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A Randomized, Double-Blinded, Placebo-Controlled Study of Sorafenib in Patients With Advanced Hepatocellular Carcinoma

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ClinicalTrials.gov Identifier: NCT00492752
Recruitment Status : Completed
First Posted : June 27, 2007
Results First Posted : January 13, 2011
Last Update Posted : April 16, 2014
Sponsor:
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Carcinoma, Hepatocellular
Interventions Drug: Sorafenib (Nexavar, BAY43-9006)
Drug: Placebo
Enrollment 226
Recruitment Details Subjects with advanced hepatocellular carcinoma were enrolled from 12 Oct 2005 to 26 Jan 2007 at 23 centers in China (15 centers), Taiwan (5 centers), and Korea (3 centers).
Pre-assignment Details 271 subjects were enrolled in a 28-day screening period; 226 subjects were randomized either to Sorafenib or placebo (2:1 ratio) (intent-to-treat [ITT] population: for efficacy analysis); 224 subjects received at least one dose of study drug (safety population: for safety analysis). Majority of screen failures did not meet the inclusion criteria.
Arm/Group Title A1) Sorafenib (Nexavar, BAY43-9006) - no Open Label Phase A2) Sorafenib (Nexavar, BAY43-9006) - With Open Label Phase B1) Placebo - no Open Label Phase B2) Placebo First - Then Open Label Sorafenib Treatment Phase
Hide Arm/Group Description

Participants randomized to Sorafenib treatment until unblinding (August 19, 2007), Sorafenib administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.

Note: Safety Data of participants in the arm presented here are part of the data reported in Reporting Group (RG) 1.

Participants randomized to Sorafenib treatment from until unblinding (August 19, 2007) until end of trial (July 27, 2009), Sorafenib administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.

Note: Safety Data of participants in the arm presented here are part of the data reported in Reporting Group (RG) 1.

Participants randomized to Sorafenib-matching Placebo until unblinding (August 19, 2007), Placebo tablets matching in appearance were orally administered twice daily (bid).

Note: Safety Data of participants in the arm presented here are part of the data reported in Reporting Group (RG) 2.

Participants switched to Open-label Sorafenib treatment from Placebo after unblinding (August 19, 2007), Sorafenib administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.

Note: Safety Data of participants in the arm presented here are the data reported in Reporting Group (RG) 3.

Period Title: Double Blind Treatment
Started 134 16 70 6
Received Treatment 133 [1] 16 [2] 69 [3] 6 [2]
Completed 120 16 67 6
Not Completed 14 0 3 0
Reason Not Completed
Death             13             0             2             0
Adverse Event             1             0             0             0
Protocol Violation             0             0             1             0
[1]
Safety Population. 1 participant never received treatment due to an Adverse Event.
[2]
Safety Population
[3]
Safety Population. 1 participant never received treatment due to protocol violation.
Period Title: Follow-up and/or Open Label Sorafenib
Started 120 16 67 6
Follow-up Only (no Open Label Treatment) 120 0 67 0
Follow-up First, Then Open Label 0 16 0 6
Completed 34 [1] 0 20 [2] 0
Not Completed 86 16 47 6
Reason Not Completed
Adverse Event             0             2             0             2
Death             75             5             45             1
Lost to Follow-up             8             1             2             0
Withdrawal by Subject             2             1             0             0
Progression by clinical judgement             0             1             0             2
Radiological and clinical progression             0             0             0             1
Switch to commercial drug             0             6             0             0
Progression measurement proven             1             0             0             0
[1]
1 participant completed all assessments, 33 were followed up until the end of this trial
[2]
20 participants were followed up until the end of this trial
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo Total
Hide Arm/Group Description Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment. Placebo tablets matching in appearance were orally administered bid (twice daily). Total of all reporting groups
Overall Number of Baseline Participants 150 76 226
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 150 participants 76 participants 226 participants
51
(23 to 86)
52
(25 to 79)
51
(23 to 86)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 150 participants 76 participants 226 participants
<65 years 131 63 194
>=65 years 19 13 32
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 150 participants 76 participants 226 participants
Female
127
  84.7%
66
  86.8%
193
  85.4%
Male
23
  15.3%
10
  13.2%
33
  14.6%
Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 150 participants 76 participants 226 participants
0 33 22 55
1 108 50 158
2 9 4 13
[1]
Measure Description: Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) is a scale (range 0 [fully active] to 5 [dead]) that measures how cancer affects a patient. Subjects entering this study were to have an ECOG score of 0, 1 (restricted in physically strenuous activity but ambulatory), or 2 (capable of all self care but cannot carry out work activities.
Tumor burden   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 150 participants 76 participants 226 participants
Absent 32 15 47
Present 118 61 179
[1]
Measure Description: Tumor burden refers to the number of cancer cells, the size of a tumor, or the amount of cancer in the body, and is called the tumor load. Randomization was stratified by “tumor burden” assessment ie, the presence of either macroscopic vascular invasion as determined by radiological assessment and/or extra hepatic spread versus none.
1.Primary Outcome
Title Overall Survival
Hide Description Overall Survival (OS) was defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.
Time Frame From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
In this study the overall survival was measured for the ITT population from the date of randomization until the date of death due to any cause. For patients alive or lost to follow-up at the time of analysis, time to death was to be censored at their last date of follow-up, or at the data cut-off of 09 Aug 2007 (23 months after randomization).
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Hide Arm/Group Description:
Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.
Placebo tablets matching in appearance were orally administered bid (twice daily).
Overall Number of Participants Analyzed 150 76
Median (95% Confidence Interval)
Unit of Measure: days
198
(169 to 230)
127
(114 to 166)
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 0.014144
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.6783
Confidence Interval 95%
0.4962 to 0.9272
Estimation Comments Hazard ratio is for Sorafenib vs placebo.
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 0.003464
Comments [Not Specified]
Method Log Rank
Comments log rank test stratified by country, tumor burden, and ECOG.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.6208
Confidence Interval 95%
0.4498 to 0.8568
Estimation Comments Hazard ratio is for Sorafenib vs placebo
2.Secondary Outcome
Title Time to Symptomatic Progression (TTSP)
Hide Description Time to Symptomatic Progression (TTSP) was defined as the time from date of randomization to symptomatic progression. Subjects without symptomatic progression at the time of analysis were censored at their last date of tumor evaluation.
Time Frame From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Time to Symptomatic Progression was measured for the ITT population (all randomized subjects) up to the data cut-off date of of 09 Aug 2007 (23 months after randomization)
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Hide Arm/Group Description:
Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.
Placebo tablets matching in appearance were orally administered bid (twice daily).
Overall Number of Participants Analyzed 150 76
Median (95% Confidence Interval)
Unit of Measure: days
105
(85 to 129)
103
(73 to 124)
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 0.497537
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.9032
Confidence Interval 95%
0.6705 to 1.2165
Estimation Comments Hazard ratio is for Sorafenib vs placebo.
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 0.437926
Comments [Not Specified]
Method Log Rank
Comments log rank test stratified by country, tumor burden, and ECOG.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.8831
Confidence Interval 95%
0.6449 to 1.2093
Estimation Comments Hazard ratio is for Sorafenib vs placebo
3.Secondary Outcome
Title Time to Progression (TTP)
Hide Description Time to progression (TTP) was defined as the time from date of randomization to radiologically documented disease progression. Subjects without progression at the time of analysis were censored at their last date of tumor evaluation。
Time Frame From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Time to progression was measured for the ITT population (all randomized subjects) up to the data cut-off date of 09 Aug 2007 (23 months after randomization).
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Hide Arm/Group Description:
Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.
Placebo tablets matching in appearance were orally administered bid (twice daily).
Overall Number of Participants Analyzed 150 76
Median (95% Confidence Interval)
Unit of Measure: days
84
(80 to 109)
41.5
(41 to 47)
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 0.000537
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.5744
Confidence Interval 95%
0.4154 to 0.7942
Estimation Comments Hazard ratio is for Sorafenib vs placebo
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 0.000540
Comments [Not Specified]
Method Log Rank
Comments log rank test stratified by country, tumor burden, and ECOG.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.5375
Confidence Interval 95%
0.3763 to 0.7677
Estimation Comments Hazard ratio is for Sorafenib vs placebo
4.Secondary Outcome
Title Disease Control
Hide Description Disease Control (DC) was defined as the total number of subjects whose best response was not Progressive Disease (PD: an increase in the sum of tumor lesions sizes) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR: disappearance of tumor lesions) + total number of Partial Response (PR: a decrease of at least 30% in the sum of tumor lesion sizes) + total number of Stable Disease (SD: steady state of disease); CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating).
Time Frame From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Disease control rate was measured for the ITT population (all randomized subjects)
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Hide Arm/Group Description:
Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.
Placebo tablets matching in appearance were orally administered bid (twice daily).
Overall Number of Participants Analyzed 150 76
Measure Type: Number
Unit of Measure: participants
Yes 53 12
No 97 64
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sorafenib (Nexavar, BAY43-9006)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Disease control rate
Estimated Value 0.3533
Confidence Interval 95%
0.2771 to 0.4355
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Disease control rate
Estimated Value 0.1579
Confidence Interval 95%
0.0843 to 0.2596
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change in Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8) Score From Baseline to Cycle 1 and Cycle 3
Hide Description The FHSI-8 questionnaire was completed at baseline and every 3 weeks during treatment and at the end of treatment visit only for subjects who withdrew for reasons other than symptomatic progression. Patient reported outcome was measured using the FHSI-8 score changes from baseline throughout the study period. FHSI-8 assesses hepatobiliary cancer symptoms with total score ranges from 0 to 32 (0 = the best quality of life; 32 = the worst quality of life with severe symptoms)..
Time Frame Baseline up to Cycle 1 and Cycle 3. From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FHSI-8 score changes from baseline by visit were assessed for the ITT population.
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Hide Arm/Group Description:
Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.
Placebo tablets matching in appearance were orally administered bid (twice daily).
Overall Number of Participants Analyzed 150 76
Mean (Standard Deviation)
Unit of Measure: scores on a scale
cycle 1 26  (4.8) 26  (4.8)
cycle 3 24  (6.3) 25  (5.3)
6.Secondary Outcome
Title Change in Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) Score From Baseline to Cycle 3 and End of Treatment
Hide Description The FACT-Hep questionnaire was also completed to assess patient reported outcome. The FACT-Hep assesses hepatobiliary cancer-related quality of life. FACT-Hep total score ranges from 0 to 180 (0=All questions answered "Not at all"; 180=All questions answered "Very much").
Time Frame Baseline up to Cycle 3 and end of treatment. From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FACT-Hep score changes from baseline by visit were assessed for the ITT population.
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Hide Arm/Group Description:
Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.
Placebo tablets matching in appearance were orally administered bid (twice daily).
Overall Number of Participants Analyzed 150 76
Mean (Standard Deviation)
Unit of Measure: scores on a scale
cycle 3 -10  (25.5) -3  (19.9)
end of treatment -25  (27.2) -23  (31.3)
7.Secondary Outcome
Title Number of Participants With Different Tumor Response
Hide Description Tumor Response (= Best Overall Response) of a subject was defined as the best tumor response (confirmed Complete Response (CR: disappearance of tumor lesions), confirmed* Partial Response (PR: a decrease of at least 30% in the sum of tumor lesion sizes), Stable Disease (SD: steady state of disease), or Progressive Disease (PD: an increase in the sum of tumor lesions sizes)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
Time Frame From randomization/start of treatment of the first subject until approximately 23 months after randomization when the subjects on placebo were offered the option to crossover to sorafenib treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The tumor response was measured for the ITT population.
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Hide Arm/Group Description:
Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.
Placebo tablets matching in appearance were orally administered bid (twice daily).
Overall Number of Participants Analyzed 150 76
Measure Type: Number
Unit of Measure: participants
Complete Response (CR) 0 0
Partial Response (PR) 5 1
Stable Disease (SD) 81 21
Progressive Disease (PD) 46 41
Not assessable 18 13
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 0.67
Comments [Not Specified]
Method Fisher Exact
Comments based on tumor response rate (CR+PR)
8.Secondary Outcome
Title Duration of Response
Hide Description Duration of Response was defined as the time from date of first response (Complete Response (CR) or Partial Response (PR)) to the date when Progressive Disease (PD) is first documented, or to the date of death, whichever occurs first. Subjects still having CR or PR at the time of analysis were censored at their last tumor assessment.
Time Frame From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The duration of response was measured for the ITT population.
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Hide Arm/Group Description:
Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.
Placebo tablets matching in appearance were orally administered bid (twice daily).
Overall Number of Participants Analyzed 5 1
Median (Full Range)
Unit of Measure: days
210
(82 to 343)
252
(252 to 252)
9.Secondary Outcome
Title Time to Response
Hide Description Time to Response (TTR) for subjects who achieved a response (Complete Response (CR) or Partial Response (PR) ) was defined as the time from date of randomization to the earliest date that the response was first documented.
Time Frame From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The time to response was measured for the ITT population.
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Hide Arm/Group Description:
Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.
Placebo tablets matching in appearance were orally administered bid (twice daily).
Overall Number of Participants Analyzed 5 1
Median (Full Range)
Unit of Measure: days
84
(45 to 126)
42
(42 to 42)
10.Secondary Outcome
Title Area Under the Curve From Time 0 to 12 Hours Post-dose (AUC 0-12) After 21 Days of Sorafenib Treatment
Hide Description The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. A plot of concentration vs time after dosing is created, and the area under this curve is calculated by standard methods (eg, trapezoidal rule) to provide a measure of how much drug was in the bloodstream following dosing.
Time Frame PK assessments made at following times: pre-dose, 1 h, 2h, 4h, 8h,and 12h after at least 21 consecutive doses during Cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The stated goal in the protocol was to obtain PK data from approximately 39 patients. As this was only descriptive information, the sample size was not critical. All patients who provided PK data were included in the analysis.
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Hide Arm/Group Description:
Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.
Placebo tablets matching in appearance were orally administered bid (twice daily).
Overall Number of Participants Analyzed 24 0
Geometric Mean (Full Range)
Unit of Measure: mg*h/L
35.7
(7.8 to 149.2)
11.Secondary Outcome
Title Normalized Area Under the Curve (AUC Norm) After 21 Days of Sorafenib Treatment
Hide Description The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. A plot of concentration vs time after dosing is created, and the area under this curve is calculated by standard methods (eg, trapezoidal rule) to provide a measure of how much drug was in the bloodstream following dosing.
Time Frame PK assessments made at following times: pre-dose, 1 h, 2h, 4h, 8h,and 12h after at least 21 consecutive doses during Cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The stated goal in the protocol was to obtain PK data from approximately 39 patients. As this was only descriptive information, the sample size was not critical. All patients who provided PK data were included in the analysis.
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Hide Arm/Group Description:
Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.
Placebo tablets matching in appearance were orally administered bid (twice daily).
Overall Number of Participants Analyzed 24 0
Geometric Mean (Full Range)
Unit of Measure: g*h/L
6.6
(1.3 to 21.6)
12.Secondary Outcome
Title Maximum Concentration (Cmax) After 21 Days of Sorafenib Treatment
Hide Description Cmax refers to the highest plasma concentration of drug reached after dosing. It is obtained by collecting a series of blood samples after dosing, and analyzing them for drug content by a sensitive and specific analytical method. The highest measured concentration is referred to as the Cmax.
Time Frame PK assessments made at following times: pre-dose, 1 h, 2h, 4h, 8h,and 12h after at least 21 consecutive doses during Cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The stated goal in the protocol was to obtain PK data from approximately 39 patients. As this was only descriptive information, the sample size was not critical. All patients who provided PK data were included in the analysis.
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Hide Arm/Group Description:
Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.
Placebo tablets matching in appearance were orally administered bid (twice daily).
Overall Number of Participants Analyzed 24 0
Geometric Mean (Full Range)
Unit of Measure: mg/L
4.44
(1.121 to 16.7)
13.Secondary Outcome
Title Normalized Maximum Concentration (Cmaxnorm) After 21 Days of Sorafenib Treatment
Hide Description Cmaxnorm refers to the maximum plasma concentration of Sorafenib corrected for dose and body weight (Cmaxnorm = Cmax/(mg/kg)).
Time Frame PK assessments made at following times: pre-dose, 1 h, 2h, 4h, 8h,and 12h after at least 21 consecutive doses during Cycle 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The stated goal in the protocol was to obtain PK data from approximately 39 patients. As this was only descriptive information, the sample size was not critical. All patients who provided PK data were included in the analysis.
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Hide Arm/Group Description:
Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.
Placebo tablets matching in appearance were orally administered bid (twice daily).
Overall Number of Participants Analyzed 24 0
Geometric Mean (Full Range)
Unit of Measure: g/mL
0.66
(0.18 to 2.43)
14.Secondary Outcome
Title Time of Maximum Concentration (Tmax) After 21 Days of Sorafenib Treatment
Hide Description Tmax refers to the time after dosing when a drug attains its maximum concentration in the blood. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content. The time corresponding to the highest measurable concentration (Cmax) is referred to as Tmax.
Time Frame PK assessments made at following times: pre-dose, 1 h, 2h, 4h, 8h,and 12h after at least 21 consecutive doses during Cycle 1
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Hide Analysis Population Description
The stated goal in the protocol was to obtain PK data from approximately 39 patients. As this was only descriptive information, the sample size was not critical. All patients who provided PK data were included in the analysis.
Arm/Group Title Sorafenib (Nexavar, BAY43-9006) Placebo
Hide Arm/Group Description:
Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.
Placebo tablets matching in appearance were orally administered bid (twice daily).
Overall Number of Participants Analyzed 24 0
Median (Full Range)
Unit of Measure: hours
4.0
(0.5 to 12)
Time Frame Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009).
Adverse Event Reporting Description Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
 
Arm/Group Title Sorafenib, All (Double-Blind and Open Label Phase) Placebo, All (Double-Blind and Open Label Phase) Placebo, Open Label Only (Participants Switched to Sorafenib)
Hide Arm/Group Description Reporting Group 1 (RG 1): All participants randomized to Sorafenib treatment (data from start of treatment until end of trial [July 27, 2009]). Sorafenib administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment. Reporting Group 2 (RG 2): All participants randomized to Sorafenib-matching Placebo (data from start of treatment until end of trial [July 27, 2009]). Treatment for Double-Blind phase (before unblinding [August 19, 2007]): Placebo tablets matching in appearance were orally administered twice daily (bid); Treatment for Open Label phase (after unblinding [August 19, 2007]): Sorafenib administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment. Reporting Group 3 (RG 3): Participants switched to Open-label Sorafenib treatment from Placebo ( Data after unblinding [August 19, 2007] until end of this trial [July 27, 2009]). Sorafenib administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.
All-Cause Mortality
Sorafenib, All (Double-Blind and Open Label Phase) Placebo, All (Double-Blind and Open Label Phase) Placebo, Open Label Only (Participants Switched to Sorafenib)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Sorafenib, All (Double-Blind and Open Label Phase) Placebo, All (Double-Blind and Open Label Phase) Placebo, Open Label Only (Participants Switched to Sorafenib)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   76/149 (51.01%)   34/75 (45.33%)   3/6 (50.00%) 
Blood and lymphatic system disorders       
Edema: Limb * 1  2/149 (1.34%)  0/75 (0.00%)  0/6 (0.00%) 
Cardiac disorders       
Hypertension * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Cardiac General - Other * 1  0/149 (0.00%)  1/75 (1.33%)  0/6 (0.00%) 
Gastrointestinal disorders       
Anorexia * 1  2/149 (1.34%)  0/75 (0.00%)  0/6 (0.00%) 
Ascites * 1  7/149 (4.70%)  3/75 (4.00%)  0/6 (0.00%) 
Colitis * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Diarrhea * 1  4/149 (2.68%)  0/75 (0.00%)  0/6 (0.00%) 
Distension * 1  2/149 (1.34%)  2/75 (2.67%)  0/6 (0.00%) 
Dysphagia * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Mucositis (Functional/Symptomatic), Oral Cavity * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Nausea * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Ileus * 1  0/149 (0.00%)  1/75 (1.33%)  0/6 (0.00%) 
GI - Other * 1  2/149 (1.34%)  1/75 (1.33%)  0/6 (0.00%) 
Stricture, GI, Biliary Tree * 1  2/149 (1.34%)  0/75 (0.00%)  0/6 (0.00%) 
Vomiting * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
General disorders       
Death Not Associated With CTCAE Term, Disease Progression NOS * 1  22/149 (14.77%)  8/75 (10.67%)  1/6 (16.67%) 
Death Not Associated With CTCAE Term, Multi - Organ Failure * 1  3/149 (2.01%)  3/75 (4.00%)  1/6 (16.67%) 
Death Not Associated With CTCAE Term, Sudden Death * 1  3/149 (2.01%)  1/75 (1.33%)  0/6 (0.00%) 
Fever * 1  5/149 (3.36%)  3/75 (4.00%)  0/6 (0.00%) 
Fatigue * 1  2/149 (1.34%)  1/75 (1.33%)  0/6 (0.00%) 
Constitutional Symptoms - Other * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Rigors / Chills * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Pain, Back * 1  1/149 (0.67%)  1/75 (1.33%)  0/6 (0.00%) 
Pain, Chest Wall * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Pain, Tumor Pain * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Pain, Abdomen NOS * 1  7/149 (4.70%)  3/75 (4.00%)  0/6 (0.00%) 
Pain, Bone * 1  0/149 (0.00%)  1/75 (1.33%)  0/6 (0.00%) 
Pain, Other * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Pain, Pelvis * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Hepatobiliary disorders       
Liver Dysfunction * 1  6/149 (4.03%)  8/75 (10.67%)  0/6 (0.00%) 
Hepatobiliary - Other * 1  1/149 (0.67%)  1/75 (1.33%)  0/6 (0.00%) 
Infections and infestations       
Febrile Neutropenia * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Infection - Other * 1  2/149 (1.34%)  1/75 (1.33%)  0/6 (0.00%) 
Infection With Unknown ANC, Biliary Tree * 1  0/149 (0.00%)  1/75 (1.33%)  0/6 (0.00%) 
Infection With Unknown ANC, Lung (Pneumonia) * 1  4/149 (2.68%)  1/75 (1.33%)  0/6 (0.00%) 
Infection With Unknown ANC, Wound * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Metabolism and nutrition disorders       
Bilirubin (Hyperbilirubinemia) * 1  3/149 (2.01%)  1/75 (1.33%)  0/6 (0.00%) 
Hypoglycemia * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Hypokalemia * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Metabolic / Lab - Other * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Musculoskeletal and connective tissue disorders       
Fracture * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Secondary Malignancy (Possibly Related to Cancer Treatment) * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Nervous system disorders       
CNS Ischemia * 1  2/149 (1.34%)  0/75 (0.00%)  0/6 (0.00%) 
Encephalopathy * 1  1/149 (0.67%)  3/75 (4.00%)  0/6 (0.00%) 
Neuropathy: Motor * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Neurology - Other * 1  1/149 (0.67%)  0/75 (0.00%)  1/6 (16.67%) 
Seizure * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Syncope (Fainting) * 1  0/149 (0.00%)  1/75 (1.33%)  0/6 (0.00%) 
Renal and urinary disorders       
Renal Failure * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Renal - Other * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Aspiration * 1  0/149 (0.00%)  1/75 (1.33%)  0/6 (0.00%) 
Pulmonary - Other * 1  3/149 (2.01%)  1/75 (1.33%)  0/6 (0.00%) 
Pneumothorax * 1  0/149 (0.00%)  0/75 (0.00%)  1/6 (16.67%) 
Dyspnea (Shortness of Breath) * 1  4/149 (2.68%)  1/75 (1.33%)  0/6 (0.00%) 
Skin and subcutaneous tissue disorders       
Hand-Foot Skin Reaction * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Vascular disorders       
CNS Hemorrhage * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Hemorrhage, GI, Abdomen NOS * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Hemorrhage, GI, Anus * 1  0/149 (0.00%)  1/75 (1.33%)  0/6 (0.00%) 
Hemorrhage, GI, Varices (Esophageal) * 1  4/149 (2.68%)  1/75 (1.33%)  0/6 (0.00%) 
Hemorrhage, GI, Stomach * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Hemorrhage, GI, Liver * 1  0/149 (0.00%)  1/75 (1.33%)  0/6 (0.00%) 
Hemorrhage, GI, Upper GI NOS * 1  9/149 (6.04%)  4/75 (5.33%)  0/6 (0.00%) 
Hemorrhage - Other * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Hemorrhage Pulmonary, Nose * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
Hemorrhage Pulmonary, Respiratory Tract NOS * 1  0/149 (0.00%)  1/75 (1.33%)  0/6 (0.00%) 
Thrombosis/Thrombus/Embolism * 1  1/149 (0.67%)  0/75 (0.00%)  0/6 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, NCI-CTCAE v. 3.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Sorafenib, All (Double-Blind and Open Label Phase) Placebo, All (Double-Blind and Open Label Phase) Placebo, Open Label Only (Participants Switched to Sorafenib)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   144/149 (96.64%)   65/75 (86.67%)   4/6 (66.67%) 
Blood and lymphatic system disorders       
Blood - Other * 1  8/149 (5.37%)  1/75 (1.33%)  0/6 (0.00%) 
Hemoglobin * 1  29/149 (19.46%)  10/75 (13.33%)  0/6 (0.00%) 
Leukocytes * 1  18/149 (12.08%)  4/75 (5.33%)  0/6 (0.00%) 
Platelets * 1  35/149 (23.49%)  10/75 (13.33%)  1/6 (16.67%) 
PTT * 1  12/149 (8.05%)  4/75 (5.33%)  0/6 (0.00%) 
Edema: Limb * 1  10/149 (6.71%)  8/75 (10.67%)  0/6 (0.00%) 
Cardiac disorders       
Hypertension * 1  33/149 (22.15%)  4/75 (5.33%)  0/6 (0.00%) 
Ear and labyrinth disorders       
Tinnitus * 1  12/149 (8.05%)  0/75 (0.00%)  0/6 (0.00%) 
Endocrine disorders       
Hypothyroidism * 1  0/149 (0.00%)  0/75 (0.00%)  1/6 (16.67%) 
Eye disorders       
Cataract * 1  1/149 (0.67%)  0/75 (0.00%)  1/6 (16.67%) 
Optic Disc Edema * 1  0/149 (0.00%)  0/75 (0.00%)  1/6 (16.67%) 
Gastrointestinal disorders       
Anorexia * 1  46/149 (30.87%)  13/75 (17.33%)  0/6 (0.00%) 
Ascites * 1  41/149 (27.52%)  13/75 (17.33%)  0/6 (0.00%) 
Constipation * 1  20/149 (13.42%)  12/75 (16.00%)  0/6 (0.00%) 
Diarrhea * 1  64/149 (42.95%)  12/75 (16.00%)  3/6 (50.00%) 
Distension * 1  24/149 (16.11%)  15/75 (20.00%)  0/6 (0.00%) 
GI - Other * 1  10/149 (6.71%)  1/75 (1.33%)  0/6 (0.00%) 
Mucositis (Clinical Exam), Oral Cavity * 1  6/149 (4.03%)  2/75 (2.67%)  1/6 (16.67%) 
Nausea * 1  37/149 (24.83%)  19/75 (25.33%)  0/6 (0.00%) 
Vomiting * 1  25/149 (16.78%)  13/75 (17.33%)  0/6 (0.00%) 
General disorders       
Fatigue * 1  51/149 (34.23%)  15/75 (20.00%)  0/6 (0.00%) 
Fever * 1  38/149 (25.50%)  8/75 (10.67%)  0/6 (0.00%) 
Insomnia * 1  25/149 (16.78%)  17/75 (22.67%)  0/6 (0.00%) 
Weight Loss * 1  62/149 (41.61%)  13/75 (17.33%)  0/6 (0.00%) 
Pain, Abdomen NOS * 1  54/149 (36.24%)  16/75 (21.33%)  0/6 (0.00%) 
Pain, Back * 1  23/149 (15.44%)  9/75 (12.00%)  0/6 (0.00%) 
Pain, Chest Wall * 1  12/149 (8.05%)  2/75 (2.67%)  0/6 (0.00%) 
Pain, Chest/Thorax NOS * 1  1/149 (0.67%)  2/75 (2.67%)  1/6 (16.67%) 
Pain, Dental/Teeth/Peridontal * 1  1/149 (0.67%)  0/75 (0.00%)  1/6 (16.67%) 
Pain, Head/Headache * 1  12/149 (8.05%)  1/75 (1.33%)  1/6 (16.67%) 
Pain, Joint * 1  6/149 (4.03%)  0/75 (0.00%)  1/6 (16.67%) 
Pain, Liver * 1  10/149 (6.71%)  9/75 (12.00%)  0/6 (0.00%) 
Pain, Muscle * 1  10/149 (6.71%)  1/75 (1.33%)  0/6 (0.00%) 
Pain, Other * 1  11/149 (7.38%)  2/75 (2.67%)  0/6 (0.00%) 
Pain, Stomach * 1  3/149 (2.01%)  4/75 (5.33%)  0/6 (0.00%) 
Pain, Throat/Pharynx/Larynx * 1  10/149 (6.71%)  1/75 (1.33%)  1/6 (16.67%) 
Flu - Like Syndrome * 1  3/149 (2.01%)  1/75 (1.33%)  1/6 (16.67%) 
Pain, Bone * 1  8/149 (5.37%)  5/75 (6.67%)  0/6 (0.00%) 
Hepatobiliary disorders       
Hepatobiliary - Other * 1  8/149 (5.37%)  6/75 (8.00%)  0/6 (0.00%) 
Immune system disorders       
Allergic Reaction * 1  2/149 (1.34%)  4/75 (5.33%)  0/6 (0.00%) 
Infections and infestations       
Infection - Other * 1  10/149 (6.71%)  6/75 (8.00%)  0/6 (0.00%) 
Metabolism and nutrition disorders       
Alkaline Phosphatase * 1  39/149 (26.17%)  14/75 (18.67%)  0/6 (0.00%) 
ALT * 1  49/149 (32.89%)  18/75 (24.00%)  2/6 (33.33%) 
Amylase * 1  8/149 (5.37%)  0/75 (0.00%)  0/6 (0.00%) 
AST * 1  63/149 (42.28%)  23/75 (30.67%)  1/6 (16.67%) 
Bilirubin (Hyperbilirubinemia) * 1  56/149 (37.58%)  24/75 (32.00%)  2/6 (33.33%) 
Creatinine * 1  10/149 (6.71%)  3/75 (4.00%)  0/6 (0.00%) 
GGT * 1  9/149 (6.04%)  7/75 (9.33%)  0/6 (0.00%) 
Hyperglycemia * 1  8/149 (5.37%)  7/75 (9.33%)  0/6 (0.00%) 
Hyperkalemia * 1  7/149 (4.70%)  5/75 (6.67%)  0/6 (0.00%) 
Hyperuricemia * 1  10/149 (6.71%)  6/75 (8.00%)  0/6 (0.00%) 
Hypoalbuminemia * 1  34/149 (22.82%)  16/75 (21.33%)  0/6 (0.00%) 
Hypocalcemia * 1  12/149 (8.05%)  3/75 (4.00%)  0/6 (0.00%) 
Hypokalemia * 1  11/149 (7.38%)  2/75 (2.67%)  0/6 (0.00%) 
Hyponatremia * 1  23/149 (15.44%)  10/75 (13.33%)  0/6 (0.00%) 
Hypophosphatemia * 1  17/149 (11.41%)  4/75 (5.33%)  1/6 (16.67%) 
Lipase * 1  19/149 (12.75%)  4/75 (5.33%)  0/6 (0.00%) 
Metabolic / Lab - Other * 1  33/149 (22.15%)  9/75 (12.00%)  0/6 (0.00%) 
Nervous system disorders       
Dizziness * 1  4/149 (2.68%)  5/75 (6.67%)  1/6 (16.67%) 
Memory Impairment * 1  0/149 (0.00%)  0/75 (0.00%)  1/6 (16.67%) 
Respiratory, thoracic and mediastinal disorders       
Cough * 1  29/149 (19.46%)  12/75 (16.00%)  2/6 (33.33%) 
Dyspnea (Shortness of Breath) * 1  17/149 (11.41%)  12/75 (16.00%)  0/6 (0.00%) 
Pulmonary - Other * 1  11/149 (7.38%)  7/75 (9.33%)  0/6 (0.00%) 
Skin and subcutaneous tissue disorders       
Alopecia * 1  40/149 (26.85%)  1/75 (1.33%)  0/6 (0.00%) 
Dermatology - Other * 1  15/149 (10.07%)  3/75 (4.00%)  0/6 (0.00%) 
Hand - Foot Skin Reaction * 1  69/149 (46.31%)  2/75 (2.67%)  2/6 (33.33%) 
Pruritus * 1  19/149 (12.75%)  9/75 (12.00%)  0/6 (0.00%) 
Rash / Desquamation * 1  33/149 (22.15%)  7/75 (9.33%)  0/6 (0.00%) 
Vascular disorders       
Hemorrhage Pulmonary, Respiratory Tract NOS * 1  2/149 (1.34%)  1/75 (1.33%)  1/6 (16.67%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, NCI-CTCAE v. 3.0
On review of unblinded data, up to 19 Mar. 2007, the independent Data Monitoring Committee concluded the efficacy results can be considered positive, recommended subjects under placebo to cross over to Sorafenib; study continued to extension phase.
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 send a draft manuscript to be submitted for publication or to be presented or abstract to Bayer at least 60 days in advance of submission in order to obtain approval prior to submission of the final version for publication or presentation. In case of a difference of opinion between Bayer and the Investigator(s), the contents of the publication will be discussed in order to find a solution, which satisfies both parties.
Results Point of Contact
Name/Title: Therapeutic Area Head
Organization: BAYER
Phone: <not disclosed>
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00492752     History of Changes
Other Study ID Numbers: 11849
First Submitted: June 26, 2007
First Posted: June 27, 2007
Results First Submitted: December 8, 2010
Results First Posted: January 13, 2011
Last Update Posted: April 16, 2014