ClinicalTrials.gov
ClinicalTrials.gov Menu

Neratinib With and Without Temsirolimus for Patients With HER2 Activating Mutations in Non-Small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01827267
Recruitment Status : Completed
First Posted : April 9, 2013
Results First Posted : September 11, 2017
Last Update Posted : July 3, 2018
Sponsor:
Information provided by (Responsible Party):
Puma Biotechnology, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HER2-mutant Non-Small Cell Lung Cancer
Interventions Drug: neratinib
Drug: temsirolimus
Enrollment 62
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Neratinib Neratinib+Temsirolimus
Hide Arm/Group Description Neratinib 240 mg Neratinib 240 mg + Temsirolimus 15 mg.
Period Title: Overall Study
Started [1] 18 [2] 44 [3]
Received Study Drug 17 43
Crossed Over to Neratinib + Temsirolimus 11 0
Completed [4] 13 32
Not Completed 5 12
Reason Not Completed
Did not receive study drug             1             1
Physician Decision             1             0
Disease Progression             1             1
Sponsor Discontinued Study             2             8
Still on study             0             2
[1]
Number of subjects randomized
[2]
18 subjects were randomized but 17 received treatment.
[3]
44 subjects were randomized; 43 subjects were treated.
[4]
Subjects completed study upon death.
Arm/Group Title Neratinib Neratinib+Temsirolimus Total
Hide Arm/Group Description Neratinib 240 mg Neratinib 240 mg + Temsirolimus 15 mg. Total of all reporting groups
Overall Number of Baseline Participants 17 43 60
Hide Baseline Analysis Population Description
All subjects who received at least one dose of study medication
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants 43 participants 60 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
10
  58.8%
19
  44.2%
29
  48.3%
>=65 years
7
  41.2%
24
  55.8%
31
  51.7%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 17 participants 43 participants 60 participants
62.24  (8.88) 63.44  (12.72) 63.10  (11.70)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants 43 participants 60 participants
Female
9
  52.9%
32
  74.4%
41
  68.3%
Male
8
  47.1%
11
  25.6%
19
  31.7%
1.Primary Outcome
Title Objective Response Rate (ORR)
Hide Description

ORR is defined as proportion of subjects who achieved confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

A complete or partial response must be confirmed no less than 4-weeks after the criteria for response are initially met.

Time Frame From randomization to last tumor assessment, assessed up to 116.5 weeks. For the Neratinib arm, only tumor assessments prior to crossover were included.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least 1 dose of drug
Arm/Group Title Neratinib Neratinib+Temsirolimus
Hide Arm/Group Description:
Neratinib 240 mg
Neratinib 240 mg + Temsirolimus 15 mg.
Overall Number of Participants Analyzed 17 43
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
6
  14.0%
2.Secondary Outcome
Title Clinical Benefit Rate (CBR)
Hide Description CBR is defined as the proportion of patients who achieved objective response (CR or PR) or stable disease (SD) for at least 12 weeks.
Time Frame From randomization to last tumor assessment, assessed up to 116.5 weeks. For the Neratinib arm, only tumor assessments prior to crossover were included.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least one dose.
Arm/Group Title Neratinib Neratinib+Temsirolimus
Hide Arm/Group Description:
Neratinib 240 mg
Neratinib 240 mg + Temsirolimus 15 mg.
Overall Number of Participants Analyzed 17 43
Measure Type: Count of Participants
Unit of Measure: Participants
6
  35.3%
21
  48.8%
3.Secondary Outcome
Title Duration of Response (DOR)
Hide 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, progressive disease (PD), or death was objectively documented, taking as a reference for PD the smallest measurements recorded since enrollment, per RECIST (v1.1) criteria.
Time Frame From randomization to last tumor assessment, assessed up to 116.5 weeks. For the Neratinib arm, only tumor assessments prior to crossover were included.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least 1 dose of drug and had either complete or partial response.
Arm/Group Title Neratinib Neratinib+Temsirolimus
Hide Arm/Group Description:
Neratinib 240 mg
Neratinib 240 mg + Temsirolimus 15 mg.
Overall Number of Participants Analyzed 0 6
Measure Type: Count of Participants
Unit of Measure: Participants
Less than 3 months 0
2
  33.3%
3 to less than 6 months 0
2
  33.3%
6 to less than 12 months 0
0
   0.0%
Greater than 12 months 0
2
  33.3%
4.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description Defined as time from date of randomization until the first disease recurrence or progression per RECIST V1.1 or death due to any cause; censored at the last assessable evaluation or at the initiation of new anti-cancer therapy. Disease assessment is based on investigator tumor assessments. If no post-baseline tumor assessment then censored at enrollment date.
Time Frame From randomization to last tumor assessment, assessed up to 116.5 weeks. For the Neratinib arm, only tumor assessments prior to crossover were included.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least 1 dose of drug
Arm/Group Title Neratinib Neratinib+Temsirolimus
Hide Arm/Group Description:
Neratinib 240 mg
Neratinib 240 mg + Temsirolimus 15 mg.
Overall Number of Participants Analyzed 17 43
Median (95% Confidence Interval)
Unit of Measure: months
2.9
(1.4 to 9.8)
4.0
(2.9 to 5.4)
5.Secondary Outcome
Title Overall Survival (OS)
Hide Description Defined as the time (month) from randomization to death due to any cause; censored at the date last known alive.
Time Frame From randomization to death or end of long term follow-up, assessed up to 31.8 months.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least 1 dose of drug
Arm/Group Title Neratinib Neratinib+Temsirolimus
Hide Arm/Group Description:
Neratinib 240 mg
Neratinib 240 mg + Temsirolimus 15 mg.
Overall Number of Participants Analyzed 17 43
Median (95% Confidence Interval)
Unit of Measure: months
10.0
(4.9 to 18.9)
15.1
(10.8 to 17.7)
Time Frame From time of first dose through 28 days after last dose, assessed up to 116.5 weeks.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Neratinib Neratinib+Temsirolimus Ner+Tem Post Crossover
Hide Arm/Group Description Neratinib 240 mg Neratinib 240 mg + Temsirolimus 15 mg. Neratinib 240 mg + Temsirolimus 15 mg for subjects who crossed over from Neratinb 240 mg arm
All-Cause Mortality
Neratinib Neratinib+Temsirolimus Ner+Tem Post Crossover
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Neratinib Neratinib+Temsirolimus Ner+Tem Post Crossover
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/17 (41.18%)   16/43 (37.21%)   7/11 (63.64%) 
Blood and lymphatic system disorders       
Anaemia  1  0/17 (0.00%)  1/43 (2.33%)  0/11 (0.00%) 
Cardiac disorders       
Cardio-respiratory arrest  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Tachycardia  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Gastrointestinal disorders       
Diarrhoea  1  2/17 (11.76%)  4/43 (9.30%)  0/11 (0.00%) 
Dysphagia  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Nausea  1  1/17 (5.88%)  2/43 (4.65%)  0/11 (0.00%) 
Vomiting  1  0/17 (0.00%)  2/43 (4.65%)  0/11 (0.00%) 
General disorders       
Asthenia  1  0/17 (0.00%)  1/43 (2.33%)  1/11 (9.09%) 
General physical health deterioration  1  0/17 (0.00%)  0/43 (0.00%)  2/11 (18.18%) 
Pyrexia  1  0/17 (0.00%)  2/43 (4.65%)  0/11 (0.00%) 
Immune system disorders       
Anaphylactic shock  1  0/17 (0.00%)  1/43 (2.33%)  0/11 (0.00%) 
Infections and infestations       
Infection  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Parainfluenzae virus infection  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Pneumonia  1  0/17 (0.00%)  2/43 (4.65%)  0/11 (0.00%) 
Pneumonia bacterial  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Upper respiratory tract infection  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Injury, poisoning and procedural complications       
Accidental overdose  1  0/17 (0.00%)  1/43 (2.33%)  0/11 (0.00%) 
Infusion related reaction  1  0/17 (0.00%)  1/43 (2.33%)  0/11 (0.00%) 
Investigations       
Blood uric acid increased  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
General physical condition abnormal  1  1/17 (5.88%)  1/43 (2.33%)  0/11 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite  1  0/17 (0.00%)  1/43 (2.33%)  0/11 (0.00%) 
Dehydration  1  1/17 (5.88%)  1/43 (2.33%)  1/11 (9.09%) 
Hyponatraemia  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Neck pain  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Malignant pleural effusion  1  0/17 (0.00%)  1/43 (2.33%)  0/11 (0.00%) 
Nervous system disorders       
Cerebrovascular accident  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Dizziness  1  0/17 (0.00%)  1/43 (2.33%)  0/11 (0.00%) 
Monoparesis  1  0/17 (0.00%)  1/43 (2.33%)  0/11 (0.00%) 
Nervous system disorder  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Neuropathy peripheral  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Pachymeningitis  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Somnolence  1  0/17 (0.00%)  1/43 (2.33%)  0/11 (0.00%) 
Syncope  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Psychiatric disorders       
Delirium  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Renal and urinary disorders       
Urinary retention  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Reproductive system and breast disorders       
Pelvic pain  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  1  0/17 (0.00%)  3/43 (6.98%)  0/11 (0.00%) 
Lung disorder  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Pleural effusion  1  2/17 (11.76%)  1/43 (2.33%)  2/11 (18.18%) 
Pneumonia aspiration  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Pulmonary embolism  1  0/17 (0.00%)  1/43 (2.33%)  1/11 (9.09%) 
Respiratory distress  1  0/17 (0.00%)  1/43 (2.33%)  0/11 (0.00%) 
Vascular disorders       
Deep vein thrombosis  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Embolism  1  0/17 (0.00%)  1/43 (2.33%)  0/11 (0.00%) 
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 Neratinib+Temsirolimus Ner+Tem Post Crossover
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   17/17 (100.00%)   43/43 (100.00%)   10/11 (90.91%) 
Blood and lymphatic system disorders       
Anaemia  1  5/17 (29.41%)  18/43 (41.86%)  5/11 (45.45%) 
Lymphopenia  1  0/17 (0.00%)  4/43 (9.30%)  0/11 (0.00%) 
Neutropenia  1  0/17 (0.00%)  4/43 (9.30%)  0/11 (0.00%) 
Thrombocytopenia  1  1/17 (5.88%)  2/43 (4.65%)  0/11 (0.00%) 
Thrombocytosis  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Cardiac disorders       
Arrhythmia  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Atrial fibrillation  1  2/17 (11.76%)  0/43 (0.00%)  0/11 (0.00%) 
Left atrial dilatation  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Tachycardia  1  1/17 (5.88%)  1/43 (2.33%)  1/11 (9.09%) 
Eye disorders       
Vision blurred  1  0/17 (0.00%)  3/43 (6.98%)  0/11 (0.00%) 
Gastrointestinal disorders       
Abdominal distension  1  2/17 (11.76%)  2/43 (4.65%)  0/11 (0.00%) 
Abdominal pain  1  6/17 (35.29%)  8/43 (18.60%)  0/11 (0.00%) 
Abdominal pain upper  1  3/17 (17.65%)  2/43 (4.65%)  1/11 (9.09%) 
Aphthous stomatitis  1  0/17 (0.00%)  1/43 (2.33%)  1/11 (9.09%) 
Cheilosis  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Constipation  1  7/17 (41.18%)  18/43 (41.86%)  1/11 (9.09%) 
Diarrhoea  1  13/17 (76.47%)  37/43 (86.05%)  5/11 (45.45%) 
Dry mouth  1  0/17 (0.00%)  3/43 (6.98%)  0/11 (0.00%) 
Dyspepsia  1  2/17 (11.76%)  2/43 (4.65%)  0/11 (0.00%) 
Dysphagia  1  1/17 (5.88%)  4/43 (9.30%)  0/11 (0.00%) 
Flatulence  1  2/17 (11.76%)  3/43 (6.98%)  0/11 (0.00%) 
Gastrointestinal hypermotility  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Gastrooesophageal reflux disease  1  0/17 (0.00%)  2/43 (4.65%)  1/11 (9.09%) 
Haemorrhoids  1  0/17 (0.00%)  1/43 (2.33%)  1/11 (9.09%) 
Mouth haemorrhage  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Nausea  1  7/17 (41.18%)  24/43 (55.81%)  0/11 (0.00%) 
Oesophageal fistula  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Stomatitis  1  1/17 (5.88%)  21/43 (48.84%)  2/11 (18.18%) 
Vomiting  1  5/17 (29.41%)  14/43 (32.56%)  1/11 (9.09%) 
General disorders       
Asthenia  1  6/17 (35.29%)  12/43 (27.91%)  1/11 (9.09%) 
Catheter site erythema  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Catheter site related reaction  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Chest discomfort  1  1/17 (5.88%)  2/43 (4.65%)  0/11 (0.00%) 
Chills  1  3/17 (17.65%)  5/43 (11.63%)  1/11 (9.09%) 
Fatigue  1  4/17 (23.53%)  17/43 (39.53%)  1/11 (9.09%) 
Gait disturbance  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Influenza like illness  1  1/17 (5.88%)  1/43 (2.33%)  0/11 (0.00%) 
Local swelling  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Malaise  1  1/17 (5.88%)  1/43 (2.33%)  1/11 (9.09%) 
Nodule  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Non-cardiac chest pain  1  1/17 (5.88%)  1/43 (2.33%)  0/11 (0.00%) 
Oedema  1  0/17 (0.00%)  1/43 (2.33%)  1/11 (9.09%) 
Oedema peripheral  1  0/17 (0.00%)  7/43 (16.28%)  0/11 (0.00%) 
Pain  1  1/17 (5.88%)  0/43 (0.00%)  1/11 (9.09%) 
Pyrexia  1  1/17 (5.88%)  4/43 (9.30%)  2/11 (18.18%) 
Immune system disorders       
Hypersensitivity  1  0/17 (0.00%)  1/43 (2.33%)  1/11 (9.09%) 
Infections and infestations       
Bronchitis  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Cystitis  1  0/17 (0.00%)  1/43 (2.33%)  1/11 (9.09%) 
Endocarditis  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Escherichia urinary tract infection  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Herpes zoster  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Lung abscess  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Lung infection  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Paronychia  1  1/17 (5.88%)  3/43 (6.98%)  1/11 (9.09%) 
Pneumonia  1  0/17 (0.00%)  2/43 (4.65%)  1/11 (9.09%) 
Pyelonephritis  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Rash pustular  1  0/17 (0.00%)  2/43 (4.65%)  1/11 (9.09%) 
Rhinitis  1  0/17 (0.00%)  4/43 (9.30%)  0/11 (0.00%) 
Sinusitis  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Upper respiratory tract infection  1  0/17 (0.00%)  2/43 (4.65%)  1/11 (9.09%) 
Urinary tract infection  1  2/17 (11.76%)  4/43 (9.30%)  0/11 (0.00%) 
Injury, poisoning and procedural complications       
Fracture  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Investigations       
Activated partial thromboplastin time prolonged  1  0/17 (0.00%)  3/43 (6.98%)  0/11 (0.00%) 
Alanine aminotransferase increased  1  1/17 (5.88%)  10/43 (23.26%)  0/11 (0.00%) 
Amylase increased  1  2/17 (11.76%)  4/43 (9.30%)  0/11 (0.00%) 
Aspartate aminotransferase increased  1  2/17 (11.76%)  10/43 (23.26%)  0/11 (0.00%) 
Blood alkaline phosphatase increased  1  0/17 (0.00%)  1/43 (2.33%)  1/11 (9.09%) 
Blood calcium decreased  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Blood creatine phosphokinase increased  1  1/17 (5.88%)  2/43 (4.65%)  1/11 (9.09%) 
Blood creatinine increased  1  1/17 (5.88%)  4/43 (9.30%)  1/11 (9.09%) 
Blood lactate dehydrogenase increased  1  3/17 (17.65%)  3/43 (6.98%)  0/11 (0.00%) 
Blood phosphorus increased  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Blood triglycerides increased  1  0/17 (0.00%)  3/43 (6.98%)  0/11 (0.00%) 
Electrocardiogram QT prolonged  1  0/17 (0.00%)  1/43 (2.33%)  1/11 (9.09%) 
Gamma-glutamyltransferase increased  1  2/17 (11.76%)  5/43 (11.63%)  1/11 (9.09%) 
International normalised ratio increased  1  1/17 (5.88%)  0/43 (0.00%)  1/11 (9.09%) 
Lymphocyte count decreased  1  0/17 (0.00%)  3/43 (6.98%)  0/11 (0.00%) 
Neutrophil count increased  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Prothrombin time prolonged  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Weight decreased  1  2/17 (11.76%)  10/43 (23.26%)  1/11 (9.09%) 
White blood cell count decreased  1  1/17 (5.88%)  5/43 (11.63%)  0/11 (0.00%) 
White blood cell count increased  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Metabolism and nutrition disorders       
Decreased appetite  1  4/17 (23.53%)  23/43 (53.49%)  2/11 (18.18%) 
Dehydration  1  1/17 (5.88%)  4/43 (9.30%)  0/11 (0.00%) 
Hypercholesterolaemia  1  2/17 (11.76%)  2/43 (4.65%)  0/11 (0.00%) 
Hyperglycaemia  1  2/17 (11.76%)  4/43 (9.30%)  0/11 (0.00%) 
Hypernatraemia  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Hypertriglyceridaemia  1  1/17 (5.88%)  6/43 (13.95%)  0/11 (0.00%) 
Hyperuricaemia  1  1/17 (5.88%)  1/43 (2.33%)  0/11 (0.00%) 
Hypoalbuminaemia  1  2/17 (11.76%)  7/43 (16.28%)  2/11 (18.18%) 
Hypocalcaemia  1  1/17 (5.88%)  1/43 (2.33%)  0/11 (0.00%) 
Hypokalaemia  1  0/17 (0.00%)  13/43 (30.23%)  0/11 (0.00%) 
Hyponatraemia  1  0/17 (0.00%)  4/43 (9.30%)  0/11 (0.00%) 
Hypophosphataemia  1  2/17 (11.76%)  4/43 (9.30%)  0/11 (0.00%) 
Malnutrition  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/17 (0.00%)  5/43 (11.63%)  0/11 (0.00%) 
Arthritis  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Back pain  1  1/17 (5.88%)  3/43 (6.98%)  0/11 (0.00%) 
Bone pain  1  0/17 (0.00%)  1/43 (2.33%)  1/11 (9.09%) 
Clubbing  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Muscle spasms  1  1/17 (5.88%)  2/43 (4.65%)  0/11 (0.00%) 
Musculoskeletal chest pain  1  0/17 (0.00%)  3/43 (6.98%)  2/11 (18.18%) 
Musculoskeletal pain  1  0/17 (0.00%)  4/43 (9.30%)  0/11 (0.00%) 
Pain in extremity  1  1/17 (5.88%)  5/43 (11.63%)  0/11 (0.00%) 
Pain in jaw  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Sensation of heaviness  1  1/17 (5.88%)  0/43 (0.00%)  1/11 (9.09%) 
Spinal pain  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Metastases to liver  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Nervous system disorders       
Dizziness  1  2/17 (11.76%)  8/43 (18.60%)  0/11 (0.00%) 
Dysaesthesia  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Dysgeusia  1  0/17 (0.00%)  13/43 (30.23%)  1/11 (9.09%) 
Headache  1  2/17 (11.76%)  10/43 (23.26%)  0/11 (0.00%) 
Hypoaesthesia  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Neuropathy peripheral  1  1/17 (5.88%)  1/43 (2.33%)  0/11 (0.00%) 
Somnolence  1  1/17 (5.88%)  1/43 (2.33%)  0/11 (0.00%) 
Psychiatric disorders       
Anxiety  1  1/17 (5.88%)  3/43 (6.98%)  2/11 (18.18%) 
Insomnia  1  1/17 (5.88%)  7/43 (16.28%)  1/11 (9.09%) 
Renal and urinary disorders       
Dysuria  1  1/17 (5.88%)  1/43 (2.33%)  0/11 (0.00%) 
Haematuria  1  1/17 (5.88%)  6/43 (13.95%)  0/11 (0.00%) 
Nocturia  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Proteinuria  1  2/17 (11.76%)  4/43 (9.30%)  1/11 (9.09%) 
Renal failure  1  1/17 (5.88%)  0/43 (0.00%)  1/11 (9.09%) 
Renal failure acute  1  1/17 (5.88%)  1/43 (2.33%)  0/11 (0.00%) 
Reproductive system and breast disorders       
Pelvic pain  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  1/17 (5.88%)  10/43 (23.26%)  1/11 (9.09%) 
Dysphonia  1  0/17 (0.00%)  2/43 (4.65%)  1/11 (9.09%) 
Dyspnoea  1  5/17 (29.41%)  14/43 (32.56%)  1/11 (9.09%) 
Dyspnoea exertional  1  2/17 (11.76%)  2/43 (4.65%)  0/11 (0.00%) 
Epistaxis  1  2/17 (11.76%)  12/43 (27.91%)  1/11 (9.09%) 
Haemoptysis  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Lung consolidation  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Oropharyngeal pain  1  1/17 (5.88%)  5/43 (11.63%)  1/11 (9.09%) 
Pleural effusion  1  1/17 (5.88%)  0/43 (0.00%)  1/11 (9.09%) 
Productive cough  1  0/17 (0.00%)  1/43 (2.33%)  1/11 (9.09%) 
Pulmonary embolism  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Skin and subcutaneous tissue disorders       
Acne  1  0/17 (0.00%)  1/43 (2.33%)  1/11 (9.09%) 
Alopecia  1  1/17 (5.88%)  2/43 (4.65%)  0/11 (0.00%) 
Dermatitis contact  1  0/17 (0.00%)  0/43 (0.00%)  1/11 (9.09%) 
Dry skin  1  1/17 (5.88%)  10/43 (23.26%)  0/11 (0.00%) 
Erythema  1  0/17 (0.00%)  5/43 (11.63%)  1/11 (9.09%) 
Hyperhidrosis  1  1/17 (5.88%)  0/43 (0.00%)  0/11 (0.00%) 
Nail toxicity  1  1/17 (5.88%)  1/43 (2.33%)  0/11 (0.00%) 
Palmar-plantar erythrodysaesthesia syndrome  1  1/17 (5.88%)  2/43 (4.65%)  0/11 (0.00%) 
Pruritus  1  0/17 (0.00%)  4/43 (9.30%)  0/11 (0.00%) 
Rash  1  4/17 (23.53%)  12/43 (27.91%)  1/11 (9.09%) 
Rash maculo-papular  1  0/17 (0.00%)  5/43 (11.63%)  0/11 (0.00%) 
Skin toxicity  1  1/17 (5.88%)  0/43 (0.00%)  1/11 (9.09%) 
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
Phone: +1 (424) 248-6500
Responsible Party: Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier: NCT01827267     History of Changes
Other Study ID Numbers: PUMA-NER-4201
2012-004743-68 ( EudraCT Number )
First Submitted: April 1, 2013
First Posted: April 9, 2013
Results First Submitted: August 8, 2017
Results First Posted: September 11, 2017
Last Update Posted: July 3, 2018