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Nexavar® Versus Placebo in Locally Advanced/Metastatic RAI-Refractory Differentiated Thyroid Cancer

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ClinicalTrials.gov Identifier: NCT00984282
Recruitment Status : Completed
First Posted : September 25, 2009
Results First Posted : December 10, 2013
Last Update Posted : September 13, 2018
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Thyroid Neoplasms
Interventions Drug: Sorafenib (Nexavar, BAY43-9006)
Drug: Placebo
Enrollment 417
Recruitment Details  
Pre-assignment Details Of 556 screened participants, 137 failed screening, 207 were randomized to receive sorafenib, 210 were randomized to placebo.
Arm/Group Title DB Sorafenib First, Then Option of OL Sorafenib Treatment DB Placebo First, Then Option of OL Sorafenib Treatment
Hide Arm/Group Description Double-blind period: Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (12 hours apart without food), 28 days comprise a cycle. Open-label (OL) period: Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (12 hours apart without food), 28 days comprise a cycle. Double-blind period: participants received matching placebo tablets orally twice daily, 28 days comprised a cycle. Open-label (OL) period: participants on placebo who switched to sorafenib, received sorafenib 400 mg (2 x 200 mg) orally twice daily, 28 days comprise a cycle.
Period Title: Double Blind Treatment
Started 207 210
Received Treatment 207 [1] 209 [2]
Completed 103 172
Not Completed 104 38
Reason Not Completed
Adverse Event             40             6
Progression, recurrence or relapse             25             3
Physician Decision             1             2
Noncompliance with study medication             3             0
Progression by clinical judgment             2             0
Withdrawal by Subject             13             18
Lost to Follow-up             3             0
Death             8             4
Not treated             0             1
Switched to commercial drug             6             1
protocol driven decision point             1             1
Radiological and clinical progression             0             1
Transferred to treat. continuation study             2             1
[1]
Subjects at Risk/Safety Population - in RG1 (RG= Reporting Group for Safety Data)
[2]
Subjects at Risk/Safety Population - in RG2 (RG= Reporting Group for Safety Data)
Period Title: Open-label Treatment
Started 86 161
Received Treatment 86 [1] 161 [2]
Completed 0 0
Not Completed 86 161
Reason Not Completed
Adverse Event             20             30
Withdrawal by Subject             6             21
Death             7             15
Progression, recurrence or relapse             40             82
Lost to Follow-up             1             1
Patient convenience             1             0
Non-compliant with study medication             1             0
Target lesion removed             0             1
Protocol driven decision point             1             1
Transferred to treat. continuation study             2             3
Switched to commercial drug             6             7
Physician Decision             1             0
[1]
Subjects at Risk/Safety Population - in RG3 (RG= Reporting Group for Safety Data)
[2]
Subjects at Risk/Safety Population - in RG4 (RG= Reporting Group for Safety Data)
Period Title: Long Term Follow-up
Started 72 [1] 124 [1]
Completed 3 4
Not Completed 69 120
Reason Not Completed
Withdrawal by Subject             8             14
Death             27             68
Lost to Follow-up             3             6
Protocol driven decision point             25             26
Transferred to treat. continuation study             2             3
Switched to commercial drug             4             2
Disease prog., recurrence or relapse             0             1
[1]
Participants entered long-term follow-up if terminated double-blind or open-label periods
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo Total
Hide Arm/Group Description Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (12 hours apart without food), 28 days comprise a cycle. Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle. Total of all reporting groups
Overall Number of Baseline Participants 207 210 417
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 207 participants 210 participants 417 participants
61.5  (11.2) 62.0  (11.7) 61.8  (11.4)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 207 participants 210 participants 417 participants
< 60 years
80
  38.6%
81
  38.6%
161
  38.6%
>= 60 years
127
  61.4%
129
  61.4%
256
  61.4%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 207 participants 210 participants 417 participants
Female
103
  49.8%
115
  54.8%
218
  52.3%
Male
104
  50.2%
95
  45.2%
199
  47.7%
Geographic region  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 207 participants 210 participants 417 participants
Europe
124
  59.9%
125
  59.5%
249
  59.7%
North America
36
  17.4%
36
  17.1%
72
  17.3%
Asia
47
  22.7%
49
  23.3%
96
  23.0%
ECOG (Eastern Cooperative Oncology Group) performance status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 207 participants 210 participants 417 participants
Missing
1
   0.5%
1
   0.5%
2
   0.5%
0
130
  62.8%
129
  61.4%
259
  62.1%
1
69
  33.3%
74
  35.2%
143
  34.3%
2
7
   3.4%
6
   2.9%
13
   3.1%
[1]
Measure Description: The ECOG PS required for the study was 0 (fully active), 1 (restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature), or 2 (ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours)
Site of target/nontarget lesions at baseline - organ class   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 207 participants 210 participants 417 participants
Lung 178 181 359
Lymph node 113 101 214
Bone 57 56 113
[1]
Measure Description: Participants could have had more than one site.
1.Primary Outcome
Title Progression-free Survival (PFS) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation
Hide Description PFS=time from randomization to first observed disease progression (radiological according to central assessment or clinical due to bone irradiation, whichever is earlier), or death due to any cause, if death occurred before progression. Progression was assessed by RECIST criteria, version 1.0, modified for bone lesions. PFS for participants without disease progression or death at the time of analysis or unblinding were censored at the last date of tumor assessment before unblinding. Participants with no tumor evaluation after baseline were censored at Day 1. PD (Progression Disease)=At least a 20% increase in sum of longest diameters (LD) of measured lesions taking as reference the smallest sum LD on study since the treatment started or the appearance of 1 or more new lesions. New lesions also constituted PD. In exceptional circumstances, unequivocal progression of a nonmeasured lesion may have been accepted as evidence of disease progression in participants with measurable disease.
Time Frame Final analysis to be performed when approximately 267 progression-free survival events (centrally assessed) had occurred, study duration approximately three years
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS). The primary population for efficacy analysis was the FAS. The FAS was identical to the intent-to-treat (ITT) population, which was defined as all randomized participants. Participants were analyzed as randomized.
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Hide Arm/Group Description:
Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (12 hours apart without food), 28 days comprise a cycle
Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle
Overall Number of Participants Analyzed 207 210
Median (95% Confidence Interval)
Unit of Measure: Days
329
(278 to 393)
175
(160 to 238)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sorafenib (Nexavar, BAY43-9006), Placebo
Comments The two treatment groups were compared using a stratified one-sided log rank test with an overall alpha of 0.01 stratified by age group and region. The null hypothesis that both treatment arms have the same PFS distribution will be tested against the alternative hypothesis that the distribution of PFS times in the sorafenib arm is different from the control arm according to the Lehmann alternative, which is equivalent to the assumption of proportional hazards of the treatment arms.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments stratified by age group (< 60 years, >= 60 years) and region (Europe, North-America, Asia)
Method Log Rank
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sorafenib (Nexavar, BAY43-9006), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Cox
Comments stratified by age group and region
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.587
Confidence Interval (2-Sided) 95%
0.454 to 0.758
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival was defined as the time (days) from date of randomization to date of death due to any cause. Subjects still alive at the time of analysis were censored at their date of last contact. Since the median value could not be estimated due to censored data, the percentage of participants who died is presented.
Time Frame From randomization of the first subject until the database cut-off (30 AUG 2017), study duration approximately eight years
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS)
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Hide Arm/Group Description:
Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (12 hours apart without food), 28 days comprise a cycle
Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle
Overall Number of Participants Analyzed 207 210
Measure Type: Number
Unit of Measure: Percentage of participants
52.7 54.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sorafenib (Nexavar, BAY43-9006), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2892
Comments [Not Specified]
Method Log Rank
Comments stratified by age group and region
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sorafenib (Nexavar, BAY43-9006), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Cox
Comments stratified by age group and region
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.928
Confidence Interval (2-Sided) 95%
0.713 to 1.208
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Time to Progression (TTP) Based on Central Assessment Incl. Clinical Progression Due to Bone Irradiation
Hide Description Time to progression was defined at the time (days) from randomization to progression (based on central assessment [radiological and clinical progression due to bone irradiation])
Time Frame From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Hide Arm/Group Description:
Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (12 hours apart without food), 28 days comprise a cycle
Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle
Overall Number of Participants Analyzed 207 210
Median (95% Confidence Interval)
Unit of Measure: Days
337
(283 to 451)
175
(160 to 238)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sorafenib (Nexavar, BAY43-9006), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments stratified by age group and region
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sorafenib (Nexavar, BAY43-9006), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Cox
Comments stratified by age group and region
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.557
Confidence Interval (2-Sided) 95%
0.429 to 0.724
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Disease Control Rate (DCR) Based on Central Assessment
Hide Description Disease control rate was defined as the proportion of subjects whose best response was complete response (CR), partial response (PR), or stable disease (SD). Per Response Evaluation Criteria in Solid Tumors (RECIST) criteria, CR and PR were to be confirmed by another scan at least 4 weeks later; SD had to be documented at least 4 weeks after date of randomization. CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target). PR = At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum. SD = steady state of disease which is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time Frame From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol set (PPS). A participant was included in the PPS if he/she was randomized and was evaluable for tumor response based on imaging data, had exposure to study medication, and had no major protocol deviations.
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Hide Arm/Group Description:
Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (12 hours apart without food), 28 days comprise a cycle
Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle
Overall Number of Participants Analyzed 196 201
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
86.2
(80.6 to 90.7)
74.6
(68.0 to 80.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sorafenib (Nexavar, BAY43-9006), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments stratified by age group and region
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of response rates
Estimated Value 11.7
Confidence Interval (2-Sided) 95%
3.9 to 19.4
Estimation Comments Difference of disease control rates sorafenib minus placebo. Cochran-Mantel-Haenszel confidence interval stratified by age group and region
5.Secondary Outcome
Title Response Rate Based on Central Assessment
Hide Description Response rate was defined as the proportion of subjects whose best response was CR or PR. Per RECIST, CR and PR was to be confirmed by another scan at least 4 weeks later. CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target). PR = At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum.
Time Frame From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
Hide Outcome Measure Data
Hide Analysis Population Description
PPS
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Hide Arm/Group Description:
Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (12 hours apart without food), 28 days comprise a cycle
Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle
Overall Number of Participants Analyzed 196 201
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
12.24
(8.01 to 17.67)
0.5
(0.01 to 2.74)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sorafenib (Nexavar, BAY43-9006), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments stratified by age group and region
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in response rate
Estimated Value 11.8
Confidence Interval (2-Sided) 95%
7.0 to 16.5
Estimation Comments Difference of response rates sorafenib minus placebo. Cochran-Mantel-Haenszel confidence interval stratified by age group and region
6.Secondary Outcome
Title Duration of Response (DOR) Based on Central Assessment
Hide Description Duration of response was defined as the time from the first documented objective response of PR or CR, whichever was noted earlier, to disease progression or death (if death occurred before progression was documented). CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target). PR = At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum.
Time Frame From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
Hide Outcome Measure Data
Hide Analysis Population Description
FAS - responders only
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Hide Arm/Group Description:
Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (12 hours apart without food), 28 days comprise a cycle
Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle
Overall Number of Participants Analyzed 24 1
Median (Full Range)
Unit of Measure: Days
309
(226 to 505)
NA [1] 
(NA to NA)
[1]
only one subject with PR
7.Secondary Outcome
Title Maximum Percent Reduction in Target Lesion Size Based on Central Assessment
Hide Description The magnitude of change from baseline in target lesion size in evaluable participants with scans was determined.
Time Frame From randomization of the first subject until the database cut-off (31 Aug 2012), study duration approximately three years
Hide Outcome Measure Data
Hide Analysis Population Description
PPS
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Hide Arm/Group Description:
Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (12 hours apart without food), 28 days comprise a cycle
Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle
Overall Number of Participants Analyzed 196 201
Measure Type: Number
Unit of Measure: Percentage of participants
Reduction ≥ 30% 17.3 1.0
Reduction ≥ 20% but < 30% 15.3 1.5
Reduction ≥ 10% but < 20% 22.4 3.5
Reduction > 0% but < 10% 22.4 21.9
Growth ≥ 0% 12.8 62.7
Not assessed 9.7 9.5
8.Secondary Outcome
Title AUC(0-12h),ss (Area Under the Concentration Time Curve From Time 0 to 12 Hours at Steady State)
Hide Description Sorafenib AUC(0-12h),ss (area under the concentration time curve from time 0 to 12 hours at steady state) was estimated from the steady state plasma concentration.
Time Frame A single pharmacokinetic plasma sample was collected at steady state (after 14 days of uninterrupted, unmodified sorafenib dosing)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) analysis set=participants with PK data collected after 14 days of uninterrupted and unmodified dosing of sorafenib. If an interruption occurred within 14 days prior to the sample, no doses may be missed for 3 days prior to the sample, and no more than 3 doses could be missed 4 to 14 days prior to the sample collection date.
Arm/Group Title Sorafenib (Nexavar, BAY43-9006)
Hide Arm/Group Description:
Participants received 2 tablets of Sorafenib (2×200 mg) orally twice daily (12 hours apart without food), 28 days comprise a cycle
Overall Number of Participants Analyzed 113
Geometric Mean (Standard Deviation)
Unit of Measure: mg*h/L
75.4  (1.5)
Time Frame After signing the informed consent until the database cut-off 30 AUG 2017, study duration approximately eight years.
Adverse Event Reporting Description Abbreviations used: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Central Nervous System (CNS), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Cranial Nerve (CN), Range of Motion (ROM), Cerebrospinal Fluid (CSF), Genitourinary (GU).
 
Arm/Group Title Sorafenib (Double Blind Only) Placebo (Double Blind Only) Sorafenib, Open Label Only (Sorafenib Continued) Placebo, Open Label Only (Switch to Sorafenib)
Hide Arm/Group Description Reporting Group 1: Participants received 2 tablets of Sorafenib (2x200 mg) orally twice daily (12 hours apart without food), 28 days comprise a cycle. Data were collected from randomization to the end of double blind period Reporting Group 2: Participants received 2 tablets of Sorafenib-matching placebo orally twice daily (12 hours apart without food), 28 days comprise a cycle. Data were collected from randomization to the end of double-blind period. Reporting Group 3: Participants on sorafenib who continued OL sorafenib treat., received sorafenib 400 mg (2 x 200 mg) orally twice daily, 28 days comprise a cycle. Data were collected from the start of OL period to the data cutoff on 31 Aug Reporting Group 3: Participants on placebo who switched to sorafenib, received sorafenib 400 mg (2 x 200 mg) orally twice daily, 28 days comprise a cycle. Data were collected from the start of open label period to the data cutoff on 31 Aug 20
All-Cause Mortality
Sorafenib (Double Blind Only) Placebo (Double Blind Only) Sorafenib, Open Label Only (Sorafenib Continued) Placebo, Open Label Only (Switch to Sorafenib)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   71/207 (34.30%)      25/209 (11.96%)      38/86 (44.19%)      90/161 (55.90%)    
Show Serious Adverse Events Hide Serious Adverse Events
Sorafenib (Double Blind Only) Placebo (Double Blind Only) Sorafenib, Open Label Only (Sorafenib Continued) Placebo, Open Label Only (Switch to Sorafenib)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   87/207 (42.03%)      58/209 (27.75%)      51/86 (59.30%)      96/161 (59.63%)    
Blood and lymphatic system disorders         
Blood - Other * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Hemoglobin * 1  2/207 (0.97%)  2 0/209 (0.00%)  0 0/86 (0.00%)  0 2/161 (1.24%)  5
Lymphatics - Other * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Neutrophils * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Cardiac disorders         
Cardiac arrhythmia - Other * 1  1/207 (0.48%)  1 1/209 (0.48%)  1 1/86 (1.16%)  1 0/161 (0.00%)  0
Cardiac general - Other * 1  3/207 (1.45%)  3 0/209 (0.00%)  0 1/86 (1.16%)  1 4/161 (2.48%)  4
Cardiac ischemia/infarction * 1  2/207 (0.97%)  2 0/209 (0.00%)  0 2/86 (2.33%)  2 3/161 (1.86%)  4
Cardiopulmonary arrest * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Pericardial effusion * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Supraventricular arrhythmia, Atrial fibrillation * 1  0/207 (0.00%)  0 2/209 (0.96%)  2 1/86 (1.16%)  1 1/161 (0.62%)  1
Supraventricular arrhythmia, Atrial flutter * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  1 0/161 (0.00%)  0
Supraventricular arrhythmia, Supraventricular tachycardia * 1  2/207 (0.97%)  3 0/209 (0.00%)  0 2/86 (2.33%)  2 0/161 (0.00%)  0
Valvular heart disease * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  1 0/161 (0.00%)  0
Ventricular arrhythmia, Ventricular tachycardia * 1  0/207 (0.00%)  0 1/209 (0.48%)  1 0/86 (0.00%)  0 0/161 (0.00%)  0
Endocrine disorders         
Endocrine - Other * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 2/86 (2.33%)  3 3/161 (1.86%)  3
Hyperthyroidism * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Eye disorders         
Cataract * 1  1/207 (0.48%)  1 1/209 (0.48%)  1 0/86 (0.00%)  0 2/161 (1.24%)  4
Diplopia * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Ocular - Other * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Optic disc edema * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  1 0/161 (0.00%)  0
Gastrointestinal disorders         
Anorexia * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Colitis * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Dehydration * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 2/161 (1.24%)  2
Diarrhea * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Dysphagia * 1  2/207 (0.97%)  3 1/209 (0.48%)  1 2/86 (2.33%)  2 1/161 (0.62%)  1
Fistula, GI, Abdomen NOS * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Fistula, GI, Esophagus * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  1 0/161 (0.00%)  0
GI - Other * 1  0/207 (0.00%)  0 1/209 (0.48%)  1 0/86 (0.00%)  0 1/161 (0.62%)  1
Ileus * 1  1/207 (0.48%)  9 1/209 (0.48%)  1 1/86 (1.16%)  7 0/161 (0.00%)  0
Mucositis (functional/symptomatic), Oral cavity * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Mucositis (functional/symptomatic), Trachea * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  1 0/161 (0.00%)  0
Nausea * 1  0/207 (0.00%)  0 1/209 (0.48%)  1 0/86 (0.00%)  0 0/161 (0.00%)  0
Obstruction, GI, Esophagus * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Obstruction, GI, Gallbladder * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Perforation, GI, Colon * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Stricture, GI, Esophagus * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  1 0/161 (0.00%)  0
Teeth * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Ulcer, GI, Rectum * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Vomiting * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
General disorders         
Constitutional symptoms - Other * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 1/86 (1.16%)  1 1/161 (0.62%)  1
Death not associated with CTCAE term, Death NOS * 1  3/207 (1.45%)  3 0/209 (0.00%)  0 1/86 (1.16%)  1 0/161 (0.00%)  0
Death not associated with CTCAE term, Disease progression NOS * 1  2/207 (0.97%)  2 2/209 (0.96%)  2 3/86 (3.49%)  3 9/161 (5.59%)  9
Death not associated with CTCAE term, Multi-Organ Failure * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  1 1/161 (0.62%)  1
Death not associated with CTCAE term, Sudden death * 1  0/207 (0.00%)  0 1/209 (0.48%)  1 1/86 (1.16%)  1 0/161 (0.00%)  0
Fatigue * 1  3/207 (1.45%)  3 1/209 (0.48%)  1 0/86 (0.00%)  0 1/161 (0.62%)  1
Fever * 1  4/207 (1.93%)  4 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Flu-like syndrome * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
No code in CTCAE * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 2/86 (2.33%)  2 2/161 (1.24%)  2
Not coded yet * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  1 0/161 (0.00%)  0
Pain, Abdomen NOS * 1  2/207 (0.97%)  2 0/209 (0.00%)  0 1/86 (1.16%)  1 1/161 (0.62%)  1
Pain, Back * 1  1/207 (0.48%)  1 2/209 (0.96%)  2 0/86 (0.00%)  0 4/161 (2.48%)  4
Pain, Bone * 1  0/207 (0.00%)  0 1/209 (0.48%)  1 1/86 (1.16%)  1 2/161 (1.24%)  2
Pain, Chest wall * 1  0/207 (0.00%)  0 1/209 (0.48%)  1 0/86 (0.00%)  0 2/161 (1.24%)  2
Pain, Chest/Thorax NOS * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Pain, Dental/Teeth/peridontal * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Pain, Extremity - limb * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Pain, Head/Headache * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  1 0/161 (0.00%)  0
Pain, Joint * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Pain, Liver * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  1 0/161 (0.00%)  0
Pain, Lymph node * 1  0/207 (0.00%)  0 1/209 (0.48%)  1 0/86 (0.00%)  0 1/161 (0.62%)  1
Pain, Neuralgia/Peripheral nerve * 1  0/207 (0.00%)  0 1/209 (0.48%)  1 0/86 (0.00%)  0 0/161 (0.00%)  0
Pain, Pelvis * 1  1/207 (0.48%)  1 1/209 (0.48%)  1 0/86 (0.00%)  0 0/161 (0.00%)  0
Pain, Stomach * 1  0/207 (0.00%)  0 1/209 (0.48%)  1 0/86 (0.00%)  0 0/161 (0.00%)  0
Pain, Throat/Pharynx/Larynx * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Pain, Tumor pain * 1  2/207 (0.97%)  2 2/209 (0.96%)  2 1/86 (1.16%)  1 3/161 (1.86%)  3
Syndromes - Other * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  1 0/161 (0.00%)  0
Tumor flare * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Weight loss * 1  2/207 (0.97%)  2 1/209 (0.48%)  1 0/86 (0.00%)  0 0/161 (0.00%)  0
Hepatobiliary disorders         
Cholecystitis * 1  1/207 (0.48%)  1 1/209 (0.48%)  1 0/86 (0.00%)  0 0/161 (0.00%)  0
Hepatobiliary - Other * 1  1/207 (0.48%)  2 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Liver dysfunction * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Pancreatitis * 1  2/207 (0.97%)  2 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Immune system disorders         
Allergic reaction * 1  1/207 (0.48%)  4 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Allergy - Other * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Infections and infestations         
Colitis, infectious * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Infection (Documented clinically), Lung (Pneumonia) * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Infection (Documented clinically), Soft tissue NOS * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Infection (Documented clinically), Upper airway NOS * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  1 0/161 (0.00%)  0
Infection (Documented clinically), Wound * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Infection - Other * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 2/86 (2.33%)  2 2/161 (1.24%)  2
Infection with normal ANC, Anal/perianal * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Infection with normal ANC, Bladder (urinary) * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Infection with normal ANC, Blood * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Infection with normal ANC, Bone (Osteomyelitis) * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Infection with normal ANC, Colon * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Infection with normal ANC, Kidney * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Infection with normal ANC, Lung (Pneumonia) * 1  1/207 (0.48%)  1 2/209 (0.96%)  2 0/86 (0.00%)  0 2/161 (1.24%)  2
Infection with normal ANC, Mediastinum NOS * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Infection with normal ANC, Scrotum * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Infection with normal ANC, Soft tissue NOS * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Infection with normal ANC, Upper airway NOS * 1  2/207 (0.97%)  2 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Infection with normal ANC, Urinary tract NOS * 1  0/207 (0.00%)  0 1/209 (0.48%)  1 0/86 (0.00%)  0 0/161 (0.00%)  0
Infection with normal ANC, Wound * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  1 0/161 (0.00%)  0
Infection with unknown ANC, Abdomen NOS * 1  0/207 (0.00%)  0 1/209 (0.48%)  1 0/86 (0.00%)  0 0/161 (0.00%)  0
Infection with unknown ANC, Appendix * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Infection with unknown ANC, Bladder (urinary) * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Infection with unknown ANC, Blood * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Infection with unknown ANC, Bronchus * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Infection with unknown ANC, Lung (Pneumonia) * 1  1/207 (0.48%)  1 1/209 (0.48%)  1 1/86 (1.16%)  1 3/161 (1.86%)  3
Infection with unknown ANC, Pleura (Empyema) * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Infection with unknown ANC, Prostate * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  1 0/161 (0.00%)  0
Opportunistic infection * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Injury, poisoning and procedural complications         
Intraop injury, Artery-aorta * 1  1/207 (0.48%)  2 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Intraop injury, Bone * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Intraop injury, Meninges * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Intraop injury, Neck NOS * 1  0/207 (0.00%)  0 1/209 (0.48%)  1 0/86 (0.00%)  0 0/161 (0.00%)  0
Intraop injury, Thyroid * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  1 1/161 (0.62%)  1
Intraop injury, Trachea * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Metabolism and nutrition disorders         
Amylase * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Creatinine * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Hypercalcemia * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  1 1/161 (0.62%)  1
Hyperglycemia * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Hypocalcemia * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Hypomagnesemia * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Hyponatremia * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Metabolic/Lab - Other * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Musculoskeletal and connective tissue disorders         
Arthritis * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Extremity - upper (Function) * 1  0/207 (0.00%)  0 1/209 (0.48%)  3 0/86 (0.00%)  0 1/161 (0.62%)  1
Fracture * 1  4/207 (1.93%)  4 6/209 (2.87%)  6 2/86 (2.33%)  2 4/161 (2.48%)  4
Lumbar spine ROM * 1  1/207 (0.48%)  2 0/209 (0.00%)  0 1/86 (1.16%)  1 1/161 (0.62%)  1
Muscle weakness, Extremity - lower * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Muscle weakness, Extremity - upper * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Muscle weakness, Whole body/generalized * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  1 1/161 (0.62%)  1
Musculoskeletal - Other * 1  4/207 (1.93%)  5 3/209 (1.44%)  3 5/86 (5.81%)  6 4/161 (2.48%)  4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Secondary malignancy (possibly related to cancer treatment) * 1  11/207 (5.31%)  13 6/209 (2.87%)  6 4/86 (4.65%)  4 3/161 (1.86%)  3
Nervous system disorders         
CNS ischemia * 1  3/207 (1.45%)  3 1/209 (0.48%)  1 0/86 (0.00%)  0 2/161 (1.24%)  2
CSF leak * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  1 0/161 (0.00%)  0
Cognitive disturbance * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 1/86 (1.16%)  1 0/161 (0.00%)  0
Encephalopathy * 1  0/207 (0.00%)  0 1/209 (0.48%)  1 0/86 (0.00%)  0 0/161 (0.00%)  0
Laryngeal nerve * 1  0/207 (0.00%)  0 1/209 (0.48%)  1 0/86 (0.00%)  0 0/161 (0.00%)  0
Mood Alteration, Anxiety * 1  0/207 (0.00%)  0 1/209 (0.48%)  1 0/86 (0.00%)  0 0/161 (0.00%)  0
Mood alteration, Depression * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Neurology - Other * 1  1/207 (0.48%)  1 2/209 (0.96%)  2 1/86 (1.16%)  1 1/161 (0.62%)  1
Neuropathy: Cranial, CN II Vision * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Neuropathy: motor * 1  0/207 (0.00%)  0 3/209 (1.44%)  3 0/86 (0.00%)  0 1/161 (0.62%)  1
Neuropathy: sensory * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  2 1/161 (0.62%)  1
Seizure * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Syncope (Fainting) * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Renal and urinary disorders         
Renal - Other * 1  3/207 (1.45%)  4 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Urinary retention * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Reproductive system and breast disorders         
Sexual - Other * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 2/161 (1.24%)  2
Respiratory, thoracic and mediastinal disorders         
Airway obstruction, Larynx * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Airway obstruction, Pharynx * 1  0/207 (0.00%)  0 1/209 (0.48%)  1 0/86 (0.00%)  0 0/161 (0.00%)  0
Airway obstruction, Trachea * 1  3/207 (1.45%)  3 3/209 (1.44%)  4 0/86 (0.00%)  0 1/161 (0.62%)  1
Atelectasis * 1  0/207 (0.00%)  0 1/209 (0.48%)  1 0/86 (0.00%)  0 0/161 (0.00%)  0
Dyspnea (Shortness of breath) * 1  8/207 (3.86%)  9 7/209 (3.35%)  8 2/86 (2.33%)  2 8/161 (4.97%)  11
Hypoxia * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Pleural effusion * 1  6/207 (2.90%)  8 4/209 (1.91%)  4 9/86 (10.47%)  13 5/161 (3.11%)  5
Pneumonitis * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  2 2/161 (1.24%)  4
Pneumothorax * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 2/161 (1.24%)  2
Pulmonary - Other * 1  1/207 (0.48%)  1 1/209 (0.48%)  1 0/86 (0.00%)  0 2/161 (1.24%)  2
Skin and subcutaneous tissue disorders         
Dermatology - Other * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 2/161 (1.24%)  2
Hand-foot skin reaction * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Rash/desquamation * 1  2/207 (0.97%)  3 0/209 (0.00%)  0 0/86 (0.00%)  0 3/161 (1.86%)  3
Ulceration * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Wound complication, non-infectious * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Vascular disorders         
CNS hemorrhage * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Hematoma * 1  0/207 (0.00%)  0 1/209 (0.48%)  1 0/86 (0.00%)  0 0/161 (0.00%)  0
Hemorrhage - Other * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Hemorrhage pulmonary, Bronchopulmonary NOS * 1  0/207 (0.00%)  0 2/209 (0.96%)  2 0/86 (0.00%)  0 0/161 (0.00%)  0
Hemorrhage pulmonary, Bronchus * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Hemorrhage pulmonary, Larynx * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Hemorrhage pulmonary, Lung * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  1 3/161 (1.86%)  4
Hemorrhage pulmonary, Respiratory tract NOS * 1  0/207 (0.00%)  0 1/209 (0.48%)  1 0/86 (0.00%)  0 0/161 (0.00%)  0
Hemorrhage, GI, Anus * 1  1/207 (0.48%)  1 1/209 (0.48%)  1 0/86 (0.00%)  0 0/161 (0.00%)  0
Hemorrhage, GI, Colon * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 1/86 (1.16%)  3 0/161 (0.00%)  0
Hemorrhage, GI, Varices (rectal) * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Hemorrhage, GU, Urinary NOS * 1  0/207 (0.00%)  0 0/209 (0.00%)  0 0/86 (0.00%)  0 1/161 (0.62%)  1
Hemorrhage, GU, Uterus * 1  0/207 (0.00%)  0 1/209 (0.48%)  1 0/86 (0.00%)  0 0/161 (0.00%)  0
Thrombosis/Embolism (vascular access) * 1  1/207 (0.48%)  1 0/209 (0.00%)  0 0/86 (0.00%)  0 0/161 (0.00%)  0
Thrombosis/Thrombus/Embolism * 1  1/207 (0.48%)  1 4/209 (1.91%)  4 2/86 (2.33%)  4 1/161 (0.62%)  1
Vascular - Other * 1  0/207 (0.00%)  0 1/209 (0.48%)  1 1/86 (1.16%)  3 0/161 (0.00%)  0
1
Term from vocabulary, MedDRA (20.0)
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Sorafenib (Double Blind Only) Placebo (Double Blind Only) Sorafenib, Open Label Only (Sorafenib Continued) Placebo, Open Label Only (Switch to Sorafenib)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   202/207 (97.58%)      173/209 (82.78%)      74/86 (86.05%)      159/161 (98.76%)    
Blood and lymphatic system disorders         
Blood - Other * 1  6/207 (2.90%)  6 6/209 (2.87%)  10 6/86 (6.98%)  20 10/161 (6.21%)  23
Edema: Limb * 1  13/207 (6.28%)  17 6/209 (2.87%)  7 8/86 (9.30%)  9 8/161 (4.97%)  11
Hemoglobin * 1  18/207 (8.70%)  24 10/209 (4.78%)  11 8/86 (9.30%)  9 26/161 (16.15%)  32
Leukocytes * 1  9/207 (4.35%)  13 4/209 (1.91%)  8 5/86 (5.81%)  6 8/161 (4.97%)  15
Lymphopenia * 1  7/207 (3.38%)  7 6/209 (2.87%)  8 1/86 (1.16%)  1 10/161 (6.21%)  13
Platelets * 1  8/207 (3.86%)  12 2/209 (0.96%)  2 3/86 (3.49%)  4 11/161 (6.83%)  15
Cardiac disorders         
Hypertension * 1  85/207 (41.06%)  103 28/209 (13.40%)  35 10/86 (11.63%)  13 51/161 (31.68%)  57
Gastrointestinal disorders         
Anorexia * 1  67/207 (32.37%)  89 12/209 (5.74%)  12 7/86 (8.14%)  9 48/161 (29.81%)  52
Constipation * 1  32/207 (15.46%)  38 18/209 (8.61%)  19 4/86 (4.65%)  4 27/161 (16.77%)  29
Diarrhea * 1  142/207 (68.60%)  226 32/209 (15.31%)  40 22/86 (25.58%)  26 96/161 (59.63%)  165
Dry mouth * 1  16/207 (7.73%)  16 8/209 (3.83%)  8 2/86 (2.33%)  2 7/161 (4.35%)  7
Dysphagia * 1  14/207 (6.76%)  17 9/209 (4.31%)  9 5/86 (5.81%)  7 12/161 (7.45%)  14
GI - Other * 1  9/207 (4.35%)  11 4/209 (1.91%)  4 2/86 (2.33%)  3 10/161 (6.21%)  11
Heartburn * 1  10/207 (4.83%)  11 10/209 (4.78%)  10 1/86 (1.16%)  1 13/161 (8.07%)  14
Mucositis (functional/symptomatic), Oral cavity * 1  49/207 (23.67%)  58 7/209 (3.35%)  7 6/86 (6.98%)  14 41/161 (25.47%)  49
Nausea * 1  43/207 (20.77%)  55 25/209 (11.96%)  29 10/86 (11.63%)  12 52/161 (32.30%)  56
Taste Alteration * 1  16/207 (7.73%)  16 0/209 (0.00%)  0 1/86 (1.16%)  1 11/161 (6.83%)  12
Vomiting * 1  23/207 (11.11%)  36 13/209 (6.22%)  14 3/86 (3.49%)  3 18/161 (11.18%)  25
General disorders         
Fatigue * 1  102/207 (49.28%)  132 52/209 (24.88%)  58 19/86 (22.09%)  23 68/161 (42.24%)  87
Fever * 1  22/207 (10.63%)  30 10/209 (4.78%)  11 8/86 (9.30%)  10 21/161 (13.04%)  26
Flu-like syndrome * 1  18/207 (8.70%)  32 10/209 (4.78%)  14 4/86 (4.65%)  5 11/161 (6.83%)  14
Insomnia * 1  14/207 (6.76%)  16 6/209 (2.87%)  6 5/86 (5.81%)  5 16/161 (9.94%)  17
Pain, Abdomen NOS * 1  30/207 (14.49%)  42 10/209 (4.78%)  10 6/86 (6.98%)  7 30/161 (18.63%)  38
Pain, Back * 1  24/207 (11.59%)  28 21/209 (10.05%)  24 10/86 (11.63%)  11 15/161 (9.32%)  19
Pain, Bone * 1  14/207 (6.76%)  21 18/209 (8.61%)  22 7/86 (8.14%)  12 12/161 (7.45%)  13
Pain, Chest wall * 1  6/207 (2.90%)  8 3/209 (1.44%)  3 2/86 (2.33%)  2 9/161 (5.59%)  9
Pain, Chest/Thorax NOS * 1  16/207 (7.73%)  20 5/209 (2.39%)  5 1/86 (1.16%)  1 17/161 (10.56%)  18
Pain, Dental/Teeth/peridontal * 1  11/207 (5.31%)  15 4/209 (1.91%)  4 2/86 (2.33%)  2 11/161 (6.83%)  16
Pain, Extremity - limb * 1  31/207 (14.98%)  49 19/209 (9.09%)  27 3/86 (3.49%)  3 28/161 (17.39%)  43
Pain, Head/Headache * 1  38/207 (18.36%)  48 16/209 (7.66%)  17 3/86 (3.49%)  3 24/161 (14.91%)  29
Pain, Joint * 1  20/207 (9.66%)  23 14/209 (6.70%)  19 5/86 (5.81%)  7 19/161 (11.80%)  25
Pain, Muscle * 1  19/207 (9.18%)  23 15/209 (7.18%)  17 6/86 (6.98%)  6 11/161 (6.83%)  17
Pain, Neck * 1  9/207 (4.35%)  10 6/209 (2.87%)  6 1/86 (1.16%)  1 9/161 (5.59%)  9
Pain, Oral cavity * 1  7/207 (3.38%)  7 2/209 (0.96%)  2 0/86 (0.00%)  0 9/161 (5.59%)  11
Pain, Other * 1  24/207 (11.59%)  30 16/209 (7.66%)  17 8/86 (9.30%)  13 27/161 (16.77%)  31
Pain, Throat/Pharynx/Larynx * 1  21/207 (10.14%)  26 9/209 (4.31%)  11 1/86 (1.16%)  3 19/161 (11.80%)  24
Weight loss * 1  102/207 (49.28%)  114 29/209 (13.88%)  30 29/86 (33.72%)  33 75/161 (46.58%)  85
Immune system disorders         
Rhinitis * 1  9/207 (4.35%)  11 7/209 (3.35%)  10 2/86 (2.33%)  2 9/161 (5.59%)  10
Infections and infestations         
Infection - Other * 1  22/207 (10.63%)  29 12/209 (5.74%)  19 8/86 (9.30%)  11 12/161 (7.45%)  17
Metabolism and nutrition disorders         
ALT * 1  26/207 (12.56%)  29 9/209 (4.31%)  10 0/86 (0.00%)  0 15/161 (9.32%)  19
AST * 1  23/207 (11.11%)  26 5/209 (2.39%)  6 1/86 (1.16%)  2 11/161 (6.83%)  14
Hypoalbuminemia * 1  2/207 (0.97%)  3 4/209 (1.91%)  4 5/86 (5.81%)  7 7/161 (4.35%)  7
Hypocalcemia * 1  38/207 (18.36%)  54 11/209 (5.26%)  13 12/86 (13.95%)  21 30/161 (18.63%)  47
Hypokalemia * 1  14/207 (6.76%)  21 5/209 (2.39%)  6 4/86 (4.65%)  6 14/161 (8.70%)  17
Hypophosphatemia * 1  7/207 (3.38%)  11 1/209 (0.48%)  1 0/86 (0.00%)  0 11/161 (6.83%)  12
Metabolic/Lab - Other * 1  79/207 (38.16%)  123 37/209 (17.70%)  50 21/86 (24.42%)  34 56/161 (34.78%)  101
Musculoskeletal and connective tissue disorders         
Musculoskeletal - Other * 1  19/207 (9.18%)  21 9/209 (4.31%)  9 7/86 (8.14%)  10 11/161 (6.83%)  16
Nervous system disorders         
Dizziness * 1  14/207 (6.76%)  17 7/209 (3.35%)  8 1/86 (1.16%)  1 12/161 (7.45%)  13
Mood Alteration, Anxiety * 1  7/207 (3.38%)  8 6/209 (2.87%)  6 0/86 (0.00%)  0 9/161 (5.59%)  10
Neuropathy: sensory * 1  32/207 (15.46%)  42 13/209 (6.22%)  16 5/86 (5.81%)  6 21/161 (13.04%)  26
Respiratory, thoracic and mediastinal disorders         
Cough * 1  34/207 (16.43%)  43 34/209 (16.27%)  39 9/86 (10.47%)  10 23/161 (14.29%)  28
Dyspnea (Shortness of breath) * 1  31/207 (14.98%)  36 27/209 (12.92%)  32 10/86 (11.63%)  14 25/161 (15.53%)  32
Pulmonary - Other * 1  7/207 (3.38%)  8 7/209 (3.35%)  7 7/86 (8.14%)  11 7/161 (4.35%)  9
Voice changes * 1  25/207 (12.08%)  33 6/209 (2.87%)  6 2/86 (2.33%)  2 12/161 (7.45%)  13
Skin and subcutaneous tissue disorders         
Alopecia * 1  141/207 (68.12%)  155 18/209 (8.61%)  18 4/86 (4.65%)  4 96/161 (59.63%)  103
Dermatology - Other * 1  30/207 (14.49%)  56 6/209 (2.87%)  8 12/86 (13.95%)  14 31/161 (19.25%)  43
Dry skin * 1  30/207 (14.49%)  36 12/209 (5.74%)  14 6/86 (6.98%)  7 17/161 (10.56%)  17
Hand-foot skin reaction * 1  158/207 (76.33%)  223 20/209 (9.57%)  24 13/86 (15.12%)  15 109/161 (67.70%)  136
Pruritus * 1  44/207 (21.26%)  52 22/209 (10.53%)  24 3/86 (3.49%)  6 21/161 (13.04%)  25
Rash/desquamation * 1  107/207 (51.69%)  166 25/209 (11.96%)  29 9/86 (10.47%)  10 67/161 (41.61%)  94
Vascular disorders         
Hemorrhage pulmonary, Nose * 1  15/207 (7.25%)  17 2/209 (0.96%)  3 2/86 (2.33%)  2 8/161 (4.97%)  11
1
Term from vocabulary, MedDRA (20.0)
*
Indicates events were collected by non-systematic assessment
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.
The investigator must discuss any publication with the sponsor prior to release and obtain written consent of the sponsor on the intended publication. He/she must send a draft manuscript of the publication 30 days in advance of submission in order to obtain approval prior to submission of the final version for publication. In case of a difference of opinion, the contents will be discussed in order to find a solution which satisfies both parties.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Therapeutic Area Head
Organization: BAYER
EMail: clinical-trials-contact@bayer.com
Layout table for additonal information
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00984282     History of Changes
Other Study ID Numbers: 14295
2009-012007-25 ( EudraCT Number )
First Submitted: September 24, 2009
First Posted: September 25, 2009
Results First Submitted: August 19, 2013
Results First Posted: December 10, 2013
Last Update Posted: September 13, 2018