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Study Evaluating The Effects Of Neratinib After Adjuvant Trastuzumab In Women With Early Stage Breast Cancer (ExteNET)

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ClinicalTrials.gov Identifier: NCT00878709
Recruitment Status : Active, not recruiting
First Posted : April 9, 2009
Results First Posted : October 9, 2017
Last Update Posted : August 7, 2018
Sponsor:
Information provided by (Responsible Party):
Puma Biotechnology, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Breast Cancer
Interventions Drug: neratinib
Other: placebo
Enrollment 2840
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Neratinib Placebo
Hide Arm/Group Description Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred. Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year.Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
Period Title: Overall Study
Started 1420 1420
Completed 1095 1183
Not Completed 325 237
Reason Not Completed
Withdrawal by Subject             197             120
Lost to Follow-up             35             33
Other Reasons             93             84
Arm/Group Title Neratinib Placebo Total
Hide Arm/Group Description Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred. Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred. Total of all reporting groups
Overall Number of Baseline Participants 1420 1420 2840
Hide Baseline Analysis Population Description
Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1420 participants 1420 participants 2840 participants
52.3  (10.08) 52.3  (10.28) 52.3  (10.18)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1420 participants 1420 participants 2840 participants
Female
1420
 100.0%
1420
 100.0%
2840
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1420 participants 1420 participants 2840 participants
Asian
188
  13.2%
197
  13.9%
385
  13.6%
Black or African American
27
   1.9%
47
   3.3%
74
   2.6%
White
1165
  82.0%
1135
  79.9%
2300
  81.0%
Other
40
   2.8%
41
   2.9%
81
   2.9%
1.Primary Outcome
Title Invasive Disease-free Survival (iDFS) in Neratinib Arm Compared to Placebo Arm
Hide Description Invasive disease-free survival time is defined as the time from date of randomization until the first disease recurrence of the following events: invasive ipsilateral breast tumor recurrence, invasive contralateral breast cancer, local/regional invasive recurrence, distant recurrence and death from any cause.
Time Frame From randomization until time of event up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.
Arm/Group Title Neratinib Placebo
Hide Arm/Group Description:
Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
Overall Number of Participants Analyzed 1420 1420
Measure Type: Number
Unit of Measure: percentage of participants with events
4.7 7.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Neratinib, Placebo
Comments Invasive disease-free survival (iDFS) in neratinib arm compared to placebo arm.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Log Rank
Comments The Log-rank test is stratified by prior trastuzumab (concurrent or sequential), nodal status (<= 3 or >= 4) and ER/PgR status (positive or negative).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.49 to 0.90
Estimation Comments The hazard ratio is estimated by stratified Cox model. The Cox model is stratified by prior trastuzumab (concurrent or sequential), nodal status (<= 3 or >= 4) and ER/PgR status (positive or negative).
2.Primary Outcome
Title Kaplan-Meier Estimates of Invasive Disease-free Survival (iDFS) at Year 2 by Treatment Arms
Hide Description [Not Specified]
Time Frame From randomization until time of event up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.
Arm/Group Title Neratinib Placebo
Hide Arm/Group Description:
Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
Overall Number of Participants Analyzed 1420 1420
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
94.2
(92.6 to 95.4)
91.9
(90.2 to 93.2)
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival is defined as the time from randomization to death from any cause
Time Frame From time of randomization to death
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Disease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) in Neratinib Arm Compared to Placebo Arm
Hide Description Disease-free survival including DCIS time is defined as the time from date of randomization until the first occurrence of DCIS or an iDFS event (an iDFS event including invasive ipsilateral breast tumor recurrence, invasive contralateral breast cancer, local/regional invasive recurrence, or distant recurrence and death from any.
Time Frame From randomization until time of event up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.
Arm/Group Title Neratinib Placebo
Hide Arm/Group Description:
Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
Overall Number of Participants Analyzed 1420 1420
Measure Type: Number
Unit of Measure: percentage of participants with events
4.7 8.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Neratinib, Placebo
Comments Disease-free survival including ductal carcinoma in situ (DFS-DCIS) in neratinib arm compared to placebo arm.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.45 to 0.83
Estimation Comments The hazard ratio is estimated by stratified Cox model. The Cox model is stratified by prior trastuzumab (concurrent or sequential), nodal status (<= 3 or >= 4) and ER/PgR status (positive or negative).
5.Secondary Outcome
Title Kaplan-Meier Estimates of Disease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) at Year 2 by Treatment Arms
Hide Description [Not Specified]
Time Frame From randomization until time of event up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.
Arm/Group Title Neratinib Placebo
Hide Arm/Group Description:
Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
Overall Number of Participants Analyzed 1420 1420
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
94.2
(92.6 to 95.4)
91.3
(89.6 to 92.7)
6.Secondary Outcome
Title Distant Disease-free Survival (DDFS) in Neratinib Arm Compared to Placebo Arm
Hide Description Distant disease-free survival time is defined as the time from date of randomization until the first occurrence of distant recurrence or death from any cause.
Time Frame From randomization until time of event up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.
Arm/Group Title Neratinib Placebo
Hide Arm/Group Description:
Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
Overall Number of Participants Analyzed 1420 1420
Measure Type: Number
Unit of Measure: percentage of participants with events
3.8 5.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Neratinib, Placebo
Comments Distant disease free survival (DDFS) in neratinib arm compared to placebo arm.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.52 to 1.05
Estimation Comments The hazard ratio is estimated by stratified Cox model. The Cox model is stratified by prior trastuzumab (concurrent or sequential), nodal status (<= 3 or >= 4) and ER/PgR status (positive or negative).
7.Secondary Outcome
Title Kaplan-Meier Estimates of Distant Disease-free Survival (DDFS) at Year 2 by Treatment Arms
Hide Description [Not Specified]
Time Frame From randomization until time of event up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.
Arm/Group Title Neratinib Placebo
Hide Arm/Group Description:
Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
Overall Number of Participants Analyzed 1420 1420
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
95.3
(93.9 to 96.4)
94.0
(92.6 to 95.2)
8.Secondary Outcome
Title Time to Distant Recurrence (TTDR) in Neratinib Arm Compared to Placebo Arm
Hide Description Time to distant recurrence is defined as the time from date of randomization until the first occurrence of distant recurrence or death from breast cancer.
Time Frame From randomization until time of event up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.
Arm/Group Title Neratinib Placebo
Hide Arm/Group Description:
Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
Overall Number of Participants Analyzed 1420 1420
Measure Type: Number
Unit of Measure: percentage of participants with events
3.7 5.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Neratinib, Placebo
Comments Time to distant recurrence (TTDR) in neratinib arm compared to placebo arm.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.51 to 1.04
Estimation Comments The hazard ratio is estimated by stratified Cox model. The Cox model is stratified by prior trastuzumab (concurrent or sequential), nodal status (<= 3 or >= 4) and ER/PgR status (positive or negative).
9.Secondary Outcome
Title Kaplan-Meier Estimates of Time to Distant Recurrence (TTDR) Survival at Year 2 by Treatment Arms
Hide Description [Not Specified]
Time Frame From randomization until time of event up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.
Arm/Group Title Neratinib Placebo
Hide Arm/Group Description:
Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
Overall Number of Participants Analyzed 1420 1420
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
95.5
(94.1 to 96.6)
94.2
(92.8 to 95.3)
10.Secondary Outcome
Title Central Nervous System Recurrence in Neratinib Arm Compared to Placebo Arm
Hide Description CNS recurrence is defined as the time from randomization to CNS as the first distant recurrence. Competing events include distant recurrence at other sites as the first distant recurrence and death from any cause prior to distant recurrence.
Time Frame From randomization until time of event up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.
Arm/Group Title Neratinib Placebo
Hide Arm/Group Description:
Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
Overall Number of Participants Analyzed 1420 1420
Measure Type: Number
Unit of Measure: percentage of participants with events
0.8 1.1
11.Secondary Outcome
Title Cumulative Incidence of Central Nervous System Recurrence (CNS) at Year 2
Hide Description Cumulative incidence of Central Nervous System Recurrence (CNS) is estimated by Gray’s method (Gray,1988).
Time Frame From randomization until time of event up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.
Arm/Group Title Neratinib Placebo
Hide Arm/Group Description:
Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
Overall Number of Participants Analyzed 1420 1420
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.92
(0.49 to 1.59)
1.16
(0.68 to 1.87)
Time Frame From first dose through 28 days after the last dose, up to two years.
Adverse Event Reporting Description The safety population included all participants who received at least one dose of investigational product.
 
Arm/Group Title Neratinib Placebo
Hide Arm/Group Description Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred. Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
All-Cause Mortality
Neratinib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Neratinib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   103/1408 (7.32%)   85/1408 (6.04%) 
Blood and lymphatic system disorders     
Anaemia  1  1/1408 (0.07%)  1/1408 (0.07%) 
Cardiac disorders     
Angina pectoris  1  1/1408 (0.07%)  0/1408 (0.00%) 
Myocardial infarction  1  1/1408 (0.07%)  1/1408 (0.07%) 
Atrial fibrillation  1  0/1408 (0.00%)  1/1408 (0.07%) 
Sinus tachycardia  1  0/1408 (0.00%)  1/1408 (0.07%) 
Tachycardia  1  0/1408 (0.00%)  1/1408 (0.07%) 
Ear and labyrinth disorders     
Vertigo  1  0/1408 (0.00%)  1/1408 (0.07%) 
Gastrointestinal disorders     
Diarrhoea  1  22/1408 (1.56%)  1/1408 (0.07%) 
Vomiting  1  12/1408 (0.85%)  1/1408 (0.07%) 
Nausea  1  4/1408 (0.28%)  1/1408 (0.07%) 
Abdominal pain  1  2/1408 (0.14%)  0/1408 (0.00%) 
Pancreatitis  1  2/1408 (0.14%)  1/1408 (0.07%) 
Abdominal pain upper  1  1/1408 (0.07%)  0/1408 (0.00%) 
Abdominal strangulated hernia  1  1/1408 (0.07%)  0/1408 (0.00%) 
Enterocele  1  1/1408 (0.07%)  0/1408 (0.00%) 
Periodontal disease  1  1/1408 (0.07%)  0/1408 (0.00%) 
Rectal cancer  1  1/1408 (0.07%)  0/1408 (0.00%) 
Abdominal distension  1  0/1408 (0.00%)  1/1408 (0.07%) 
Colitis  1  0/1408 (0.00%)  2/1408 (0.14%) 
Colitis ischaemic  1  0/1408 (0.00%)  1/1408 (0.07%) 
Constipation  1  0/1408 (0.00%)  1/1408 (0.07%) 
General disorders     
Fatigue  1  3/1408 (0.21%)  0/1408 (0.00%) 
Non-cardiac chest pain  1  3/1408 (0.21%)  0/1408 (0.00%) 
Pyrexia  1  2/1408 (0.14%)  1/1408 (0.07%) 
Asthenia  1  1/1408 (0.07%)  0/1408 (0.00%) 
Hepatobiliary disorders     
Cholelithiasis  1  2/1408 (0.14%)  0/1408 (0.00%) 
Cholecystitis  1  1/1408 (0.07%)  0/1408 (0.00%) 
Cholecystitis acute  1  1/1408 (0.07%)  0/1408 (0.00%) 
Hepatic function abnormal  1  0/1408 (0.00%)  1/1408 (0.07%) 
Hypertransaminasaemia  1  0/1408 (0.00%)  1/1408 (0.07%) 
Jaundice cholestatic  1  0/1408 (0.00%)  1/1408 (0.07%) 
Immune system disorders     
Food allergy  1  0/1408 (0.00%)  1/1408 (0.07%) 
Infections and infestations     
Cellulitis  1  6/1408 (0.43%)  4/1408 (0.28%) 
Erysipelas  1  5/1408 (0.36%)  0/1408 (0.00%) 
Bronchitis  1  2/1408 (0.14%)  1/1408 (0.07%) 
Anal abscess  1  1/1408 (0.07%)  0/1408 (0.00%) 
Anorectal cellulitis  1  1/1408 (0.07%)  0/1408 (0.00%) 
Appendicitis  1  1/1408 (0.07%)  1/1408 (0.07%) 
Appendicitis perforated  1  1/1408 (0.07%)  0/1408 (0.00%) 
Breast cellulitis  1  1/1408 (0.07%)  1/1408 (0.07%) 
Cystitis  1  1/1408 (0.07%)  0/1408 (0.00%) 
Escherichia urinary tract infection  1  1/1408 (0.07%)  0/1408 (0.00%) 
Gastroenteritis  1  1/1408 (0.07%)  0/1408 (0.00%) 
Gastroenteritis salmonella  1  1/1408 (0.07%)  0/1408 (0.00%) 
Gastrointestinal viral infection  1  1/1408 (0.07%)  0/1408 (0.00%) 
Herpes zoster  1  1/1408 (0.07%)  0/1408 (0.00%) 
Localised infection  1  1/1408 (0.07%)  0/1408 (0.00%) 
Ophthalmic herpes zoster  1  1/1408 (0.07%)  0/1408 (0.00%) 
Pneumonia  1  1/1408 (0.07%)  4/1408 (0.28%) 
Rectal abscess  1  1/1408 (0.07%)  0/1408 (0.00%) 
Streptococcal sepsis  1  1/1408 (0.07%)  0/1408 (0.00%) 
Viral infection  1  1/1408 (0.07%)  0/1408 (0.00%) 
Abdominal wall abscess  1  0/1408 (0.00%)  1/1408 (0.07%) 
Breast abscess  1  0/1408 (0.00%)  1/1408 (0.07%) 
Device related infection  1  0/1408 (0.00%)  3/1408 (0.21%) 
Diverticulitis  1  0/1408 (0.00%)  1/1408 (0.07%) 
Incision site cellulitis  1  0/1408 (0.00%)  1/1408 (0.07%) 
Mastitis  1  0/1408 (0.00%)  1/1408 (0.07%) 
Septic shock  1  0/1408 (0.00%)  1/1408 (0.07%) 
Injury, poisoning and procedural complications     
Ankle fracture  1  1/1408 (0.07%)  0/1408 (0.00%) 
Fracture  1  1/1408 (0.07%)  0/1408 (0.00%) 
Multiple injuries  1  1/1408 (0.07%)  0/1408 (0.00%) 
Sternal fracture  1  1/1408 (0.07%)  0/1408 (0.00%) 
Wound dehiscence  1  1/1408 (0.07%)  1/1408 (0.07%) 
Wrist fracture  1  1/1408 (0.07%)  0/1408 (0.00%) 
Fall  1  0/1408 (0.00%)  1/1408 (0.07%) 
Hip fracture  1  0/1408 (0.00%)  1/1408 (0.07%) 
Humerus fracture  1  0/1408 (0.00%)  1/1408 (0.07%) 
Meniscus injury  1  0/1408 (0.00%)  2/1408 (0.14%) 
Patella fracture  1  0/1408 (0.00%)  1/1408 (0.07%) 
Investigations     
Alanine aminotransferase increased  1  4/1408 (0.28%)  0/1408 (0.00%) 
Aspartate aminotransferase increased  1  4/1408 (0.28%)  0/1408 (0.00%) 
Blood creatine increased  1  1/1408 (0.07%)  0/1408 (0.00%) 
Blood thyroid stimulating hormone increased  1  1/1408 (0.07%)  0/1408 (0.00%) 
Electrocardiogram T wave inversion  1  1/1408 (0.07%)  0/1408 (0.00%) 
Staphylococcus test positive  1  1/1408 (0.07%)  0/1408 (0.00%) 
Ejection fraction decreased  1  0/1408 (0.00%)  1/1408 (0.07%) 
Metabolism and nutrition disorders     
Dehydration  1  9/1408 (0.64%)  1/1408 (0.07%) 
Hypokalaemia  1  1/1408 (0.07%)  0/1408 (0.00%) 
Hypomagnesaemia  1  1/1408 (0.07%)  0/1408 (0.00%) 
Hyponatraemia  1  1/1408 (0.07%)  1/1408 (0.07%) 
Electrolyte imbalance  1  0/1408 (0.00%)  1/1408 (0.07%) 
Hypoglycaemia  1  0/1408 (0.00%)  1/1408 (0.07%) 
Musculoskeletal and connective tissue disorders     
Osteoarthritis  1  1/1408 (0.07%)  1/1408 (0.07%) 
Lumbar spinal stenosis  1  0/1408 (0.00%)  1/1408 (0.07%) 
Muscle spasms  1  0/1408 (0.00%)  1/1408 (0.07%) 
Muscular weakness  1  0/1408 (0.00%)  1/1408 (0.07%) 
Musculoskeletal chest pain  1  0/1408 (0.00%)  1/1408 (0.07%) 
Pain in extremity  1  0/1408 (0.00%)  1/1408 (0.07%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  2/1408 (0.14%)  2/1408 (0.14%) 
Acute myeloid leukaemia  1  1/1408 (0.07%)  0/1408 (0.00%) 
Benign female reproductive tract neoplasm  1  1/1408 (0.07%)  0/1408 (0.00%) 
Breast cancer metastatic  1  1/1408 (0.07%)  0/1408 (0.00%) 
Cancer pain  1  1/1408 (0.07%)  0/1408 (0.00%) 
Glioblastoma  1  1/1408 (0.07%)  0/1408 (0.00%) 
Glioma  1  1/1408 (0.07%)  0/1408 (0.00%) 
Malignant melanoma  1  1/1408 (0.07%)  0/1408 (0.00%) 
Malignant melanoma in situ  1  1/1408 (0.07%)  0/1408 (0.00%) 
Malignant pleural effusion  1  1/1408 (0.07%)  0/1408 (0.00%) 
Metastases to meninges  1  1/1408 (0.07%)  0/1408 (0.00%) 
Benign breast neoplasm  1  0/1408 (0.00%)  1/1408 (0.07%) 
Breast cancer  1  0/1408 (0.00%)  2/1408 (0.14%) 
Breast neoplasm  1  0/1408 (0.00%)  1/1408 (0.07%) 
Gastric cancer  1  0/1408 (0.00%)  1/1408 (0.07%) 
Lung adenocarcinoma  1  0/1408 (0.00%)  1/1408 (0.07%) 
Metastases to eye  1  0/1408 (0.00%)  1/1408 (0.07%) 
Sarcoma  1  0/1408 (0.00%)  1/1408 (0.07%) 
Sarcoma uterus  1  0/1408 (0.00%)  1/1408 (0.07%) 
Uterine leiomyoma  1  0/1408 (0.00%)  1/1408 (0.07%) 
Vascular neoplasm  1  0/1408 (0.00%)  1/1408 (0.07%) 
Nervous system disorders     
Syncope  1  3/1408 (0.21%)  2/1408 (0.14%) 
Ageusia  1  1/1408 (0.07%)  0/1408 (0.00%) 
Anosmia  1  1/1408 (0.07%)  0/1408 (0.00%) 
Cerebral haemorrhage  1  1/1408 (0.07%)  0/1408 (0.00%) 
Cerebral infarction  1  1/1408 (0.07%)  0/1408 (0.00%) 
Paresis  1  1/1408 (0.07%)  0/1408 (0.00%) 
Brain oedema  1  0/1408 (0.00%)  1/1408 (0.07%) 
Carotid artery stenosis  1  0/1408 (0.00%)  1/1408 (0.07%) 
Cerebrovascular accident  1  0/1408 (0.00%)  1/1408 (0.07%) 
Dizziness  1  0/1408 (0.00%)  1/1408 (0.07%) 
Headache  1  0/1408 (0.00%)  1/1408 (0.07%) 
Intercostal neuralgia  1  0/1408 (0.00%)  1/1408 (0.07%) 
Speech disorder  1  0/1408 (0.00%)  1/1408 (0.07%) 
Transient ischaemic attack  1  0/1408 (0.00%)  1/1408 (0.07%) 
Tremor  1  0/1408 (0.00%)  1/1408 (0.07%) 
Psychiatric disorders     
Mental status changes  1  2/1408 (0.14%)  0/1408 (0.00%) 
Depression  1  1/1408 (0.07%)  2/1408 (0.14%) 
Anxiety  1  0/1408 (0.00%)  1/1408 (0.07%) 
Mental disorder  1  0/1408 (0.00%)  1/1408 (0.07%) 
Renal and urinary disorders     
Renal failure acute  1  3/1408 (0.21%)  0/1408 (0.00%) 
Renal failure  1  2/1408 (0.14%)  0/1408 (0.00%) 
Hyperuricosuria  1  1/1408 (0.07%)  0/1408 (0.00%) 
Renal colic  1  1/1408 (0.07%)  0/1408 (0.00%) 
Bladder prolapse  1  0/1408 (0.00%)  1/1408 (0.07%) 
Reproductive system and breast disorders     
Endometrial hyperplasia  1  1/1408 (0.07%)  1/1408 (0.07%) 
Endometrial hypertrophy  1  1/1408 (0.07%)  0/1408 (0.00%) 
Endometriosis  1  1/1408 (0.07%)  0/1408 (0.00%) 
Metrorrhagia  1  1/1408 (0.07%)  1/1408 (0.07%) 
Ovarian cyst  1  0/1408 (0.00%)  1/1408 (0.07%) 
Uterine polyp  1  0/1408 (0.00%)  1/1408 (0.07%) 
Vulval leukoplakia  1  0/1408 (0.00%)  1/1408 (0.07%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism  1  3/1408 (0.21%)  3/1408 (0.21%) 
Dyspnoea  1  2/1408 (0.14%)  1/1408 (0.07%) 
Atelectasis  1  1/1408 (0.07%)  0/1408 (0.00%) 
Pleural effusion  1  1/1408 (0.07%)  1/1408 (0.07%) 
Pneumothorax  1  1/1408 (0.07%)  1/1408 (0.07%) 
Pneumonitis  1  0/1408 (0.00%)  1/1408 (0.07%) 
Tachypnoea  1  0/1408 (0.00%)  1/1408 (0.07%) 
Skin and subcutaneous tissue disorders     
Dermatitis  1  1/1408 (0.07%)  0/1408 (0.00%) 
Erythema  1  1/1408 (0.07%)  0/1408 (0.00%) 
Skin necrosis  1  1/1408 (0.07%)  1/1408 (0.07%) 
Skin disorder  1  0/1408 (0.00%)  1/1408 (0.07%) 
Surgical and medical procedures     
Hysterosalpingo-oophorectomy  1  0/1408 (0.00%)  1/1408 (0.07%) 
Vascular disorders     
Hypotension  1  1/1408 (0.07%)  0/1408 (0.00%) 
Deep vein thrombosis  1  0/1408 (0.00%)  1/1408 (0.07%) 
Hypertension  1  0/1408 (0.00%)  1/1408 (0.07%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Neratinib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   1386/1408 (98.44%)   1234/1408 (87.64%) 
Gastrointestinal disorders     
Diarrhoea  1  1341/1408 (95.24%)  499/1408 (35.44%) 
Nausea  1  605/1408 (42.97%)  303/1408 (21.52%) 
Vomiting  1  364/1408 (25.85%)  113/1408 (8.03%) 
Abdominal pain  1  339/1408 (24.08%)  144/1408 (10.23%) 
Abdominal pain upper  1  212/1408 (15.06%)  96/1408 (6.82%) 
Dyspepsia  1  139/1408 (9.87%)  59/1408 (4.19%) 
Constipation  1  115/1408 (8.17%)  134/1408 (9.52%) 
Stomatitis  1  85/1408 (6.04%)  29/1408 (2.06%) 
Abdominal distension  1  73/1408 (5.18%)  49/1408 (3.48%) 
General disorders     
Fatigue  1  381/1408 (27.06%)  283/1408 (20.10%) 
Asthenia  1  107/1408 (7.60%)  110/1408 (7.81%) 
Pyrexia  1  77/1408 (5.47%)  54/1408 (3.84%) 
Infections and infestations     
Nasopharyngitis  1  84/1408 (5.97%)  126/1408 (8.95%) 
Urinary tract infection  1  72/1408 (5.11%)  23/1408 (1.63%) 
Investigations     
Alanine aminotransferase increased  1  118/1408 (8.38%)  45/1408 (3.20%) 
Aspartate aminotransferase increased  1  101/1408 (7.17%)  46/1408 (3.27%) 
Electrocardiogram QT prolonged  1  49/1408 (3.48%)  93/1408 (6.61%) 
Metabolism and nutrition disorders     
Decreased appetite  1  170/1408 (12.07%)  40/1408 (2.84%) 
Musculoskeletal and connective tissue disorders     
Muscle spasms  1  159/1408 (11.29%)  44/1408 (3.13%) 
Arthralgia  1  86/1408 (6.11%)  162/1408 (11.51%) 
Back pain  1  79/1408 (5.61%)  134/1408 (9.52%) 
Pain in extremity  1  58/1408 (4.12%)  98/1408 (6.96%) 
Nervous system disorders     
Headache  1  278/1408 (19.74%)  275/1408 (19.53%) 
Dizziness  1  146/1408 (10.37%)  127/1408 (9.02%) 
Psychiatric disorders     
Insomnia  1  44/1408 (3.13%)  73/1408 (5.18%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis  1  71/1408 (5.04%)  18/1408 (1.28%) 
Cough  1  69/1408 (4.90%)  92/1408 (6.53%) 
Skin and subcutaneous tissue disorders     
Rash  1  211/1408 (14.99%)  100/1408 (7.10%) 
Dry skin  1  85/1408 (6.04%)  33/1408 (2.34%) 
Vascular disorders     
Hot flush  1  40/1408 (2.84%)  84/1408 (5.97%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Senior Director, Clinical Operations
Organization: Puma Biotechnology, Inc.
Phone: +1 (424) 248-6500
Responsible Party: Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier: NCT00878709     History of Changes
Other Study ID Numbers: 3144A2-3004 / B1891004
First Submitted: April 8, 2009
First Posted: April 9, 2009
Results First Submitted: August 10, 2017
Results First Posted: October 9, 2017
Last Update Posted: August 7, 2018