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

• Sponsor: Puma Biotechnology, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00915018
• Collaborator: (none)
• Enrollment: 479
• Locations: 195
• Arms: 2
• Actual Duration (Months): 106.2
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Neratinib; Drug: Trastuzumab; Drug: Paclitaxel	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 479 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Aug 21, 2009
• Actual Primary Completion Date: Aug 1, 2013
• Actual Study Completion Date: Jun 28, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: neratinib plus paclitaxel	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.; Drug: 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.; Other Names: Taxol Abraxane Onxol Nov-onxol
Active Comparator: trastuzumab plus paclitaxel	Drug: 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.; Other Names: Herceptin Herclon ; Drug: 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.; Other Names: Taxol Abraxane Onxol Nov-onxol

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival [From randomization to disease progression or death, assessed up to 5.3 years]

   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.

Secondary Outcome Measures

1. Objective Response Rate [From randomization to disease progression or last tumor assessment, assessed up to 5.3 years]

   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.

2. Duration of Response [From first response to first PD or death, assessed up to 5.3 years after first subject randomized]

   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.

3. Clinical Benefit Rate [From randomization to disease progression or death, assessed up to 5.3 years]

   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.

4. Symptomatic or Progressive Central Nervous System (CNS) Lesions [From randomization to disease progression PD or last tumor assessment, assessed up to 5.3 years]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ventura County Hematology-Oncology Specialists	Oxnard	California	United States	93030
2	Redwood Regional Medical Group	Santa Rosa	California	United States	95403
3	Cancer Center of Central Connecticut	Plainville	Connecticut	United States	06062
4	Palm Beach Institute of Hematology and Oncology	Boynton Beach	Florida	United States	33435
5	North Broward Medical Center Cancer Center	Deerfield Beach	Florida	United States	33064
6	Broward General Medical Center	Fort Lauderdale	Florida	United States	33316
7	Mid Florida Cancer Centers	Orange City	Florida	United States	32763
8	Florida Cancer Research Institute	Plantation	Florida	United States	33324
9	Hematology Oncology Associates of Treasure Coast	Port Saint Lucie	Florida	United States	34952
10	Phoebe Cancer Center	Albany	Georgia	United States	31701
11	Dublin Hematology and Oncology Care	Dublin	Georgia	United States	31021
12	Clintell	Skokie	Illinois	United States	60077
13	Presence Hematology and Oncology	Skokie	Illinois	United States	60077
14	Springfield Clinic	Springfield	Illinois	United States	62703
15	CHRISTUS St. Frances Cabrini Hospital	Alexandria	Louisiana	United States	71301
16	Hematology Oncology Services	Metairie	Louisiana	United States	70006
17	Park Nicollet Institute	Saint Louis Park	Minnesota	United States	55426
18	Missouri Cancer Associates	Columbia	Missouri	United States	65201
19	Washington University School of Medicine Siteman Cancer Center	Saint Louis	Missouri	United States	63110
20	St. John's Medical Research Institute	Springfield	Missouri	United States	65807
21	The Valley Hospital, Luckow Pavilion Office of Oncology Clinical Trials	Paramus	New Jersey	United States	07652
22	Gaston Hematology and Oncology Associates	Gastonia	North Carolina	United States	28054
23	Summa Health System Hospitals	Akron	Ohio	United States	44304-1619
24	Warren Cancer Research Foundation	Tulsa	Oklahoma	United States	74104
25	Samaritan Hematology and Oncology Consultants	Corvallis	Oregon	United States	97330
26	Pawtucket Memorial Hospital	Pawtucket	Rhode Island	United States	02860
27	Medical University of South Carolina Hollings Cancer Center	Charleston	South Carolina	United States	29425
28	Santee Hematology Oncology	Sumter	South Carolina	United States	29150
29	Tenessee Cancer Specialists	Knoxville	Tennessee	United States	37909
30	Family Cancer Care	Memphis	Tennessee	United States	38120
31	Texas Oncology	Bedford	Texas	United States	76022
32	El Paso Cancer Treatment Center	El Paso	Texas	United States	79902
33	Texas Oncology-Allison Cancer Center	Midland	Texas	United States	79701
34	Southlake Oncology	Southlake	Texas	United States	76092
35	Utah Cancer Specialists	Salt Lake City	Utah	United States	84106
36	Charleston Area Medical Center, Health, Education, and Research Institute	Charleston	West Virginia	United States	25304
37	The Queen Elizabeth Hospital	North Adelaide	South Australia	Australia	5011
38	Royal Melbourne Hospital	Parkville	Victoria	Australia	3050
39	Affinity Research Limited	Nassau	CB	Bahamas	13932
40	N.N. Aleksandrov National Cancer Center of Belarus	Lesnoy	Minsk Region	Belarus	223040
41	Institution Gomel Regional Clinical Oncology Dispensary	Gomel		Belarus	246012
42	Institution of Healthcare Grodno Regional Clinical Hospital	Grodno		Belarus	230017
43	Healthcare Institution Vitebsk Regional Clinical Oncology Dispensary	Vitebsk		Belarus	210603
44	Institut Jules Bordet	Brussels		Belgium	1000
45	District Dispensary for Oncology Diseases Internal Unit- Plovdiv EOOD	Plovdiv		Bulgaria	4004
46	District Dispensary for Oncology Diseases Internal Unit- Sofia EOOD	Sofia		Bulgaria	1233
47	Specialised Hospital of ActiveTreatment in Oncology, Clinic of Chemotherapy	Sofia		Bulgaria	1756
48	Hopital Charles, LeMoyne Le Centre Intégré de Cancérologie de la Montérégie	Greenfield Park	Quebec	Canada	J4V 2H1
49	Centre Hospitalier Régional de Trois-Rivières	Trois-Rivieres	Quebec	Canada	G8Z 3R9
50	Sun Yat-Sen University Cancer Center	Guangzhou	Guangdong	China	510060
51	Southern Medical University Nanfang Hospital	Guangzhou	Guangdong	China	510515
52	Zhejiang Cancer Hospital	Hangzhou	Zhejiang	China	310022
53	Cancer Hospital, Chinese Academy of Medical Sciences	Beijing		China	100021
54	Peking Union Medical College Hospital of Chinese Academy of Medical Sciences	Beijing		China	100032
55	The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army	Beijing		China	100071
56	Chinese People's Liberation Army General Hospital	Beijing		China	100853
57	Fudan University Shanghai Cancer Center	Shanghai		China	200032
58	Tianjin Cancer Hospital	Tian Jin		China	300060
59	Clinical Hospital Osijek, Department of Radiotherapy and Oncology	Osijek		Croatia	31000
60	University Hospital For Tumors	Zagreb		Croatia	10000
61	Rigshospitalet, Copenhagen, Onkologisk Klinik	Copenhagen		Denmark	2100
62	Hôpital Henri-Mondor	Creteil		France	94010
63	Centre Leon Berard Departement de Cancerologie Medicale	Lyon		France	69373
64	Centre Val d'Aurelle	Montpellier		France	34298
65	Hopital Hotel Dieu, Service d'Oncologie Medicale, Bat B2, 5ieme	Paris		France	75181
66	Hopital La Pitie-Salpetriere	Paris		France	75651
67	Groupe Hospitalier Paris Saint Joseph, Oncologie medicale	Paris		France	75674
68	Service d'Oncologie et de Radiotherapie, Polyclinique Francheville	Perigueux		France	24004
69	Clinique Armoricaine de Radiologie	St. Brieuc		France	22015
70	Centre de Radiothérapie, Clinique Sainte Anne, Service d'Oncologie Libérale	Strasbourg		France	67000
71	CHU Strasbourg Departement Oncologie & Hematologie Hopital Civil	Strasbourg		France	67091
72	CHU Bretonneau, Centre Henry Kaplan	Tours		France	37044
73	Sozialstiftung Bamberg Klinik fuer Haematologie und internistische Onkologie	Bamberg		Germany	96049
74	Pamela Youde Nethersole Eastern Hospital	Chai Wan		Hong Kong
75	Queen Mary Hospital	Hong Kong		Hong Kong
76	UNIMED Medical Institute, Comprehensive Centre for Breast Diseases	Wanchai		Hong Kong
77	Semmelweis Egyetem Radiologiai és Onkoterapias Klinika	Budapest		Hungary	1082
78	Fovarosi Onkormanyzat Szent Imre Korhaz Klinikai Onkologiai Profil	Budapest		Hungary	1115
79	Orszagos Onkologiai Intezet "B" Belgyogyaszati osztaly	Budapest		Hungary	1122
80	Kaposi Mor Oktato Korhoz Onkologiai Centrum	Kaposvar		Hungary	7400
81	Bacs-Kiskun Megyei Onkormanyzat Korhaza Onkoradiologiai Kozpont	Kecskemet		Hungary	6000
82	Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház	Miskolc		Hungary	3526
83	Szegedi Tudomanyegyetem Onkoterapias Klinika	Szeged		Hungary	6720
84	Institute Rotary Cancer Hospital, AIIMS	New Delhi	Delhi	India	110029
85	Jawaharlal Nehru Cancer Hospital	Bhopal	Madhya Pradesh	India	462001
86	Tata Memorial Centre	Mumbai	Maharashtra	India	400012
87	Central India Cancer Research Institute	Nagpur	Maharashtra	India	440010
88	Curie Manavata Cancer Centre	Nashik	Maharashtra	India	422004
89	Shatabdi Super Speciality Hospital	Nashilk	Maharashtra	India	422005
90	Deenanath Mangeshkar Hospital and Research Centre	Pune	Maharashtra	India	411001
91	Searoc Cancer Center	Jaipur	Rajasthan	India	302013
92	Meenakshi Mission Hospital and Research Centre	Madurai	Tamil Nadu	India	625107
93	B P Poddar and Medical Research Ltd.	Kolkata	West Bengal	India	700053
94	Kaplan Medical Center	Rehovot		Israel	76101
95	Sourasky Medical Center	Tel Aviv		Israel	64239
96	Assaf Harofeh Medical Center	Zerifin		Israel	60930
97	Policlinico di Modena Oncologia ed Ematologia	Modena		Italy	41100
98	Fondazione Salvatore Maugeri	Pavia		Italy	27100
99	Policlinico Universitario Campus Bio-Medico	Roma		Italy	00128
100	Ospedale San Pietro Fatebenefratelli	Roma		Italy	00189
101	Ospedale San Giovanni Battista-Molinette	Torino		Italy	10126
102	Hyogo Cancer Center	Hyogo	Akashi-shi	Japan	673-8558
103	National Hospital Organization Beppu Medical Center	Oita	Beppu-shi	Japan	874-0011
104	Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital	Tokyo	Bunkyo-ku	Japan	113-8677
105	Chiba Cancer Center	Chiba	Chiba-shi	Japan	260-8717
106	National Hospital Organization Kyushu Cancer Center	Fukuoka	Fukuoka-shi	Japan	811-1395
107	National Hospital Organization Mito Medical Center	Ibaraki	Higashiibaraki-gun	Japan	311-3193
108	Hiroshima University Hospital	Hiroshima	Hiroshima-shi	Japan	734-8551
109	Hakuaikai Medical Corporation Sagara Hospital	Kagoshima	Kagoshima-city	Japan	892-0833
110	National Cancer Center Hospital East	Chiba	Kashiwa-shi	Japan	277-8577
111	Saitama Cancer Center	Saitama	Kitaadachi-gun	Japan	362-0806
112	Kumamoto Municipal Hospital	Kumamoto	Kumamoto-city	Japan	862-8505
113	Kurume Daiichi Social Insurance Hospital	Fukuoka	Kurume-Shi	Japan	830-0013
114	National Hospital Organization Shikoku Cancer Center	Ehime	Matsuyama-city	Japan	791-0280
115	Iwate Medical University Hospital	Iwate	Morioka-shi	Japan	020-8505
116	Aichi Cancer Center	Aichi	Nagoya-shi	Japan	464-8681
117	National Hospital Organization Nagoya Medical Center	Aichi	Nagoya	Japan	460-0001
118	Niigata Cancer Center Hospital	Niigata	Niigata-shi	Japan	951-8566
119	Osaka Medical Center for Cancer and Cardiovascular Diseases	Osaka	Osaka-shi	Japan	537-8511
120	National Hospital Organization Osaka National Hospital	Osaka	Osaka-shi	Japan	540-0006
121	National Hospital Organization Hokkaido Cancer Center	Hokkaido	Sapporo-shi	Japan	003-0804
122	Tohoku University Hospital	Miyagi	Sendai-city	Japan	980-8574
123	Tenri Hospital	Nara	Tenri-shi	Japan	632-8552
124	Kanagawa Cancer Center	Kanagawa	Yokohama-City	Japan	241-0815
125	Hiroshima City Hospital	Hiroshima		Japan	730-8518
126	National Hospital Organization Kure Medical Center and Chugoku Cancer Center	Hiroshima		Japan	737-0023
127	Kobe City Medical Center General Hospital	Hyogo		Japan	650-0047
128	Shinko Hospital	Hyogo		Japan	651-0072
129	Kumamoto University Hospital	Kumamoto		Japan	860-8556
130	Tazuke Kofukai Medical Research Institute Kitano Hospital	Osaka		Japan	530-8480
131	Osaka University Hospital	Osaka		Japan	565-0871
132	Jichi Medical University Hospital	Tochigi		Japan	329-0498
133	Toranomon Hospital	Tokyo		Japan	105-8470
134	National Hospital Organization Tokyo Medical Center	Tokyo		Japan	152-8902
135	National Cancer Center, Center for Breast Cancer	Goyang-si	Gyeonggi-do	Korea, Republic of	410-769
136	Samsung Medical Center	Seoul	Korea	Korea, Republic of	135-710
137	Asan Medical Center	Seoul	Korea	Korea, Republic of	138-736
138	Korea University Guro Hospital	Seoul	Korea	Korea, Republic of	152-703
139	Yonsei University Health System Severance Hospital	Seoul	Seoul/Korea	Korea, Republic of	120-752
140	Piejuras Hospital, Liepajas Oncological Clinic	Liepaja		Latvia	LV-3401
141	Pauls Stradiņš Clinical University Hospital	Riga		Latvia	LV - 1002
142	Riga Eastern University Hospital	Riga		Latvia	LV-1079
143	Hospital of Lithuanian University of Health sciences	Kaunas		Lithuania	LT 45434
144	Nacionalinis Vezio Institutas, Vilniaus Universiteto Onkologijos Institutas	Vilnius		Lithuania	LT-08660
145	University Malaya Medical Centre	Kuala Lumpur		Malaysia	59100
146	Sir Anthony Oncology Center	Floriana		Malta	VLT 14
147	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Wojewodzki Oddzial	Jelenia Gora	Dolnoslaskie	Poland	58-506
148	Magodent	Warszawa	Mazowieckie	Poland	04125
149	Opolskie Centrum Onkologii	Opole	Opolskie	Poland	45061
150	Zakład Opieki Zdrowotnej MSW z Warmińsko, Mazurskim Centrum Onkologii	Olsztyn	Warminsko-Mazurskie	Poland	10228
151	Białostockie Centrum Onkologii	Bialystok		Poland	15027
152	Hospital da Luz Servico de Oncologia Medica	Lisboa		Portugal	1500-650
153	Institutul Oncologic Prof. Dr. Ion Chiricuţă	Cluj-Napoca	Cluj	Romania	400015
154	SC Oncolab S.R.L.	Craiova	Dolj	Romania	200385
155	Spitalul Universitar de Urgenta Bucuresti	Bucuresti		Romania	050098
156	Institute of Oncology and Radiology of Serbia	Belgrade		Serbia	11000
157	Clinical centre Nis Clinic of Oncology	Nis		Serbia	18000
158	National University Hospital, National Cancer Institute	Singapore		Singapore	119082
159	National Cancer Centre Singapore	Singapore		Singapore	169610
160	GVI Oncology	Port Elizabeth	Eastern Cape	South Africa	6045
161	The Medical Oncology Centre of Rosebank	Johannesburg	Gauteng	South Africa	2196
162	University of Witwatersrand Oncology, Donald Gordon Medical Centre	Johannesburg	Gauteng	South Africa	2197
163	Sandton Oncology Centre	Johannesburg	Gauteng	South Africa	2199
164	Eastleigh Breast Care Centre	Pretoria	Gauteng	South Africa	0081
165	Westridge Medical Centre	Durban	KwaZulu Natal	South Africa	4001
166	GVI Oncology	Kraaifontein	Western Cape	South Africa	7570
167	Hospital Universitari Arnau de Vilanova	Lleida	Cataluna	Spain	25198
168	Complejo Hospitalario Universitario Santiago de Compostela	Santiago de Compostela	Galicia	Spain	15706
169	Hospital Son Llàtzer	Palma	Illes Balears	Spain	07198
170	Hospital Universitario Fundación Alcorcón	Alcorcon	Madrid	Spain	28922
171	Hospital Puerta De Hierro	Majadahonda	Madrid	Spain	28222
172	Hospital Universitario Infanta Cristina	Parla	Madrid	Spain	28981
173	Hospital Madrid Norte Sanchinarro Centro Integral Oncológico Clara Campal Ensayos Clínicos	Sanchinarro	Madrid	Spain	28050
174	Hospital Costa del Sol	Marbella	Malaga	Spain	29603
175	Hospital de Cruces	Baracaldo	Vizcaya	Spain	48903
176	Centro Oncologico MD Anderson	Madrid		Spain	28033
177	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
178	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
179	Tumor Center Hirslanden Medical Center	Aarau		Switzerland	5000
180	Spital STS AG Onkologiezentrum Thun - Berner Oberland	Thun		Switzerland	3600
181	Kantonsspital Winterthur Medizinische Onkologie	Winterthur		Switzerland	8401
182	Chang Gung Medical Foundation, Linkou Branch	Taoyuan		Taiwan	333
183	Ege Universitesi Tip Fakultesi Tulay Aktas Onkoloji Hastanesi	Bornova	Izmir	Turkey	35040
184	Komunalnyy Zaklad Cherkasskyy Oblasnyy Onkologichnyy Dyspanser	Cherkassy		Ukraine	18009
185	Chernivtsi Regional Oncology Centre Outpatient Department Bukovynian State Medical University Department of Oncology and Radiology	Chernivtsi		Ukraine	58013
186	City Multifield Clinical Hospital	Dnipropetrovsk		Ukraine	49102
187	Donetsk Regional Antitumor Center Department of Pretumor Diseases and Tumor Treatment	Donetsk		Ukraine	83092
188	S.P. Grigoreva Institute of Medical Radiology Department of Chemotherapy	Kharkiv		Ukraine	61024
189	National Institute of Cancer Department of Conseravtive Methods of Treatment	Kyiv		Ukraine	03022
190	Volyn Regional Oncological Center	Lutsk		Ukraine	63000
191	State Oncological Regional Treatment and Diagnostic Center	Lviv		Ukraine	79031
192	Mariupil Oncological Center	Mariupil		Ukraine	87500
193	Sumy Regional Clinical Oncology Centre	Sumy		Ukraine	40005
194	Guy's and St Thomas NHS Foundation Trust Management Offices 4th Floor Bermondsey Wing Guy's Hospital	London		United Kingdom	SE1 9RT
195	Nottingham University Hospital	Nottingham		United Kingdom	NG5 1PB

Sponsors and Collaborators

• Puma Biotechnology, Inc.

Investigators

• Study Director: Puma, Biotechnology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Puma Biotechnology, Inc.
• ClinicalTrials.gov Identifier: NCT00915018
• Other Study ID Numbers: 3144A2-3005 / B1891005
• First Posted: Jun 5, 2009
• Last Update Posted: Aug 22, 2018
• Last Verified: Jul 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Puma Biotechnology, Inc.: ErbB-2 positive advanced breast cancer; HKI-272; Neratinib; Nerlynx; HER2; PB-272; metastatic breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Paclitaxel; Trastuzumab; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Arm/Group Title	Neratinib + Paclitaxel	Trastuzumab + Paclitaxel
Arm/Group Description	Neratinib + Paclitaxel 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. 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.	Trastuzumab + Paclitaxel Trastuzumab: Trastuzumab - 4 mg/kg IV initial loading dose followed by subsequent once weekly doses of 2 mg/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.
Period Title: Overall Study
STARTED	242	237
Received Treatment	240	234
COMPLETED	27	30
NOT COMPLETED	215	207

Baseline Characteristics

Arm/Group Title	Neratinib + Paclitaxel	Trastuzumab + Paclitaxel	Total
Arm/Group Description	Neratinib + Paclitaxel 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. 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.	Trastuzumab + Paclitaxel Trastuzumab: Trastuzumab - 4 mg/kg IV initial loading dose followed by subsequent once weekly doses of 2 mg/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.	Total of all reporting groups
Overall Participants	242	237	479
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	199 82.2%	193 81.4%	392 81.8%
>=65 years	43 17.8%	44 18.6%	87 18.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.0 (11.6)	54.3 (11.0)	54.1 (11.3)
Sex: Female, Male (Count of Participants)
Female	242 100%	237 100%	479 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival
Description	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.
Time Frame	From randomization to disease progression or death, assessed up to 5.3 years

Outcome Measure Data

Analysis Population Description

all randomized patients

Arm/Group Title	Neratinib + Paclitaxel	Trastuzumab + Paclitaxel
Arm/Group Description	Neratinib + Paclitaxel 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. 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.	Trastuzumab + Paclitaxel Trastuzumab: Trastuzumab - 4 mg/kg IV initial loading dose followed by subsequent once weekly doses of 2 mg/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.
Measure Participants	242	237
Median (95% Confidence Interval) [months]	12.9	12.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neratinib + Paclitaxel, Trastuzumab + Paclitaxel
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8934
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.015
	Confidence Interval	(2-Sided) 95%; 0.813 to 1.269
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Objective Response Rate
Description	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.
Time Frame	From randomization to disease progression or last tumor assessment, assessed up to 5.3 years

Outcome Measure Data

Analysis Population Description

all randomized patients

Arm/Group Title	Neratinib + Paclitaxel	Trastuzumab + Paclitaxel
Arm/Group Description	Neratinib + Paclitaxel 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. 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.	Trastuzumab + Paclitaxel Trastuzumab: Trastuzumab - 4 mg/kg IV initial loading dose followed by subsequent once weekly doses of 2 mg/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.
Measure Participants	242	237
Number (95% Confidence Interval) [percentage of participants]	74.8 30.9%	77.6 32.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neratinib + Paclitaxel, Trastuzumab + Paclitaxel
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5219
	Comments
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.028
	Confidence Interval	(2-Sided) 95%; -0.048 to 0.105
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Duration of Response
Description	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.
Time Frame	From first response to first PD or death, assessed up to 5.3 years after first subject randomized

Outcome Measure Data

Analysis Population Description

patients who responded

Arm/Group Title	Neratinib + Paclitaxel	Trastuzumab + Paclitaxel
Arm/Group Description	Neratinib + Paclitaxel 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. 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.	Trastuzumab + Paclitaxel Trastuzumab: Trastuzumab - 4 mg/kg IV initial loading dose followed by subsequent once weekly doses of 2 mg/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.
Measure Participants	181	184
Median (95% Confidence Interval) [months]	13.1	12.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neratinib + Paclitaxel, Trastuzumab + Paclitaxel
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8431
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.974
	Confidence Interval	(2-Sided) 95%; 0.752 to 1.262
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Clinical Benefit Rate
Description	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.
Time Frame	From randomization to disease progression or death, assessed up to 5.3 years

Outcome Measure Data

Analysis Population Description

all randomized patients

Arm/Group Title	Neratinib + Paclitaxel	Trastuzumab + Paclitaxel
Arm/Group Description	Neratinib + Paclitaxel 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. 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.	Trastuzumab + Paclitaxel Trastuzumab: Trastuzumab - 4 mg/kg IV initial loading dose followed by subsequent once weekly doses of 2 mg/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.
Measure Participants	242	237
Number (95% Confidence Interval) [percentage of participants]	88.4 36.5%	85.2 35.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neratinib + Paclitaxel, Trastuzumab + Paclitaxel
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2360
	Comments
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.032
	Confidence Interval	(2-Sided) 95%; -0.093 to 0.029
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Symptomatic or Progressive Central Nervous System (CNS) Lesions
Description	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.
Time Frame	From randomization to disease progression PD or last tumor assessment, assessed up to 5.3 years

Outcome Measure Data

Analysis Population Description

all randomized patients

Arm/Group Title	Neratinib + Paclitaxel	Trastuzumab + Paclitaxel
Arm/Group Description	Neratinib + Paclitaxel 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. 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.	Trastuzumab + Paclitaxel Trastuzumab: Trastuzumab - 4 mg/kg IV initial loading dose followed by subsequent once weekly doses of 2 mg/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.
Measure Participants	242	237
Count of Participants [Participants]	20 8.3%	41 17.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neratinib + Paclitaxel, Trastuzumab + Paclitaxel
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0036
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.449
	Confidence Interval	(2-Sided) 95%; 0.259 to 0.780
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From First Dose through 28 days after last dose, assessed up to 5.3 years
Arm/Group Title	Neratinib+Paclitaxel		Trastuzumab+Paclitaxel
Arm/Group Description	Neratinib + Paclitaxel		Trastuzumab + Paclitaxel
All Cause Mortality
	Neratinib+Paclitaxel		Trastuzumab+Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Neratinib+Paclitaxel		Trastuzumab+Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	67/240 (27.9%)		56/234 (23.9%)
Blood and lymphatic system disorders
Anaemia	0/240 (0%)		1/234 (0.4%)
Febrile neutropenia	1/240 (0.4%)		0/234 (0%)
Leukopenia	2/240 (0.8%)		0/234 (0%)
Neutropenia	1/240 (0.4%)		0/234 (0%)
Thrombocytopenia	0/240 (0%)		1/234 (0.4%)
Cardiac disorders
Atrial fibrillation	0/240 (0%)		1/234 (0.4%)
Cardiac failure congestive	2/240 (0.8%)		0/234 (0%)
Cardiac tamponade	1/240 (0.4%)		0/234 (0%)
Cardio-respiratory arrest	1/240 (0.4%)		0/234 (0%)
Left ventricular dysfunction	0/240 (0%)		1/234 (0.4%)
Myocardial infarction	1/240 (0.4%)		0/234 (0%)
Pericardial effusion	1/240 (0.4%)		0/234 (0%)
Eye disorders
Retinal degeneration	1/240 (0.4%)		0/234 (0%)
Uveitis	1/240 (0.4%)		0/234 (0%)
Gastrointestinal disorders
Abdominal pain	2/240 (0.8%)		1/234 (0.4%)
Abdominal pain upper	1/240 (0.4%)		0/234 (0%)
Ascites	2/240 (0.8%)		0/234 (0%)
Dental caries	0/240 (0%)		1/234 (0.4%)
Diarrhoea	12/240 (5%)		3/234 (1.3%)
Gastrointestinal haemorrhage	2/240 (0.8%)		0/234 (0%)
Ileus	0/240 (0%)		1/234 (0.4%)
Intestinal obstruction	1/240 (0.4%)		0/234 (0%)
Nausea	2/240 (0.8%)		1/234 (0.4%)
Rectal haemorrhage	1/240 (0.4%)		0/234 (0%)
Small intestinal obstruction	1/240 (0.4%)		0/234 (0%)
Volvulus	1/240 (0.4%)		0/234 (0%)
Vomiting	7/240 (2.9%)		1/234 (0.4%)
General disorders
Adhesion	1/240 (0.4%)		0/234 (0%)
Disease progression	3/240 (1.3%)		0/234 (0%)
Fatigue	1/240 (0.4%)		1/234 (0.4%)
Generalised oedema	1/240 (0.4%)		0/234 (0%)
Multi-organ failure	0/240 (0%)		1/234 (0.4%)
Oedema peripheral	1/240 (0.4%)		1/234 (0.4%)
Pyrexia	3/240 (1.3%)		5/234 (2.1%)
Sudden death	0/240 (0%)		1/234 (0.4%)
Swelling	0/240 (0%)		1/234 (0.4%)
Hepatobiliary disorders
Biliary colic	1/240 (0.4%)		0/234 (0%)
Cholelithiasis	0/240 (0%)		1/234 (0.4%)
Hepatic failure	2/240 (0.8%)		1/234 (0.4%)
Hepatitis	0/240 (0%)		1/234 (0.4%)
Hyperbilirubinaemia	0/240 (0%)		1/234 (0.4%)
Immune system disorders
Contrast media allergy	0/240 (0%)		1/234 (0.4%)
Drug hypersensitivity	1/240 (0.4%)		1/234 (0.4%)
Food allergy	1/240 (0.4%)		0/234 (0%)
Type IV hypersensitivity reaction	1/240 (0.4%)		0/234 (0%)
Infections and infestations
Appendicitis	0/240 (0%)		1/234 (0.4%)
Candida infection	1/240 (0.4%)		0/234 (0%)
Catheter site cellulitis	0/240 (0%)		1/234 (0.4%)
Cellulitis	0/240 (0%)		6/234 (2.6%)
Dengue fever	0/240 (0%)		1/234 (0.4%)
Device related infection	2/240 (0.8%)		2/234 (0.9%)
Empyema	1/240 (0.4%)		0/234 (0%)
Furuncle	1/240 (0.4%)		0/234 (0%)
Gastroenteritis	3/240 (1.3%)		0/234 (0%)
Herpes zoster	0/240 (0%)		1/234 (0.4%)
Infection	1/240 (0.4%)		0/234 (0%)
Lower respiratory tract infection	1/240 (0.4%)		1/234 (0.4%)
Pharyngitis	0/240 (0%)		1/234 (0.4%)
Pleural infection	0/240 (0%)		1/234 (0.4%)
Pneumonia	1/240 (0.4%)		0/234 (0%)
Pulmonary tuberculosis	0/240 (0%)		1/234 (0.4%)
Pyelonephritis acute	0/240 (0%)		1/234 (0.4%)
Rash pustular	1/240 (0.4%)		0/234 (0%)
Respiratory tract infection	0/240 (0%)		1/234 (0.4%)
Septic shock	1/240 (0.4%)		0/234 (0%)
Sinusitis	0/240 (0%)		1/234 (0.4%)
Staphylococcal infection	1/240 (0.4%)		0/234 (0%)
Tooth abscess	0/240 (0%)		1/234 (0.4%)
Upper respiratory tract infection	2/240 (0.8%)		1/234 (0.4%)
Urinary tract infection	0/240 (0%)		1/234 (0.4%)
Injury, poisoning and procedural complications
Accidental overdose	2/240 (0.8%)		3/234 (1.3%)
Ankle fracture	1/240 (0.4%)		0/234 (0%)
Drug administration error	0/240 (0%)		1/234 (0.4%)
Femur fracture	1/240 (0.4%)		0/234 (0%)
Intentional overdose	1/240 (0.4%)		0/234 (0%)
Ligament sprain	0/240 (0%)		1/234 (0.4%)
Lower limb fracture	1/240 (0.4%)		0/234 (0%)
Overdose	2/240 (0.8%)		0/234 (0%)
Pneumothorax traumatic	0/240 (0%)		1/234 (0.4%)
Procedural hypotension	1/240 (0.4%)		0/234 (0%)
Investigations
Activated partial thromboplastin time prolonged	1/240 (0.4%)		0/234 (0%)
Alanine aminotransferase increased	1/240 (0.4%)		1/234 (0.4%)
Aspartate aminotransferase increased	1/240 (0.4%)		1/234 (0.4%)
General physical condition abnormal	1/240 (0.4%)		0/234 (0%)
Weight decreased	1/240 (0.4%)		0/234 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/240 (0.4%)		2/234 (0.9%)
Dehydration	7/240 (2.9%)		1/234 (0.4%)
Hyperglycaemia	0/240 (0%)		1/234 (0.4%)
Hypokalaemia	3/240 (1.3%)		0/234 (0%)
Hyponatraemia	2/240 (0.8%)		0/234 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/240 (0%)		1/234 (0.4%)
Musculoskeletal chest pain	1/240 (0.4%)		1/234 (0.4%)
Pain in extremity	0/240 (0%)		1/234 (0.4%)
Rheumatoid arthritis	1/240 (0.4%)		0/234 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign ovarian tumour	1/240 (0.4%)		0/234 (0%)
Cancer pain	0/240 (0%)		1/234 (0.4%)
Gastric cancer	1/240 (0.4%)		0/234 (0%)
Metastases to central nervous system	2/240 (0.8%)		5/234 (2.1%)
Metastases to meninges	0/240 (0%)		1/234 (0.4%)
Ovarian epithelial cancer	0/240 (0%)		1/234 (0.4%)
Ureteric cancer	0/240 (0%)		1/234 (0.4%)
Nervous system disorders
Brain oedema	1/240 (0.4%)		0/234 (0%)
Cerebellar ischaemia	0/240 (0%)		1/234 (0.4%)
Coma	1/240 (0.4%)		0/234 (0%)
Headache	1/240 (0.4%)		0/234 (0%)
Transient ischaemic attack	1/240 (0.4%)		0/234 (0%)
Psychiatric disorders
Confusional state	4/240 (1.7%)		0/234 (0%)
Depression	0/240 (0%)		1/234 (0.4%)
Schizophrenia	0/240 (0%)		1/234 (0.4%)
Renal and urinary disorders
Prerenal failure	1/240 (0.4%)		0/234 (0%)
Renal failure acute	1/240 (0.4%)		0/234 (0%)
Reproductive system and breast disorders
Menorrhagia	1/240 (0.4%)		0/234 (0%)
Uterine polyp	0/240 (0%)		1/234 (0.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/240 (0.4%)		2/234 (0.9%)
Pleural effusion	1/240 (0.4%)		2/234 (0.9%)
Pneumonia aspiration	0/240 (0%)		1/234 (0.4%)
Pneumonitis	0/240 (0%)		2/234 (0.9%)
Pneumothorax	1/240 (0.4%)		0/234 (0%)
Pulmonary embolism	2/240 (0.8%)		0/234 (0%)
Respiratory failure	0/240 (0%)		1/234 (0.4%)
Skin and subcutaneous tissue disorders
Erythema	0/240 (0%)		1/234 (0.4%)
Vascular disorders
Deep vein thrombosis	0/240 (0%)		1/234 (0.4%)
Hypertension	0/240 (0%)		1/234 (0.4%)
Hypotension	1/240 (0.4%)		0/234 (0%)
Shock	1/240 (0.4%)		0/234 (0%)
Other (Not Including Serious) Adverse Events
	Neratinib+Paclitaxel		Trastuzumab+Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	239/240 (99.6%)		230/234 (98.3%)
Blood and lymphatic system disorders
Anaemia	75/240 (31.3%)		65/234 (27.8%)
Leukopenia	72/240 (30%)		74/234 (31.6%)
Lymphopenia	32/240 (13.3%)		30/234 (12.8%)
Neutropenia	77/240 (32.1%)		79/234 (33.8%)
Gastrointestinal disorders
Abdominal distension	16/240 (6.7%)		4/234 (1.7%)
Abdominal pain	51/240 (21.3%)		26/234 (11.1%)
Abdominal pain upper	30/240 (12.5%)		18/234 (7.7%)
Constipation	35/240 (14.6%)		44/234 (18.8%)
Diarrhoea	222/240 (92.5%)		78/234 (33.3%)
Dyspepsia	31/240 (12.9%)		20/234 (8.5%)
Haemorrhoids	4/240 (1.7%)		12/234 (5.1%)
Nausea	107/240 (44.6%)		70/234 (29.9%)
Stomatitis	59/240 (24.6%)		46/234 (19.7%)
Vomiting	87/240 (36.3%)		37/234 (15.8%)
General disorders
Asthenia	53/240 (22.1%)		36/234 (15.4%)
Fatigue	77/240 (32.1%)		64/234 (27.4%)
Influenza like illness	10/240 (4.2%)		14/234 (6%)
Oedema	11/240 (4.6%)		15/234 (6.4%)
Oedema peripheral	34/240 (14.2%)		40/234 (17.1%)
Pain	13/240 (5.4%)		13/234 (5.6%)
Pyrexia	41/240 (17.1%)		44/234 (18.8%)
Infections and infestations
Cystitis	13/240 (5.4%)		12/234 (5.1%)
Influenza	11/240 (4.6%)		13/234 (5.6%)
Nasopharyngitis	29/240 (12.1%)		33/234 (14.1%)
Paronychia	16/240 (6.7%)		9/234 (3.8%)
Rhinitis	2/240 (0.8%)		12/234 (5.1%)
Upper respiratory tract infection	26/240 (10.8%)		32/234 (13.7%)
Urinary tract infection	17/240 (7.1%)		15/234 (6.4%)
Investigations
Alanine aminotransferase increased	31/240 (12.9%)		26/234 (11.1%)
Aspartate aminotransferase increased	26/240 (10.8%)		22/234 (9.4%)
Blood alkaline phosphatase increased	15/240 (6.3%)		11/234 (4.7%)
Weight decreased	38/240 (15.8%)		12/234 (5.1%)
Weight increased	8/240 (3.3%)		14/234 (6%)
Metabolism and nutrition disorders
Decreased appetite	76/240 (31.7%)		41/234 (17.5%)
Dehydration	18/240 (7.5%)		3/234 (1.3%)
Hypercreatininaemia	13/240 (5.4%)		2/234 (0.9%)
Hyperglycaemia	9/240 (3.8%)		16/234 (6.8%)
Hypocalcaemia	19/240 (7.9%)		4/234 (1.7%)
Hypokalaemia	23/240 (9.6%)		9/234 (3.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	34/240 (14.2%)		44/234 (18.8%)
Back pain	37/240 (15.4%)		27/234 (11.5%)
Bone pain	11/240 (4.6%)		12/234 (5.1%)
Muscle spasms	17/240 (7.1%)		12/234 (5.1%)
Musculoskeletal chest pain	13/240 (5.4%)		5/234 (2.1%)
Musculoskeletal pain	13/240 (5.4%)		18/234 (7.7%)
Myalgia	31/240 (12.9%)		32/234 (13.7%)
Pain in extremity	30/240 (12.5%)		25/234 (10.7%)
Nervous system disorders
Dizziness	52/240 (21.7%)		30/234 (12.8%)
Dysgeusia	35/240 (14.6%)		16/234 (6.8%)
Headache	49/240 (20.4%)		45/234 (19.2%)
Hypoaesthesia	18/240 (7.5%)		25/234 (10.7%)
Neuropathy peripheral	61/240 (25.4%)		60/234 (25.6%)
Paraesthesia	21/240 (8.8%)		12/234 (5.1%)
Peripheral sensory neuropathy	47/240 (19.6%)		53/234 (22.6%)
Psychiatric disorders
Insomnia	32/240 (13.3%)		28/234 (12%)
Reproductive system and breast disorders
Breast pain	5/240 (2.1%)		12/234 (5.1%)
Respiratory, thoracic and mediastinal disorders
Cough	24/240 (10%)		47/234 (20.1%)
Dyspnoea	28/240 (11.7%)		22/234 (9.4%)
Epistaxis	36/240 (15%)		20/234 (8.5%)
Oropharyngeal pain	18/240 (7.5%)		20/234 (8.5%)
Rhinorrhoea	6/240 (2.5%)		17/234 (7.3%)
Skin and subcutaneous tissue disorders
Alopecia	126/240 (52.5%)		133/234 (56.8%)
Dry skin	14/240 (5.8%)		12/234 (5.1%)
Erythema	9/240 (3.8%)		16/234 (6.8%)
Nail disorder	33/240 (13.8%)		31/234 (13.2%)
Palmar-plantar erythrodysaesthesia syndrome	14/240 (5.8%)		7/234 (3%)
Pruritus	19/240 (7.9%)		22/234 (9.4%)
Rash	72/240 (30%)		51/234 (21.8%)
Vascular disorders
Hot flush	13/240 (5.4%)		8/234 (3.4%)
Hypertension	13/240 (5.4%)		19/234 (8.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.