31-531, Poland

Location

Centrum Onkologii Ziemi Lubelskiej im. SW. Jana z Dukli

Lublin, 20-090, Poland

Location

Metropolitan Oncology Center

San Juan, PR, 00910, Puerto Rico

Location

Institutul Oncologic "Prof. Dr. Alex. Trestioreanu"

Bucharest, 022328, Romania

Location

Spitalul Universitar de Urgenta

Bucharest, 050098, Romania

Location

Centrul de Oncologie Medicala

Iași, 700106, Romania

Location

Spitalul Clinic Judetean

Sibiu, 550245, Romania

Location

Scientific Research Institute of Oncology N.N. Petrov

Pesochny, Sankt-Peterburg, 197758, Russia

Location

Russian Oncology Research Centre of RAMS

Moscow, 115478, Russia

Location

GUZ Perm Regional Oncology Dispensary

Perm, 614066, Russia

Location

Ryazan State Medical University I.P.Pavlov of Federal Agency in Healthcare and Social Development

Ryazan, 390011, Russia

Location

SIH Leningrad Regional Oncology Dispensary

Saint Petersburg, 191104, Russia

Location

GUZ City Clinical Oncology Dispensary

Saint Petersburg, 197022, Russia

Location

St. Petersburg State Medical University I.P.Pavlov of Roszdrav

Saint Petersburg, 197022, Russia

Location

SIH Oncology Dispensary # 2 Of Department of Public Health

Sochi, 354057, Russia

Location

Republican Clinical Oncology Dispensary of Ministry of Healthcare of Bashkortostan Republic

Ufa, 450054, Russia

Location

Institute of Oncology and Radiology of Serbia

Belgrade, 11000, Serbia

Location

Klinicko Bolnicki Centar (KBC) Bezanijska Kosa (Medical Centre ''Bezanijska Kosa'' (MCBK))

Belgrade, 11000, Serbia

Location

Johns Hopkins Singapore International Medical Centre

Singapore, 308433, Singapore

Location

Institute for Oncology Department for Medical Oncology

Ljubljana, 1000, Slovenia

Location

The Medical Oncology Centre of Rosebank

Johannesburg, Gauteng, 2196, South Africa

Location

Eastleigh Breast Care Centre

Lynnwood, Gauteng, 0081, South Africa

Location

Hopelands Oncology Centre

Durban, KwaZulu-Natal, 4001, South Africa

Location

GVI Oncology Trial Unit Room 110 Panorama Medical Centre

Kraaifontein, Western Cape, South Africa

Location

National Cancer Center

Goyang-si, Gyeonggi-do, 410-769, South Korea

Location

Samsung Medical Center

Seoul, Korea, 135-710, South Korea

Location

Yonsei University Health System - Severance Hospital

Seoul, 120-752, South Korea

Location

Asan Medical Center

Seoul, 138-736, South Korea

Location

Hospital Germans Trias i Pujol Servicio de Oncologia

Badalona, Barcelona, 08916, Spain

Location

Corporacio Sanitaria Parc Tauli Servicio de Oncologia

Sabadell, Barcelona, 08208, Spain

Location

Hospital Mutua de Terrassa Servicio de Oncologia

Terrassa, Barcelona, 08221, Spain

Location

Hospital Central de Asturias Servicio de Oncologia, Planta Baja Oeste, Edificio Principal

Oviedo, Principality of Asturias, 33006, Spain

Location

Complejo Hospitalario U. de A Coruña Hospital Teresa Herrera Servicio de Oncologia

A Coruña, 15006, Spain

Location

Hospital General Universitario de Alicante Servicio de Oncologia

Alicante, 03010, Spain

Location

Hospital San Pedro de Alcantara Servicio de Oncologia

Cáceres, 10003, Spain

Location

Hospital Provincial (Reina Sofia) Servicio de Oncologia

Córdoba, 14004, Spain

Location

Hospital Universitario Dr. Josep Trueta Servicio de Oncologia

Girona, 17007, Spain

Location

Centro Hospitalario de Jaen Servicio de Oncologia

Jaén, 23007, Spain

Location

Hospital Gregorio Marañon Servicio de Oncologia

Madrid, 28007, Spain

Location

Centro Oncologico M.D. Anderson Internacional

Madrid, 28033, Spain

Location

Instituto Valenciano de Oncologia Servicio de Oncologia

Valencia, 46009, Spain

Location

Hospital Clinico Universitario de Valencia Servicio de Hematologia y Oncologia

Valencia, 46010, Spain

Location

Hospital Universitario Miguel Servet Servicio de Oncologia

Zaragoza, 50009, Spain

Location

University of Lausanne Hospitals CHUV

Lausanne, 1011, Switzerland

Location

Kantonsspital Winterthur Medizinische Onkologie

Winterthur, 8401, Switzerland

Location

Abteilung fuer Onkologie Departement für Innere

Zurich, CH-8091, Switzerland

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Division of Medical Oncology, Department of Medicine

Bangkok Noi, Bangkok, 10700, Thailand

Location

Broomfield Hospital

Chelmsford, Essex, CM1 7ET, United Kingdom

Location

Royal Marsden NHS Foundation Trust & Institute of Cancer Research

London, SW3 6JJ, United Kingdom

Location

The Royal Marsden NHS Foundation Trust & Institute of Cancer Research

London, SW3 6JJ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 23953056 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

neratinib; Lapatinib; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

Pharmacokinetic Analyses not included here; they are part of a population PK analysis.

Results Point of Contact

• Title: Senior Director, Clinical Operations
• Organization: Puma Biotechnology, Inc.

clinicaltrials@pumabiotechnology.com

+1 (424) 248-6500

Study Officials

• Puma

  Biotechnology

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2008
• First Posted: October 22, 2008
• Study Start: February 4, 2009
• Primary Completion: March 1, 2011
• Study Completion: June 3, 2018
• Last Updated: August 9, 2018
• Results First Posted: November 9, 2017

Record last verified: 2018-07

Locations

AU (1); RO (4); HK (3); RU (9); SL (1); CZ (1); DE (2); SG (1); CH (3); GR (1); JP (20); BE (1); FR (4); JO (1); TW (1); PR (1); ME (1); ES (15); BU (3); SE (2); TH (1); ZA (4); GB (3); KR (4); IT (2); US (44); HU (6); PL (4); CR (3); CA (2)