Study Evaluating Neratinib Plus Paclitaxel VS Trastuzumab Plus Paclitaxel In ErbB-2 Positive Advanced Breast Cancer

Breast Cancer Clinical Trial

— NEFERTT  

Official title:

A Randomized, Open-Label, Two-Arm Study Of Neratinib Plus Paclitaxel Versus Trastuzumab Plus Paclitaxel As First-Line Treatment For ErbB-2-Positive Locally Recurrent Or Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00915018
• Other study ID #: 3144A2-3005 / B1891005
• Status: Completed
• Phase: Phase 2
• Start date: August 21, 2009
• Est. completion date: June 28, 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 study is investigating the effects of an experimental drug (neratinib) in combination with paclitaxel versus trastuzumab in combination with paclitaxel for the treatment of women who have not received previous treatment for erbB-2-positive locally recurrent or metastatic breast cancer. The study will compare the effectiveness of each regimen in shrinking tumors and extending the lives of women with erbB-2 (HER2) positive breast cancer. The study will also compare the safety of the two regimens and as well as the quality of life of subjects receiving either regimen.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 479
• Est. completion date: June 28, 2018
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• ErbB-2 positive locally recurrent or metastatic breast cancer

• Eastern Cooperative Oncology Group (ECOG) 0-2

• Measurable disease

• Availability of tumor tissue for HER2 status confirmation

Exclusion Criteria:

• Prior systemic anti-cancer therapy other than endocrine therapy for locally recurrent or metastatic disease

• Prior erbB-2 inhibitor other than trastuzumab or lapatinib in the neoadjuvant or adjuvant setting

• Progression/recurrence within 12 months after completion of adjuvant or neoadjuvant therapy

• History of heart disease

• History of gastrointestinal disease

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Neratinib
Neratinib - 240 mg orally daily, administered once daily. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.
• Trastuzumab
Trastuzumab - 4 mg/kg IV initial loading dose followed by subsequent once weekly doses of 2mg/kg IV. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.
• Paclitaxel
Paclitaxel - 80 mg/m² IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.

Locations

Country	Name	City	State
Australia	The Queen Elizabeth Hospital	North Adelaide	South Australia
Australia	Royal Melbourne Hospital	Parkville	Victoria
Bahamas	Affinity Research Limited	Nassau	CB
Belarus	Institution Gomel Regional Clinical Oncology Dispensary	Gomel
Belarus	Institution of Healthcare Grodno Regional Clinical Hospital	Grodno
Belarus	N.N. Aleksandrov National Cancer Center of Belarus	Lesnoy	Minsk Region
Belarus	Healthcare Institution Vitebsk Regional Clinical Oncology Dispensary	Vitebsk
Belgium	Institut Jules Bordet	Brussels
Bulgaria	District Dispensary for Oncology Diseases Internal Unit- Plovdiv EOOD	Plovdiv
Bulgaria	District Dispensary for Oncology Diseases Internal Unit- Sofia EOOD	Sofia
Bulgaria	Specialised Hospital of ActiveTreatment in Oncology, Clinic of Chemotherapy	Sofia
Canada	Hopital Charles, LeMoyne Le Centre Intégré de Cancérologie de la Montérégie	Greenfield Park	Quebec
Canada	Centre Hospitalier Régional de Trois-Rivières	Trois-Rivieres	Quebec
China	Cancer Hospital, Chinese Academy of Medical Sciences	Beijing
China	Chinese People's Liberation Army General Hospital	Beijing
China	Peking Union Medical College Hospital of Chinese Academy of Medical Sciences	Beijing
China	The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army	Beijing
China	Southern Medical University Nanfang Hospital	Guangzhou	Guangdong
China	Sun Yat-Sen University Cancer Center	Guangzhou	Guangdong
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Fudan University Shanghai Cancer Center	Shanghai
China	Tianjin Cancer Hospital	Tian Jin
Croatia	Clinical Hospital Osijek, Department of Radiotherapy and Oncology	Osijek
Croatia	University Hospital For Tumors	Zagreb
Denmark	Rigshospitalet, Copenhagen, Onkologisk Klinik	Copenhagen
France	Hôpital Henri-Mondor	Creteil
France	Centre Leon Berard Departement de Cancerologie Medicale	Lyon
France	Centre Val d'Aurelle	Montpellier
France	Groupe Hospitalier Paris Saint Joseph, Oncologie medicale	Paris
France	Hopital Hotel Dieu, Service d'Oncologie Medicale, Bat B2, 5ieme	Paris
France	Hopital La Pitie-Salpetriere	Paris
France	Service d'Oncologie et de Radiotherapie, Polyclinique Francheville	Perigueux
France	Clinique Armoricaine de Radiologie	St. Brieuc
France	Centre de Radiothérapie, Clinique Sainte Anne, Service d'Oncologie Libérale	Strasbourg
France	CHU Strasbourg Departement Oncologie & Hematologie Hopital Civil	Strasbourg
France	CHU Bretonneau, Centre Henry Kaplan	Tours
Germany	Sozialstiftung Bamberg Klinik fuer Haematologie und internistische Onkologie	Bamberg
Hong Kong	Pamela Youde Nethersole Eastern Hospital	Chai Wan
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	UNIMED Medical Institute, Comprehensive Centre for Breast Diseases	Wanchai
Hungary	Fovarosi Onkormanyzat Szent Imre Korhaz Klinikai Onkologiai Profil	Budapest
Hungary	Orszagos Onkologiai Intezet "B" Belgyogyaszati osztaly	Budapest
Hungary	Semmelweis Egyetem Radiologiai és Onkoterapias Klinika	Budapest
Hungary	Kaposi Mor Oktato Korhoz Onkologiai Centrum	Kaposvar
Hungary	Bacs-Kiskun Megyei Onkormanyzat Korhaza Onkoradiologiai Kozpont	Kecskemet
Hungary	Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház	Miskolc
Hungary	Szegedi Tudomanyegyetem Onkoterapias Klinika	Szeged
India	Jawaharlal Nehru Cancer Hospital	Bhopal	Madhya Pradesh
India	Searoc Cancer Center	Jaipur	Rajasthan
India	B P Poddar and Medical Research Ltd.	Kolkata	West Bengal
India	Meenakshi Mission Hospital and Research Centre	Madurai	Tamil Nadu
India	Tata Memorial Centre	Mumbai	Maharashtra
India	Central India Cancer Research Institute	Nagpur	Maharashtra
India	Curie Manavata Cancer Centre	Nashik	Maharashtra
India	Shatabdi Super Speciality Hospital	Nashilk	Maharashtra
India	Institute Rotary Cancer Hospital, AIIMS	New Delhi	Delhi
India	Deenanath Mangeshkar Hospital and Research Centre	Pune	Maharashtra
Israel	Kaplan Medical Center	Rehovot
Israel	Sourasky Medical Center	Tel Aviv
Israel	Assaf Harofeh Medical Center	Zerifin
Italy	Policlinico di Modena Oncologia ed Ematologia	Modena
Italy	Fondazione Salvatore Maugeri	Pavia
Italy	Ospedale San Pietro Fatebenefratelli	Roma
Italy	Policlinico Universitario Campus Bio-Medico	Roma
Italy	Ospedale San Giovanni Battista-Molinette	Torino
Japan	Aichi Cancer Center	Aichi	Nagoya-shi
Japan	National Hospital Organization Nagoya Medical Center	Aichi	Nagoya
Japan	Chiba Cancer Center	Chiba	Chiba-shi
Japan	National Cancer Center Hospital East	Chiba	Kashiwa-shi
Japan	National Hospital Organization Shikoku Cancer Center	Ehime	Matsuyama-city
Japan	Kurume Daiichi Social Insurance Hospital	Fukuoka	Kurume-Shi
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka	Fukuoka-shi
Japan	Hiroshima City Hospital	Hiroshima
Japan	Hiroshima University Hospital	Hiroshima	Hiroshima-shi
Japan	National Hospital Organization Kure Medical Center and Chugoku Cancer Center	Hiroshima
Japan	National Hospital Organization Hokkaido Cancer Center	Hokkaido	Sapporo-shi
Japan	Hyogo Cancer Center	Hyogo	Akashi-shi
Japan	Kobe City Medical Center General Hospital	Hyogo
Japan	Shinko Hospital	Hyogo
Japan	National Hospital Organization Mito Medical Center	Ibaraki	Higashiibaraki-gun
Japan	Iwate Medical University Hospital	Iwate	Morioka-shi
Japan	Hakuaikai Medical Corporation Sagara Hospital	Kagoshima	Kagoshima-city
Japan	Kanagawa Cancer Center	Kanagawa	Yokohama-City
Japan	Kumamoto Municipal Hospital	Kumamoto	Kumamoto-city
Japan	Kumamoto University Hospital	Kumamoto
Japan	Tohoku University Hospital	Miyagi	Sendai-city
Japan	Tenri Hospital	Nara	Tenri-shi
Japan	Niigata Cancer Center Hospital	Niigata	Niigata-shi
Japan	National Hospital Organization Beppu Medical Center	Oita	Beppu-shi
Japan	National Hospital Organization Osaka National Hospital	Osaka	Osaka-shi
Japan	Osaka Medical Center for Cancer and Cardiovascular Diseases	Osaka	Osaka-shi
Japan	Osaka University Hospital	Osaka
Japan	Tazuke Kofukai Medical Research Institute Kitano Hospital	Osaka
Japan	Saitama Cancer Center	Saitama	Kitaadachi-gun
Japan	Jichi Medical University Hospital	Tochigi
Japan	National Hospital Organization Tokyo Medical Center	Tokyo
Japan	Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital	Tokyo	Bunkyo-ku
Japan	Toranomon Hospital	Tokyo
Korea, Republic of	National Cancer Center, Center for Breast Cancer	Goyang-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul	Korea
Korea, Republic of	Korea University Guro Hospital	Seoul	Korea
Korea, Republic of	Samsung Medical Center	Seoul	Korea
Korea, Republic of	Yonsei University Health System Severance Hospital	Seoul	Seoul/Korea
Latvia	Piejuras Hospital, Liepajas Oncological Clinic	Liepaja
Latvia	Pauls Stradinš Clinical University Hospital	Riga
Latvia	Riga Eastern University Hospital	Riga
Lithuania	Hospital of Lithuanian University of Health sciences	Kaunas
Lithuania	Nacionalinis Vezio Institutas, Vilniaus Universiteto Onkologijos Institutas	Vilnius
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malta	Sir Anthony Oncology Center	Floriana
Poland	Bialostockie Centrum Onkologii	Bialystok
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Wojewodzki Oddzial	Jelenia Gora	Dolnoslaskie
Poland	Zaklad Opieki Zdrowotnej MSW z Warminsko, Mazurskim Centrum Onkologii	Olsztyn	Warminsko-Mazurskie
Poland	Opolskie Centrum Onkologii	Opole	Opolskie
Poland	Magodent	Warszawa	Mazowieckie
Portugal	Hospital da Luz Servico de Oncologia Medica	Lisboa
Romania	Spitalul Universitar de Urgenta Bucuresti	Bucuresti
Romania	Institutul Oncologic Prof. Dr. Ion Chiricuta	Cluj-Napoca	Cluj
Romania	SC Oncolab S.R.L.	Craiova	Dolj
Serbia	Institute of Oncology and Radiology of Serbia	Belgrade
Serbia	Clinical centre Nis Clinic of Oncology	Nis
Singapore	National Cancer Centre Singapore	Singapore
Singapore	National University Hospital, National Cancer Institute	Singapore
South Africa	Westridge Medical Centre	Durban	KwaZulu Natal
South Africa	Sandton Oncology Centre	Johannesburg	Gauteng
South Africa	The Medical Oncology Centre of Rosebank	Johannesburg	Gauteng
South Africa	University of Witwatersrand Oncology, Donald Gordon Medical Centre	Johannesburg	Gauteng
South Africa	GVI Oncology	Kraaifontein	Western Cape
South Africa	GVI Oncology	Port Elizabeth	Eastern Cape
South Africa	Eastleigh Breast Care Centre	Pretoria	Gauteng
Spain	Hospital Universitario Fundación Alcorcón	Alcorcon	Madrid
Spain	Hospital de Cruces	Baracaldo	Vizcaya
Spain	Hospital Universitari Arnau de Vilanova	Lleida	Cataluna
Spain	Centro Oncologico MD Anderson	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Puerta De Hierro	Majadahonda	Madrid
Spain	Hospital Costa del Sol	Marbella	Malaga
Spain	Hospital Son Llàtzer	Palma	Illes Balears
Spain	Hospital Universitario Infanta Cristina	Parla	Madrid
Spain	Hospital Madrid Norte Sanchinarro Centro Integral Oncológico Clara Campal Ensayos Clínicos	Sanchinarro	Madrid
Spain	Complejo Hospitalario Universitario Santiago de Compostela	Santiago de Compostela	Galicia
Switzerland	Tumor Center Hirslanden Medical Center	Aarau
Switzerland	Spital STS AG Onkologiezentrum Thun - Berner Oberland	Thun
Switzerland	Kantonsspital Winterthur Medizinische Onkologie	Winterthur
Taiwan	Chang Gung Medical Foundation, Linkou Branch	Taoyuan
Turkey	Ege Universitesi Tip Fakultesi Tulay Aktas Onkoloji Hastanesi	Bornova	Izmir
Ukraine	Komunalnyy Zaklad Cherkasskyy Oblasnyy Onkologichnyy Dyspanser	Cherkassy
Ukraine	Chernivtsi Regional Oncology Centre Outpatient Department Bukovynian State Medical University Department of Oncology and Radiology	Chernivtsi
Ukraine	City Multifield Clinical Hospital	Dnipropetrovsk
Ukraine	Donetsk Regional Antitumor Center Department of Pretumor Diseases and Tumor Treatment	Donetsk
Ukraine	S.P. Grigoreva Institute of Medical Radiology Department of Chemotherapy	Kharkiv
Ukraine	National Institute of Cancer Department of Conseravtive Methods of Treatment	Kyiv
Ukraine	Volyn Regional Oncological Center	Lutsk
Ukraine	State Oncological Regional Treatment and Diagnostic Center	Lviv
Ukraine	Mariupil Oncological Center	Mariupil
Ukraine	Sumy Regional Clinical Oncology Centre	Sumy
United Kingdom	Guy's and St Thomas NHS Foundation Trust Management Offices 4th Floor Bermondsey Wing Guy's Hospital	London
United Kingdom	Nottingham University Hospital	Nottingham
United States	Summa Health System Hospitals	Akron	Ohio
United States	Phoebe Cancer Center	Albany	Georgia
United States	CHRISTUS St. Frances Cabrini Hospital	Alexandria	Louisiana
United States	Texas Oncology	Bedford	Texas
United States	Palm Beach Institute of Hematology and Oncology	Boynton Beach	Florida
United States	Charleston Area Medical Center, Health, Education, and Research Institute	Charleston	West Virginia
United States	Medical University of South Carolina Hollings Cancer Center	Charleston	South Carolina
United States	Missouri Cancer Associates	Columbia	Missouri
United States	Samaritan Hematology and Oncology Consultants	Corvallis	Oregon
United States	North Broward Medical Center Cancer Center	Deerfield Beach	Florida
United States	Dublin Hematology and Oncology Care	Dublin	Georgia
United States	El Paso Cancer Treatment Center	El Paso	Texas
United States	Broward General Medical Center	Fort Lauderdale	Florida
United States	Gaston Hematology and Oncology Associates	Gastonia	North Carolina
United States	Tenessee Cancer Specialists	Knoxville	Tennessee
United States	Family Cancer Care	Memphis	Tennessee
United States	Hematology Oncology Services	Metairie	Louisiana
United States	Texas Oncology-Allison Cancer Center	Midland	Texas
United States	Mid Florida Cancer Centers	Orange City	Florida
United States	Ventura County Hematology-Oncology Specialists	Oxnard	California
United States	The Valley Hospital, Luckow Pavilion Office of Oncology Clinical Trials	Paramus	New Jersey
United States	Pawtucket Memorial Hospital	Pawtucket	Rhode Island
United States	Cancer Center of Central Connecticut	Plainville	Connecticut
United States	Florida Cancer Research Institute	Plantation	Florida
United States	Hematology Oncology Associates of Treasure Coast	Port Saint Lucie	Florida
United States	Washington University School of Medicine Siteman Cancer Center	Saint Louis	Missouri
United States	Park Nicollet Institute	Saint Louis Park	Minnesota
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	Redwood Regional Medical Group	Santa Rosa	California
United States	Clintell	Skokie	Illinois
United States	Presence Hematology and Oncology	Skokie	Illinois
United States	Southlake Oncology	Southlake	Texas
United States	Springfield Clinic	Springfield	Illinois
United States	St. John's Medical Research Institute	Springfield	Missouri
United States	Santee Hematology Oncology	Sumter	South Carolina
United States	Warren Cancer Research Foundation	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Puma Biotechnology, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Bahamas,  Belarus,  Belgium,  Bulgaria,  Canada,  China,  Croatia,  Denmark,  France,  Germany,  Hong Kong,  Hungary,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Latvia,  Lithuania,  Malaysia,  Malta,  Poland,  Portugal,  Romania,  Serbia,  Singapore,  South Africa,  Spain,  Switzerland,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival	Defined as the interval from the date of randomization until the first date on which recurrence or progression, or death due to any cause, is documented, censored at the last assessable evaluation or at the initiation of new anticancer therapy.	From randomization to disease progression or death, assessed up to 5.3 years
Secondary	Objective Response Rate	Defined as the percentage of subjects who achieved confirmed tumor response (complete or partial 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; and Non-Progressive Disease for non-target lesions, and no new lesions.	From randomization to disease progression or last tumor assessment, assessed up to 5.3 years
Secondary	Duration of Response	Measured from the time at which measurement criteria were first met for CR or PR (whichever status was recorded first), until the date of first recurrence, disease progression (PD), or death was objectively documented, taking as a reference for PD the smallest measurements recorded since enrollment, 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; and Non-PD for non-target lesions, and no new lesions.	From first response to first PD or death, assessed up to 5.3 years after first subject randomized
Secondary	Clinical Benefit Rate	Defined as the proportion of patients who achieved overall tumor response (CR or PR) or SD for at least 24 weeks 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; and Non-PD for non-target lesions, and no new 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.	From randomization to disease progression or death, assessed up to 5.3 years
Secondary	Symptomatic or Progressive Central Nervous System (CNS) Lesions	Defined as the time interval from the date of randomization until the first date of CNS symptoms, the imaging examination shows CNS progression or is censored at the last assessable evaluation on study or prior to new anti-cancer therapy, if applicable.; If median time to Symptomatic or Progressive CNS Lesions is not estimable, cumulative incidence will be reported instead.	From randomization to disease progression PD or last tumor assessment, assessed up to 5.3 years