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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00777101
• Other study ID #: 3144A2-3003 / B1891003
• Status: Completed
• Phase: Phase 2
• Start date: February 4, 2009
• Est. completion date: June 3, 2018

Study information

• Verified date: July 2018
• Source: Puma Biotechnology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 233
• Est. completion date: June 3, 2018
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Neratinib
Tablets 240 mg orally once per day until disease progression or unacceptable toxicity
• Lapatinib
Tablets 1250 mg orally once per day until disease progression or unacceptable toxicity.
• 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.

Locations

Country	Name	City	State
Australia	Medical Oncology Royal Adelaide Hospital	Adelaide	South Australia
Australia	Western Hospital	Footscray	Victoria
Australia	Mater Private Centre for HOCA	South Brisbane	Queensland
Australia	Mount Hospital	West Perth
Austria	AKH Wien Universitaetsklinik fuer Innere Medizin I Klinische Abteilung für Onkologie	Wien
Belgium	Institut Jules Bordet Unite du Chimiotherapie	Brussels
Bulgaria	District Dispensary for Oncology Diseases Internal Unit- Sofia EOOD, Dept. of Chemotherapy	Sofia
Bulgaria	UMHAT Tzaritza Yoanna	Sofia
Bulgaria	Interdistrict Dispensary for Oncology Diseases -Internal Unit- Department Oncotherapy and Palliative Care	Varna
Canada	Centre Hospitalier Affilie Universitaire de Quebec Hopital du St-Sacrement	Quebec
Canada	BC Cancer Agency - Vancouver Centre	Vancouver	British Columbia
Croatia	General Hospital Varazdin	Varazdin
Croatia	University Hospital Center Zagreb	Zagreb
Croatia	University Hospital Sestre Milosrdnice	Zagreb
Czechia	Fakultni nemocnice Olomouc Klinika onkologie	Olomouc
France	Centre Oscar Lambret Departement de senologie	Lille
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	CHU de Poitiers Service d'oncologie medicale	Poitiers
France	Institut Gustave ROUSSY Service de Pathologie mammaire	Villejuif
Germany	Universitaetsklinikum Hamburg-Eppendorf Klinik und Poliklinik fuer Gynaekologie	Hamburg
Germany	Nationales Centrum fuer Tumorerkrankungen Sektion Gynaekologische Onkologie	Heidelberg
Greece	Theagenio Anticancer Hospital of Thessaloniki	Thessaloníki
Hong Kong	Department of Clinical Oncology, Tuen Mun Hospital	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	UNIMED Medical Institute, Comprehensive Centre for Breast Diseases	Hong Kong
Hungary	Fovarosi Onkormanyzat Szent Janos Korhaza es Eszak-budai Egyesitett Korhazai, Onkologia	Budapest
Hungary	Orszagos Onkologiai Intezet "B" Belgyogyaszati osztaly	Budapest
Hungary	Bacs-Kiskun Megyei Korhaz Onkoradiologiai Kozpont	Kecskemet
Hungary	Josa Andras Oktatokorhaz / Onkoradiologiai Osztaly	Nyiregyhaza
Hungary	Szegedi Tudomanyegyetem Onkoterapias Klinika	Szeged
Hungary	Hospital of County Veszprem	Veszprem
Italy	Ospedale Misericordia e Dolce c/o UO Oncologia Medica	Prato
Italy	Istituto Regina Elena, Struttura Complessa Oncologia Medica A	Roma
Japan	Aichi Cancer Center	Aichi
Japan	Chiba Cancer Center	Chiba
Japan	National Cancer Center Hospital East	Chiba
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka
Japan	Hiroshima City Hospital	Hiroshima
Japan	Hyogo Cancer Center	Hyogo
Japan	Hakuaikai Medical Corporation Sagara Hospital	Kagoshima
Japan	Tokai University Hospital	Kanagawa
Japan	Kumamoto Municipal Hospital	Kumamoto
Japan	Kyoto University Hospital	Kyoto
Japan	Niigata Cancer Center Hospital	Niigata
Japan	National Hospital Organization Osaka National Hospital	Osaka
Japan	Saitama Cancer Center	Saitama
Japan	National Hospital Organization Hokkaido Cancer Center	Sapporo	Hokkaido
Japan	Shizuoka Cancer Center	Shizuoka
Japan	Jichi Medical University Hospital	Tochigi
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	Tokyo
Japan	National Cancer Center Hospital	Tsukiji	Tokyo
Jordan	King Hussein Cancer Centre	Amman
Korea, Republic of	National Cancer Center	Goyang-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul	Korea
Korea, Republic of	Yonsei University Health System - Severance Hospital	Seoul
Mexico	Oca Hospital / Monterrey International Research Center	Monterrey	Nuevo Leon
Poland	Bialostockie Centrum Onkologii im. M. Sklodowskiej-Curie w Bialymstoku Specjalistyczny Szpital Onkologiczn	Bialystok
Poland	Uniwersyteckie Centrum Kliniczne w Gdansku Klinika Onkologii i Radioterapii	Gdansk
Poland	Szpital Uniwersytecki w Krakowie Oddzial KIiniczny Kliniki Onkologii	Krakow
Poland	Centrum Onkologii Ziemi Lubelskiej im. SW. Jana z Dukli	Lublin
Puerto Rico	Metropolitan Oncology Center	San Juan
Romania	Institutul Oncologic "Prof. Dr. Alex. Trestioreanu"	Bucuresti
Romania	Spitalul Universitar de Urgenta	Bucuresti
Romania	Centrul de Oncologie Medicala	Iasi
Romania	Spitalul Clinic Judetean	Sibiu
Russian Federation	Russian Oncology Research Centre of RAMS	Moscow
Russian Federation	GUZ Perm Regional Oncology Dispensary	Perm
Russian Federation	Scientific Research Institute of Oncology N.N. Petrov	Pesochny	Saint Petersburg
Russian Federation	Ryazan State Medical University I.P.Pavlov of Federal Agency in Healthcare and Social Development	Ryazan
Russian Federation	GUZ City Clinical Oncology Dispensary	Saint Petersburg
Russian Federation	SIH Leningrad Regional Oncology Dispensary	Saint Petersburg
Russian Federation	St. Petersburg State Medical University I.P.Pavlov of Roszdrav	Saint Petersburg
Russian Federation	SIH Oncology Dispensary # 2 Of Department of Public Health	Sochi
Russian Federation	Republican Clinical Oncology Dispensary of Ministry of Healthcare of Bashkortostan Republic	Ufa
Serbia	Institute of Oncology and Radiology of Serbia	Belgrade
Serbia	Klinicko Bolnicki Centar (KBC) Bezanijska Kosa (Medical Centre ''Bezanijska Kosa'' (MCBK))	Belgrade
Singapore	Johns Hopkins Singapore International Medical Centre	Singapore
Slovenia	Institute for Oncology Department for Medical Oncology	Ljubljana
South Africa	Hopelands Oncology Centre	Durban	KwaZulu Natal
South Africa	The Medical Oncology Centre of Rosebank	Johannesburg	Gauteng
South Africa	GVI Oncology Trial Unit Room 110 Panorama Medical Centre	Kraaifontein	Western Cape Province
South Africa	Eastleigh Breast Care Centre	Lynnwood	Gauteng
Spain	Complejo Hospitalario U. de A Coruña Hospital Teresa Herrera Servicio de Oncologia	A Coruña
Spain	Hospital General Universitario de Alicante Servicio de Oncologia	Alicante
Spain	Hospital Germans Trias i Pujol Servicio de Oncologia	Badalona	Barcelona
Spain	Hospital San Pedro de Alcantara Servicio de Oncologia	Caceres
Spain	Hospital Provincial (Reina Sofia) Servicio de Oncologia	Cordoba
Spain	Hospital Universitario Dr. Josep Trueta Servicio de Oncologia	Gerona
Spain	Centro Hospitalario de Jaen Servicio de Oncologia	Jaen
Spain	Centro Oncologico M.D. Anderson Internacional	Madrid
Spain	Hospital Gregorio Marañon Servicio de Oncologia	Madrid
Spain	Hospital Central de Asturias Servicio de Oncologia, Planta Baja Oeste, Edificio Principal	Oviedo	Asturias
Spain	Corporacio Sanitaria Parc Tauli Servicio de Oncologia	Sabadell	Barcelona
Spain	Hospital Mutua de Terrassa Servicio de Oncologia	Terrassa	Barcelona
Spain	Hospital Clinico Universitario de Valencia Servicio de Hematologia y Oncologia	Valencia
Spain	Instituto Valenciano de Oncologia Servicio de Oncologia	Valencia
Spain	Hospital Universitario Miguel Servet Servicio de Oncologia	Zaragoza
Switzerland	University of Lausanne Hospitals CHUV	Lausanne
Switzerland	Kantonsspital Winterthur Medizinische Onkologie	Winterthur
Switzerland	Abteilung fuer Onkologie Departement für Innere	Zuerich
Taiwan	National Taiwan University Hospital	Taipei
Thailand	Division of Medical Oncology, Department of Medicine	Bangkok-noi	Bangkok
United Kingdom	Broomfield Hospital	Chelmsford	Essex
United Kingdom	Royal Marsden NHS Foundation Trust & Institute of Cancer Research	London
United Kingdom	The Royal Marsden NHS Foundation Trust & Institute of Cancer Research	London
United States	Ashland-Bellefonte Cancer Center	Ashland	Kentucky
United States	Texas Oncology, P.A.	Austin	Texas
United States	Palm Beach Institute of Hematology & Oncology	Boynton Beach	Florida
United States	Oncology Partners Network	Cincinnati	Ohio
United States	MetroHealth Medical Center, Cancer Care Center	Cleveland	Ohio
United States	Missouri Cancer Associates	Columbia	Missouri
United States	Cookeville Regional Medical Center	Cookeville	Tennessee
United States	Cancer Care Specialists Of Central Illinois	Decatur	Illinois
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	El Paso Cancer Treatment Center - West	El Paso	Texas
United States	Central Indiana Cancer Centers	Fishers	Indiana
United States	The Center for Cancer and Blood Disorders	Fort Worth	Texas
United States	Robert R. Carroll, MD, PA	Gainesville	Florida
United States	Hematology Oncology of Indiana	Indianapolis	Indiana
United States	University of Florida	Jacksonville	Florida
United States	Capitol Comprehensive Cancer Care Clinic	Jefferson City	Missouri
United States	Center for Biomedical Research	Knoxville	Tennessee
United States	Thompson Cancer Survival Center Thompson Oncology Group	Knoxville	Tennessee
United States	Arena Oncology Associates, PC	Lake Success	New York
United States	Lancaster Cancer Center	Lancaster	Pennsylvania
United States	Owsley Brown Frazier Cancer Center (OBFCC)	Louisville	Kentucky
United States	Hematology Oncology Associates	Loxahatchee Groves	Florida
United States	University of Tennessee Cancer Institute	Memphis	Tennessee
United States	Mercy Research Institute	Miami	Florida
United States	Southwest Cancer Care	Murrieta	California
United States	Floyd Memorial Cancer Center of Indiana	New Albany	Indiana
United States	Weill Cornell Medical College New York-Presbyterian Hospital Weill, Cornell Breast Center	New York	New York
United States	University of Oklahoma Health Sciences Center Dept. of Hematology Oncology	Oklahoma City	Oklahoma
United States	UC Irvine Medical Center	Orange	California
United States	Cancer Centers of Florida	Orlando	Florida
United States	Purchase Cancer Group	Paducah	Kentucky
United States	Aptium Oncology/Comprehensive Cancer Center at Desert Regional Medical Center	Palm Springs	California
United States	Oncology Specialists, SC	Park Ridge	Illinois
United States	Allegheny General Hospital Allegheny Cancer Center	Pittsburgh	Pennsylvania
United States	Hematology Oncology Associates of the Treasure Coast	Port Saint Lucie	Florida
United States	Northwest Cancer Specialists, PC	Portland	Oregon
United States	HOPE Oncology	Richardson	Texas
United States	Cancer Care Network of South Texas-HOAST	San Antonio	Texas
United States	Redwood Regional Medical Group, Inc.	Santa Rosa	California
United States	Hematology Oncology Associates, P.C.	Stamford	Connecticut
United States	New York Oncology Hematolgy, PC	Troy	New York
United States	Arizona Oncology Associates HOPE	Tucson	Arizona
United States	East Texas Medical Center Cancer Institute, Tyler Hematology Oncology	Tyler	Texas
United States	Midwestern Regional Medical Center	Zion	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Puma Biotechnology, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  Croatia,  Czechia,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Italy,  Japan,  Jordan,  Korea, Republic of,  Mexico,  Poland,  Puerto Rico,  Romania,  Russian Federation,  Serbia,  Singapore,  Slovenia,  South Africa,  Spain,  Switzerland,  Taiwan,  Thailand,  United Kingdom, 

Outcome

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