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Temsirolimus Plus Neratinib for Patients With Metastatic HER2-Amplified or Triple Negative Breast Cancer

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ClinicalTrials.gov Identifier: NCT01111825
Recruitment Status : Completed
First Posted : April 28, 2010
Results First Posted : November 7, 2017
Last Update Posted : September 26, 2018
Sponsor:
Information provided by (Responsible Party):
Puma Biotechnology, Inc.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Breast Cancer
Interventions Drug: Temsirolimus
Drug: Neratinib
Enrollment 99
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Phase 1 Phase 2 Triple -ve Phase 2 HER2+ Phase 2 HER2+ Dose Esc
Hide Arm/Group Description Phase I, HER - Amplified (HER2-Positive) cohort Phase 2, Triple - Negative cohort Phase 2, HER2 - Amplified (HER2-Positive) cohort Phase 2, HER2 - Positive cohort with dose escalation
Period Title: Overall Study
Started 8 6 37 48
Completed [1] 5 5 29 27
Not Completed 3 1 8 21
Reason Not Completed
Withdrawal by Subject             0             0             1             0
Lost to Follow-up             0             0             3             1
Adverse Event             2             1             4             0
Disease Progression             1             0             0             0
Discontinuation by Sponsor             0             0             0             20
[1]
Completed means completed study or died.
Arm/Group Title Phase 1 Phase 2 Triple -ve Phase 2 HER2+ Phase 2 HER2+ Dose Esc Total
Hide Arm/Group Description Phase I, HER - Amplified (HER2-Positive) cohort Phase 2, Triple - Negative cohort Phase 2, HER2 - Amplified (HER2-Positive) cohort Phase 2, HER2 - Positive cohort with dose escalation Total of all reporting groups
Overall Number of Baseline Participants 8 6 37 48 99
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 37 participants 48 participants 99 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
7
  87.5%
5
  83.3%
34
  91.9%
39
  81.3%
85
  85.9%
>=65 years
1
  12.5%
1
  16.7%
3
   8.1%
9
  18.8%
14
  14.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 8 participants 6 participants 37 participants 48 participants 99 participants
47.5  (10.4) 53.5  (13.0) 52.0  (8.3) 53.2  (11.0) 52.3  (10.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 6 participants 37 participants 48 participants 99 participants
Female
8
 100.0%
6
 100.0%
37
 100.0%
47
  97.9%
98
  99.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.1%
1
   1.0%
1.Primary Outcome
Title Objective Response Rate (ORR) (Phase II)
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 enrollment date to first documented response, or last tumor assessment, assessed up to two years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population (all enrolled subjects) for the Phase II portion of the study. Per protocol, Phase I data was not included in efficacy analysis.
Arm/Group Title Phase 2 Triple -ve Phase 2 HER2+ Phase 2 HER2+ Dose Esc
Hide Arm/Group Description:
Phase 2, Triple - Negative cohort
Phase 2, HER2 - Amplified (HER2-Positive) cohort
Phase 2, HER2 - Positive cohort with dose escalation
Overall Number of Participants Analyzed 6 37 48
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
5
  13.5%
14
  29.2%
2.Secondary Outcome
Title Clinical Benefit Rate (CBR)
Hide Description

Defined as the proportion of patients who achieved objective response (CR or PR) or SD for at least 24 weeks 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; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Clinical Benefit (CB) = CR + PR + SD >= 24 weeks.

Time Frame From enrollment date to first documented response, or last tumor assessment, assessed up to two years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population (all enrolled subjects) for the Phase II portion of the study. Per protocol, Phase I data was not included in efficacy analysis.
Arm/Group Title Phase 2 Triple -ve Phase 2 HER2+ Phase 2 HER2+ Dose Esc
Hide Arm/Group Description:
Phase 2, Triple - Negative cohort
Phase 2, HER2 - Amplified (HER2-Positive) cohort
Phase 2, HER2 - Positive cohort with dose escalation
Overall Number of Participants Analyzed 6 37 48
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
8
  21.6%
19
  39.6%
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 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; Progressive Disease (PD), At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, and/or the appearance of one or more new lesions.
Time Frame From first response to first PD or death, assessed up to two years.
Hide Outcome Measure Data
Hide Analysis Population Description

Patients who were enrolled and responded in the Phase II portion of the study. Per protocol, Phase I data was not included in efficacy analysis.

Note, no subject in Phase II triple negative cohort had a response. Therefore, no participants were analyzed for DOR.

Arm/Group Title Phase 2 Triple -ve Phase 2 HER2+ Phase 2 HER2+ Dose Esc
Hide Arm/Group Description:
Phase 2, Triple - Negative cohort
Phase 2, HER2 - Amplified (HER2-Positive) cohort
Phase 2, HER2 - Positive cohort with dose escalation
Overall Number of Participants Analyzed 0 5 14
Measure Type: Count of Participants
Unit of Measure: Participants
0 to <3 months 0
1
  20.0%
2
  14.3%
3 to <6 months 0
2
  40.0%
1
   7.1%
6 to <9 months 0
0
   0.0%
6
  42.9%
9 to <12 months 0
2
  40.0%
2
  14.3%
12+ months 0
0
   0.0%
3
  21.4%
4.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description Defined as time from date of enrollment until the first disease recurrence or progression 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 date of enrollment until the date of first documented progression, or date of death from any cause, whichever came first, assessed up to two years.
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population (all enrolled subjects) for the Phase II portion of the study. Per protocol, Phase I data was not included in efficacy analysis.
Arm/Group Title Phase 2 Triple -ve Phase 2 HER2+ Phase 2 HER2+ Dose Esc
Hide Arm/Group Description:
Phase 2, Triple - Negative cohort
Phase 2, HER2 - Amplified (HER2-Positive) cohort
Phase 2, HER2 - Positive cohort with dose escalation
Overall Number of Participants Analyzed 6 37 48
Median (95% Confidence Interval)
Unit of Measure: months
1.8
(1.8 to 2.0)
4.8
(2.7 to 8.4)
6.0
(3.7 to 8.3)
5.Secondary Outcome
Title Overall Survival (OS)
Hide Description Defined as the time from enrollment to death due to any cause; censored at the date last known alive.
Time Frame From enrollment to date of death from any cause, or end of long term follow-up, assessed up to three years.
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population (all enrolled subjects) for the Phase II portion of the study. Per protocol, Phase I data was not included in efficacy analysis.
Arm/Group Title Phase 2 HER2+ Dose Esc
Hide Arm/Group Description:
Phase 2, HER2 - Positive cohort with dose escalation
Overall Number of Participants Analyzed 48
Median (95% Confidence Interval)
Unit of Measure: months
17.8 [1] 
(13.4 to NA)
[1]
Upper limit of confidence interval is not estimable.
Time Frame From first dose through 28 days after last dose, assessed up to two years.
Adverse Event Reporting Description Safety Population
 
Arm/Group Title Phase 1 Phase 2 Triple -ve Phase 2 HER2+ Phase 2 HER2+ Dose Esc
Hide Arm/Group Description Phase I, HER - Amplified (HER2-Positive) cohort Phase 2, Triple - Negative cohort Phase 2, HER2 - Amplified (HER2-Positive) cohort Phase 2, HER2 - Positive cohort with dose escalation
All-Cause Mortality
Phase 1 Phase 2 Triple -ve Phase 2 HER2+ Phase 2 HER2+ Dose Esc
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Phase 1 Phase 2 Triple -ve Phase 2 HER2+ Phase 2 HER2+ Dose Esc
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/8 (37.50%)   2/6 (33.33%)   12/37 (32.43%)   20/48 (41.67%) 
Blood and lymphatic system disorders         
Anaemia  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  1/48 (2.08%) 
Febrile neutropenia  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  0/48 (0.00%) 
Polycythaemia  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  0/48 (0.00%) 
Cardiac disorders         
Acute coronary syndrome  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  1/48 (2.08%) 
Ear and labyrinth disorders         
Vertigo  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  1/48 (2.08%) 
Eye disorders         
Eyelid oedema  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  0/48 (0.00%) 
Gastrointestinal disorders         
Constipation  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  0/48 (0.00%) 
Diarrhoea  1  0/8 (0.00%)  0/6 (0.00%)  3/37 (8.11%)  2/48 (4.17%) 
Nausea  1  0/8 (0.00%)  0/6 (0.00%)  3/37 (8.11%)  0/48 (0.00%) 
Stomatitis  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  1/48 (2.08%) 
Upper gastrointestinal haemorrhage  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  1/48 (2.08%) 
Vomiting  1  0/8 (0.00%)  0/6 (0.00%)  2/37 (5.41%)  3/48 (6.25%) 
General disorders         
Chest pain  1  0/8 (0.00%)  1/6 (16.67%)  0/37 (0.00%)  0/48 (0.00%) 
Pyrexia  1  0/8 (0.00%)  0/6 (0.00%)  2/37 (5.41%)  1/48 (2.08%) 
Infections and infestations         
Cellulitis  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  1/48 (2.08%) 
Empyema  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  0/48 (0.00%) 
Lower respiratory tract infection  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  1/48 (2.08%) 
Pneumonia  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  1/48 (2.08%) 
Sepsis  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  0/48 (0.00%) 
Urinary tract infection  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  0/48 (0.00%) 
Injury, poisoning and procedural complications         
Humerus fracture  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  1/48 (2.08%) 
Investigations         
Blood alkaline phosphatase increased  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  1/48 (2.08%) 
Blood creatine phosphokinase increased  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  1/48 (2.08%) 
Electrocardiogram ST segment depression  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  1/48 (2.08%) 
Gamma-glutamyltransferase increased  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  1/48 (2.08%) 
Haemoglobin increased  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  0/48 (0.00%) 
Transaminases increased  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  1/48 (2.08%) 
Metabolism and nutrition disorders         
Dehydration  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  0/48 (0.00%) 
Failure to thrive  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  0/48 (0.00%) 
Hypokalaemia  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  0/48 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back pain  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  1/48 (2.08%) 
Muscular weakness  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  1/48 (2.08%) 
Musculoskeletal chest pain  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  1/48 (2.08%) 
Nervous system disorders         
Cerebral disorder  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  1/48 (2.08%) 
Dizziness  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  2/48 (4.17%) 
Headache  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  1/48 (2.08%) 
Neuropathy peripheral  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  0/48 (0.00%) 
Spinal cord compression  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  0/48 (0.00%) 
Syncope  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  0/48 (0.00%) 
Psychiatric disorders         
Mental status changes  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  0/48 (0.00%) 
Renal and urinary disorders         
Renal failure  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  1/48 (2.08%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  0/8 (0.00%)  1/6 (16.67%)  0/37 (0.00%)  0/48 (0.00%) 
Dyspnoea  1  0/8 (0.00%)  2/6 (33.33%)  0/37 (0.00%)  0/48 (0.00%) 
Pleural effusion  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  2/48 (4.17%) 
Skin and subcutaneous tissue disorders         
Rash  1  1/8 (12.50%)  0/6 (0.00%)  1/37 (2.70%)  0/48 (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%
Phase 1 Phase 2 Triple -ve Phase 2 HER2+ Phase 2 HER2+ Dose Esc
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/8 (100.00%)   6/6 (100.00%)   37/37 (100.00%)   48/48 (100.00%) 
Blood and lymphatic system disorders         
Anaemia  1  0/8 (0.00%)  0/6 (0.00%)  2/37 (5.41%)  10/48 (20.83%) 
Neutropenia  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  3/48 (6.25%) 
Thrombocytopenia  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  4/48 (8.33%) 
Ear and labyrinth disorders         
Ear pain  1  0/8 (0.00%)  1/6 (16.67%)  0/37 (0.00%)  0/48 (0.00%) 
Eye disorders         
Dry eye  1  1/8 (12.50%)  0/6 (0.00%)  3/37 (8.11%)  2/48 (4.17%) 
Vision blurred  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  0/48 (0.00%) 
Gastrointestinal disorders         
Abdominal pain  1  0/8 (0.00%)  0/6 (0.00%)  5/37 (13.51%)  3/48 (6.25%) 
Abdominal pain upper  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  8/48 (16.67%) 
Cheilitis  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  3/48 (6.25%) 
Constipation  1  2/8 (25.00%)  2/6 (33.33%)  7/37 (18.92%)  21/48 (43.75%) 
Diarrhoea  1  7/8 (87.50%)  5/6 (83.33%)  35/37 (94.59%)  40/48 (83.33%) 
Dry mouth  1  1/8 (12.50%)  0/6 (0.00%)  2/37 (5.41%)  6/48 (12.50%) 
Dyspepsia  1  3/8 (37.50%)  0/6 (0.00%)  1/37 (2.70%)  2/48 (4.17%) 
Gastrooesophageal reflux disease  1  0/8 (0.00%)  1/6 (16.67%)  2/37 (5.41%)  2/48 (4.17%) 
Glossodynia  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  0/48 (0.00%) 
Mouth ulceration  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  9/48 (18.75%) 
Nausea  1  6/8 (75.00%)  5/6 (83.33%)  18/37 (48.65%)  20/48 (41.67%) 
Stomatitis  1  5/8 (62.50%)  4/6 (66.67%)  25/37 (67.57%)  29/48 (60.42%) 
Vomiting  1  3/8 (37.50%)  3/6 (50.00%)  9/37 (24.32%)  23/48 (47.92%) 
General disorders         
Asthenia  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  18/48 (37.50%) 
Chest discomfort  1  0/8 (0.00%)  1/6 (16.67%)  0/37 (0.00%)  0/48 (0.00%) 
Chest pain  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  0/48 (0.00%) 
Chills  1  0/8 (0.00%)  0/6 (0.00%)  2/37 (5.41%)  1/48 (2.08%) 
Fatigue  1  6/8 (75.00%)  3/6 (50.00%)  20/37 (54.05%)  9/48 (18.75%) 
Oedema peripheral  1  2/8 (25.00%)  1/6 (16.67%)  2/37 (5.41%)  9/48 (18.75%) 
Pain  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  3/48 (6.25%) 
Pyrexia  1  2/8 (25.00%)  1/6 (16.67%)  6/37 (16.22%)  4/48 (8.33%) 
Immune system disorders         
Hypersensitivity  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  0/48 (0.00%) 
Infections and infestations         
Influenza  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  3/48 (6.25%) 
Localised infection  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  3/48 (6.25%) 
Nasopharyngitis  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  5/48 (10.42%) 
Onychomycosis  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  1/48 (2.08%) 
Paronychia  1  0/8 (0.00%)  0/6 (0.00%)  4/37 (10.81%)  4/48 (8.33%) 
Pharyngitis  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  1/48 (2.08%) 
Rhinitis  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  3/48 (6.25%) 
Upper respiratory tract infection  1  1/8 (12.50%)  0/6 (0.00%)  1/37 (2.70%)  3/48 (6.25%) 
Urinary tract infection  1  0/8 (0.00%)  0/6 (0.00%)  3/37 (8.11%)  4/48 (8.33%) 
Injury, poisoning and procedural complications         
Fall  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  3/48 (6.25%) 
Stoma site ulcer  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  0/48 (0.00%) 
Investigations         
Alanine aminotransferase increased  1  0/8 (0.00%)  0/6 (0.00%)  2/37 (5.41%)  2/48 (4.17%) 
Aspartate aminotransferase increased  1  0/8 (0.00%)  0/6 (0.00%)  2/37 (5.41%)  3/48 (6.25%) 
Blood alkaline phosphatase increased  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  4/48 (8.33%) 
Blood creatinine increased  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  3/48 (6.25%) 
Haemoglobin decreased  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  3/48 (6.25%) 
Monocyte count increased  1  0/8 (0.00%)  1/6 (16.67%)  0/37 (0.00%)  0/48 (0.00%) 
Platelet count decreased  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  4/48 (8.33%) 
Weight decreased  1  3/8 (37.50%)  2/6 (33.33%)  5/37 (13.51%)  6/48 (12.50%) 
Weight increased  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  0/48 (0.00%) 
Metabolism and nutrition disorders         
Decreased appetite  1  4/8 (50.00%)  1/6 (16.67%)  6/37 (16.22%)  19/48 (39.58%) 
Dehydration  1  1/8 (12.50%)  0/6 (0.00%)  1/37 (2.70%)  1/48 (2.08%) 
Hyperglycaemia  1  0/8 (0.00%)  0/6 (0.00%)  2/37 (5.41%)  1/48 (2.08%) 
Hypertriglyceridaemia  1  0/8 (0.00%)  0/6 (0.00%)  0/37 (0.00%)  4/48 (8.33%) 
Hypokalaemia  1  1/8 (12.50%)  0/6 (0.00%)  3/37 (8.11%)  1/48 (2.08%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  4/8 (50.00%)  3/6 (50.00%)  6/37 (16.22%)  5/48 (10.42%) 
Back pain  1  1/8 (12.50%)  2/6 (33.33%)  6/37 (16.22%)  4/48 (8.33%) 
Bone pain  1  1/8 (12.50%)  1/6 (16.67%)  0/37 (0.00%)  0/48 (0.00%) 
Joint stiffness  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  0/48 (0.00%) 
Muscle spasms  1  0/8 (0.00%)  1/6 (16.67%)  1/37 (2.70%)  4/48 (8.33%) 
Muscular weakness  1  1/8 (12.50%)  0/6 (0.00%)  1/37 (2.70%)  0/48 (0.00%) 
Musculoskeletal chest pain  1  1/8 (12.50%)  0/6 (0.00%)  3/37 (8.11%)  2/48 (4.17%) 
Musculoskeletal pain  1  1/8 (12.50%)  0/6 (0.00%)  1/37 (2.70%)  4/48 (8.33%) 
Myalgia  1  0/8 (0.00%)  1/6 (16.67%)  2/37 (5.41%)  2/48 (4.17%) 
Neck pain  1  1/8 (12.50%)  1/6 (16.67%)  1/37 (2.70%)  0/48 (0.00%) 
Pain in extremity  1  2/8 (25.00%)  1/6 (16.67%)  2/37 (5.41%)  6/48 (12.50%) 
Nervous system disorders         
Dizziness  1  1/8 (12.50%)  0/6 (0.00%)  6/37 (16.22%)  4/48 (8.33%) 
Dysgeusia  1  0/8 (0.00%)  1/6 (16.67%)  4/37 (10.81%)  1/48 (2.08%) 
Headache  1  3/8 (37.50%)  2/6 (33.33%)  2/37 (5.41%)  11/48 (22.92%) 
Hypoaesthesia  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  0/48 (0.00%) 
Migraine  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  0/48 (0.00%) 
Neuralgia  1  1/8 (12.50%)  1/6 (16.67%)  1/37 (2.70%)  0/48 (0.00%) 
Neuropathy peripheral  1  2/8 (25.00%)  0/6 (0.00%)  7/37 (18.92%)  1/48 (2.08%) 
Paraesthesia  1  0/8 (0.00%)  1/6 (16.67%)  5/37 (13.51%)  1/48 (2.08%) 
Peripheral sensory neuropathy  1  1/8 (12.50%)  0/6 (0.00%)  1/37 (2.70%)  0/48 (0.00%) 
Psychiatric disorders         
Insomnia  1  0/8 (0.00%)  1/6 (16.67%)  0/37 (0.00%)  4/48 (8.33%) 
Renal and urinary disorders         
Pollakiuria  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  0/48 (0.00%) 
Urinary incontinence  1  1/8 (12.50%)  0/6 (0.00%)  1/37 (2.70%)  1/48 (2.08%) 
Reproductive system and breast disorders         
Breast pain  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  1/48 (2.08%) 
Vulvovaginal dryness  1  1/8 (12.50%)  0/6 (0.00%)  3/37 (8.11%)  0/48 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  2/8 (25.00%)  2/6 (33.33%)  4/37 (10.81%)  9/48 (18.75%) 
Dysphonia  1  0/8 (0.00%)  0/6 (0.00%)  1/37 (2.70%)  3/48 (6.25%) 
Dyspnoea  1  1/8 (12.50%)  3/6 (50.00%)  3/37 (8.11%)  9/48 (18.75%) 
Dyspnoea exertional  1  0/8 (0.00%)  0/6 (0.00%)  2/37 (5.41%)  1/48 (2.08%) 
Epistaxis  1  0/8 (0.00%)  1/6 (16.67%)  3/37 (8.11%)  10/48 (20.83%) 
Nasal dryness  1  0/8 (0.00%)  1/6 (16.67%)  0/37 (0.00%)  0/48 (0.00%) 
Oropharyngeal pain  1  0/8 (0.00%)  1/6 (16.67%)  1/37 (2.70%)  5/48 (10.42%) 
Pleural effusion  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  0/48 (0.00%) 
Rhinitis allergic  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  0/48 (0.00%) 
Skin and subcutaneous tissue disorders         
Dermatitis acneiform  1  2/8 (25.00%)  3/6 (50.00%)  4/37 (10.81%)  0/48 (0.00%) 
Dry skin  1  4/8 (50.00%)  2/6 (33.33%)  7/37 (18.92%)  4/48 (8.33%) 
Hair texture abnormal  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  0/48 (0.00%) 
Nail disorder  1  0/8 (0.00%)  0/6 (0.00%)  2/37 (5.41%)  2/48 (4.17%) 
Nail dystrophy  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  0/48 (0.00%) 
Palmar-plantar erythrodysaesthesia syndrome  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  5/48 (10.42%) 
Pruritus  1  1/8 (12.50%)  2/6 (33.33%)  4/37 (10.81%)  7/48 (14.58%) 
Rash  1  3/8 (37.50%)  0/6 (0.00%)  17/37 (45.95%)  21/48 (43.75%) 
Skin hyperpigmentation  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  1/48 (2.08%) 
Skin reaction  1  0/8 (0.00%)  1/6 (16.67%)  0/37 (0.00%)  0/48 (0.00%) 
Swelling face  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  0/48 (0.00%) 
Vascular disorders         
Hot flush  1  2/8 (25.00%)  0/6 (0.00%)  1/37 (2.70%)  1/48 (2.08%) 
Lymphoedema  1  1/8 (12.50%)  0/6 (0.00%)  1/37 (2.70%)  2/48 (4.17%) 
Post thrombotic syndrome  1  1/8 (12.50%)  0/6 (0.00%)  0/37 (0.00%)  0/48 (0.00%) 
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: NCT01111825     History of Changes
Other Study ID Numbers: 10-005
First Submitted: April 22, 2010
First Posted: April 28, 2010
Results First Submitted: August 10, 2017
Results First Posted: November 7, 2017
Last Update Posted: September 26, 2018