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BAY43-9006 (Sorafenib) Versus Interferon Alpha-2a in Patients With Unresectable and/or Metastatic Renal Cell Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00117637
Recruitment Status : Completed
First Posted : July 8, 2005
Results First Posted : December 15, 2010
Last Update Posted : October 31, 2014
Sponsor:
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Carcinoma, Renal Cell
Interventions Drug: Sorafenib (Nexavar, BAY43-9006)
Drug: Interferon
Enrollment 189
Recruitment Details The start of enrollment was 14 June 2005 and the last day of enrollment was 12 September 2005.
Pre-assignment Details All 189 (97 Sorafenib/92 Interferon) randomized subjects were included in the intent to treat (ITT) population, and 187 (97 Sorafenib/90 Interferon) were included in the safety population according to the protocol, which defined eligibility for safety analyses by the prerequisite that a patient had received at least one dose of study medication.
Arm/Group Title First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Hide Arm/Group Description Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis. Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Period Title: First Intervention (Period 1)
Started 97 92
Subjects Received Treatment 97 90
Completed 79 67
Not Completed 18 25
Reason Not Completed
Adverse Event             11             16
Lost to Follow-up             0             2
Protocol Violation             1             0
Withdrawal by Subject             2             4
study terminated by the sponsor             3             1
protocol driven decision point             1             0
investig. decision, not protocol driven             0             1
reason not reported             0             1
Period Title: Second Intervention (Period 2)
Started 49 [1] 61 [1]
Subjects Received Treatment 49 61
Completed 39 39
Not Completed 10 22
Reason Not Completed
Adverse Event             0             9
Lost to Follow-up             1             0
Protocol Violation             1             0
Withdrawal by Subject             4             3
study terminated by the sponsor             2             9
non compliant with study medication             1             1
reason not reported             1             0
[1]
Not all patients who completed Period 1 (first progression) enter into Period 2
Arm/Group Title First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg Total
Hide Arm/Group Description Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis. Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]). Total of all reporting groups
Overall Number of Baseline Participants 97 92 189
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 97 participants 92 participants 189 participants
62
(34 to 78)
62.5
(18 to 80)
62
(18 to 80)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 97 participants 92 participants 189 participants
Female
32
  33.0%
40
  43.5%
72
  38.1%
Male
65
  67.0%
52
  56.5%
117
  61.9%
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 97 participants 92 participants 189 participants
0 56 49 105
1 41 43 84
[1]
Measure Description: Category 0 = Fully active, able to carry on all pre-diseases performance without restriction; Category 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (e.g. light housework, office work).
Motzer risk factors   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 97 participants 92 participants 189 participants
low 52 47 99
intermediate 44 44 88
high 1 0 1
missing 0 1 1
[1]
Measure Description: Definition according to Motzer's score (predictive factor): low = no risk factor available; intermediate = 1 or 2 risk factors available; high = 3 or more risk factors available.
Race  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 97 participants 92 participants 189 participants
White 68 75 143
Asian 0 1 1
Missing 29 16 45
Renal Cell Carcinoma (RCC) subtype  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 97 participants 92 participants 189 participants
clear cell 85 81 166
other variant 12 11 23
Time since first progression  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 97 participants 92 participants 189 participants
0.2
(0 to 4.5)
0.2
(0 to 12.4)
0.2
(0 to 12.4)
Time since initial diagnosis  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 97 participants 92 participants 189 participants
0.9
(0.1 to 13.7)
1
(0.1 to 20.2)
1
(0.1 to 20.2)
1.Primary Outcome
Title Progression-free Survival (PFS) Based on Independent Radiological Review for the First Intervention Period
Hide Description Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression (radiological or clinical or death due to any cause, whichever occurs first). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation
Time Frame From randomization of the first subject until 15 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 97 92
Median (95% Confidence Interval)
Unit of Measure: months
5.7
(5.0 to 7.4)
5.6
(3.7 to 7.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg, First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Comments The study was planned to show a 80% improvement in PFS for the group treated with Sorafenib compared to the group treated with Interferon, with a 80% power and a 2-sided type I error of 5%
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.50
Comments The log rank test is stratified by region (western Europe, Eastern Europe, USA) and by Motzer risk category (low, intermediate).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.61 to 1.27
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Progression-free Survival (PFS) Based on Investigator Assessment for the First Intervention Period
Hide Description Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression (radiological or clinical or death due to any cause, whichever occurs first). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation
Time Frame From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 97 92
Median (95% Confidence Interval)
Unit of Measure: months
5.6
(5.4 to 7.5)
7.0
(5.4 to 8.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg, First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Comments The study was planned to show a 80% improvement in PFS for the group treated with Sorafenib compared to the group treated with Interferon, with a 80% power and a 2-sided type I error of 5%
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.469
Comments The log rank test is stratified by region (western Europe, Eastern Europe, USA) and by Motzer risk category (low, intermediate).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.882
Confidence Interval (2-Sided) 95%
0.628 to 1.239
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Disease Control (DC) According to Independent Central Review for the First Intervention Period
Hide Description Disease Control (DC) was defined as the total number of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD); CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating). CR: disappearance of tumor lesions (TL); PR: a decrease of at least 30% in the sum of TL sizes; SD: steady state of disease; PD: an increase of at least 20% in the sum of TL sizes.
Time Frame From randomization of the first subject until 15 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 97 92
Measure Type: Number
Unit of Measure: participants
disease control (CR or PR or SD) 77 59
no disease control 10 24
Unknown 10 9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg, First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments The Cochran-Mantel-Haenszel statistics was stratified by region and Motzer risk category.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
4.Secondary Outcome
Title Disease Control (DC) According to the Investigator Assessment for the First Intervention Period
Hide Description Disease Control (DC) was defined as the total number of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD); CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating). CR: disappearance of tumor lesions (TL); PR: a decrease of at least 30% in the sum of TL sizes; SD: steady state of disease; PD: an increase of at least 20% in the sum of TL sizes.
Time Frame From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 97 92
Measure Type: Number
Unit of Measure: participants
disease control (CR or PR or SD) 83 62
no disease control 7 24
Unknown 7 6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg, First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments the Cochran-Mantel-Haenszel statistics was stratified by region and Motzer risk category.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
5.Secondary Outcome
Title Disease Control (DC) According to the Investigator Assessment for the Second Intervention Period
Hide Description Disease Control (DC) was defined as the total number of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD); CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating). CR: disappearance of tumor lesions (TL); PR: a decrease of at least 30% in the sum of TL sizes; SD: steady state of disease; PD: an increase of at least 20% in the sum of TL sizes.
Time Frame From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 49 61
Measure Type: Number
Unit of Measure: participants
disease control (CR or PR or SD) 25 49
no disease control 16 6
Unknown 8 6
6.Secondary Outcome
Title Analysis of the Quality of Life by Use of the Respiratory Domain of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) After Intervention for the First Intervention Period
Hide Description The FKSI questionnaire comprises 15 questions dispatched within 4 domains (respiratory, pain, general symptoms and overall Quality of Life (QoL)) plus 2 individual items. Each question was answered on a five point scale from 0 (not at all) to 4 (very much) indicating the severity of symptoms. The total score range was from 0 to 60 with higher scores indicating subjects reported fewer kidney cancer related symptoms and concerns. The respiratory domain of the FKSI comprises 2 questions:" I have been short in breath" and "I have been coughing"; its score ranges from 0 to 8.
Time Frame From randomization of the first subject until 15 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
Arm/Group Title Sorafenib 400 mg in Period 1 Interferon Therapy in Period 1
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 91 87
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
6.4
(3.3 to 9.6)
5.1
(0.8 to 9.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sorafenib 400 mg in Period 1, Interferon Therapy in Period 1
Comments The least square (LS) means have been adjusted according to the stratification factors (geographical region, Motzer score at baseline) and using the baseline respiratory score as covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.022
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
7.Secondary Outcome
Title Analysis of the Quality of Life by Use of the Respiratory Domain of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the Second Intervention Period
Hide Description The FKSI questionnaire comprises 15 questions dispatched within 4 domains (respiratory, pain, general symptoms and overall Quality of Life (QoL)) plus 2 individual items. Each question was answered on a five point scale from 0 (not at all) to 4 (very much) indicating the severity of symptoms. The total score range was from 0 to 60 with higher scores indicating subjects reported fewer kidney cancer related symptoms and concerns. The respiratory domain of the FKSI comprises 2 questions:" I have been short in breath" and "I have been coughing"; its score ranges from 0 to 8.
Time Frame From randomization of the first subject until 15 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
Arm/Group Title Sorafenib 600 mg (as Dose Escalation After 400 mg) Sorafenib 400 mg (After Interferon Therapy)
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 37 42
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
5.7
(-8.2 to 19.7)
6.4
(-1.2 to 14)
8.Secondary Outcome
Title Analysis of the Quality of Life by Use of Total Score of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the First Intervention Period
Hide Description The FKSI questionnaire comprises 15 questions dispatched within 4 domains (respiratory, pain, general symptoms and overall Quality of Life (QoL)) plus 2 individual items. Each question was answered on a five point scale from 0 (not at all) to 4 (very much) indicating the severity of symptoms. The total score range was from 0 to 60 with higher scores indicating subjects reported fewer kidney cancer related symptoms and concerns.
Time Frame From randomization of the first subject until 15 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
Arm/Group Title Sorafenib 400 mg in Period 1 Interferon Therapy in Period 1
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 90 86
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
40.5
(15.9 to 65.1)
34.6
(4.4 to 64.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sorafenib 400 mg in Period 1, Interferon Therapy in Period 1
Comments The least square (LS) means have been adjusted according to the stratification factors (geographical region, Motzer score at baseline) and using the baseline respiratory score as covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
9.Secondary Outcome
Title Analysis of the Quality of Life by Use of Total Score of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the Second Intervention Period
Hide Description The FKSI questionnaire comprises 15 questions dispatched within 4 domains (respiratory, pain, general symptoms and overall Quality of Life (QoL)) plus 2 individual items. Each question was answered on a five point scale from 0 (not at all) to 4 (very much) indicating the severity of symptoms. The total score range was from 0 to 60 with higher scores indicating subjects reported fewer kidney cancer related symptoms and concerns.
Time Frame From randomization of the first subject until 15 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
Arm/Group Title Sorafenib 600 mg (as Dose Escalation After 400 mg) Sorafenib 400 mg (After Interferon Therapy)
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 37 42
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
34.6
(6.3 to 62.9)
42.3
(9.5 to 75.2)
10.Secondary Outcome
Title Analysis of the Quality of Life (QoL) by Use of Functional Assessment of Cancer Therapy-Biologic-response Modifiers (FACT-BRM) for the First Intervention Period
Hide Description The FACT-BRM comprises 40 questions within 6 domains (physical well being, social/family well being, emotional well being, additional concern: physical, and additional concern: emotional). Each question was answered on a five point scale from 0 (not at all) to 4 (very much). The total score range is from 0 to 160 with higher scores indicating better QoL.
Time Frame From randomization of the first subject until 15 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
Arm/Group Title Sorafenib 400 mg in Period 1 Interferon Therapy in Period 1
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 89 86
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
104
(29 to 179)
93
(-9 to 195)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sorafenib 400 mg in Period 1, Interferon Therapy in Period 1
Comments The least square (LS) means have been adjusted according to the stratification factors (geographical region, Motzer score at baseline).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.073
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
11.Secondary Outcome
Title Analysis of the Quality of Life (QoL) by Use of Functional Assessment of Cancer Therapy-Biologic-response Modifiers (FACT-BRM) for the Second Intervention Period
Hide Description The FACT-BRM comprises 40 questions within 6 domains (physical well being, social/family well being, emotional well being, additional concern: physical, and additional concern: emotional). Each question was answered on a five point scale from 0 (not at all) to 4 (very much). The total score range is from 0 to 160 with higher scores indicating better QoL.
Time Frame From randomization of the first subject until 15 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
Arm/Group Title Sorafenib 600 mg (as Dose Escalation After 400 mg) Sorafenib 400 mg (After Interferon Therapy)
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 37 40
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
89.7
(18.2 to 161.1)
108.4
(17.6 to 199.2)
12.Secondary Outcome
Title Analysis of the Treatment Tolerability (Effectiveness) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period
Hide Description The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
Time Frame From randomization of the first subject until 15 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
Arm/Group Title Sorafenib 400 mg in Period 1 Interferon Therapy in Period 1
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 29 34
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
52
(44 to 61)
42
(34 to 50)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sorafenib 400 mg in Period 1, Interferon Therapy in Period 1
Comments The least square (LS) means have been adjusted according to the stratification factors (geographical region, Motzer score at baseline).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.067
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
13.Secondary Outcome
Title Analysis of the Treatment Tolerability (Side Effects) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period
Hide Description The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
Time Frame From randomization of the first subject until 15 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
Arm/Group Title Sorafenib 400 mg in Period 1 Interferon Therapy in Period 1
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 27 30
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
63
(54 to 72)
46
(37 to 54)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sorafenib 400 mg in Period 1, Interferon Therapy in Period 1
Comments The least square (LS) means have been adjusted according to the stratification factors (geographical region, Motzer score at baseline).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
14.Secondary Outcome
Title Analysis of the Treatment Tolerability (Convenience) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period
Hide Description The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
Time Frame From randomization of the first subject until 15 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
Arm/Group Title Sorafenib 400 mg in Period 1 Interferon Therapy in Period 1
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 30 33
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
82
(75 to 89)
66
(60 to 73)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sorafenib 400 mg in Period 1, Interferon Therapy in Period 1
Comments The least square (LS) means have been adjusted according to the stratification factors (geographical region, Motzer score at baseline).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
15.Secondary Outcome
Title Analysis of the Treatment Tolerability (Global Satisfaction) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period
Hide Description The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
Time Frame From randomization of the first subject until 15 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
Arm/Group Title Sorafenib 400 mg in Period 1 Interferon Therapy in Period 1
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 30 33
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
60
(51 to 70)
46
(37 to 55)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sorafenib 400 mg in Period 1, Interferon Therapy in Period 1
Comments The least square (LS) means have been adjusted according to the stratification factors (geographical region, Motzer score at baseline).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
16.Secondary Outcome
Title Analysis of the Treatment Tolerability (Effectiveness) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period
Hide Description The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
Time Frame From randomization of the first subject until 15 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
Arm/Group Title Sorafenib 600 mg (as Dose Escalation After 400 mg) Sorafenib 400 mg (After Interferon Therapy)
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 10 9
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
56.9
(40.6 to 73.1)
40.3
(22.1 to 58.5)
17.Secondary Outcome
Title Analysis of the Treatment Tolerability (Side Effects) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period
Hide Description The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
Time Frame From randomization of the first subject until 15 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
Arm/Group Title Sorafenib 600 mg (as Dose Escalation After 400 mg) Sorafenib 400 mg (After Interferon Therapy)
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 10 8
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
61.3
(43.2 to 79.3)
57.6
(37.4 to 77.8)
18.Secondary Outcome
Title Analysis of the Treatment Tolerability (Convenience) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period
Hide Description The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
Time Frame From randomization of the first subject until 15 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
Arm/Group Title Sorafenib 600 mg (as Dose Escalation After 400 mg) Sorafenib 400 mg (After Interferon Therapy)
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 11 9
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
86.5
(74.7 to 98.3)
82.5
(68.9 to 96.1)
19.Secondary Outcome
Title Analysis of the Treatment Tolerability (Global Satisfaction) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period
Hide Description The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
Time Frame From randomization of the first subject until 15 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
Arm/Group Title Sorafenib 600 mg (as Dose Escalation After 400 mg) Sorafenib 400 mg (After Interferon Therapy)
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 11 8
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
39.9
(17.1 to 62.7)
35.4
(9.4 to 61.8)
20.Secondary Outcome
Title Tumor Response According to the Independent Radiological Review for the First Intervention Period
Hide Description Tumor Response (= Best Overall Response) of a subject was defined as the best tumor response (confirmed Complete Response (CR), confirmed Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes.
Time Frame From randomization of the first subject until 15 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 97 92
Measure Type: Number
Unit of Measure: participants
Complete Response (CR) 0 1
Partial Response (PR) 5 7
Stable Disease (SD) 72 51
Progressive Disease (PD) 10 24
Not Evaluated 10 9
21.Secondary Outcome
Title Tumor Response According to the Investigator Assessment for the First Intervention Period
Hide Description Tumor Response (= Best Overall Response) of a subject was defined as the best tumor response (confirmed Complete Response (CR), confirmed Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes
Time Frame From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 97 92
Measure Type: Number
Unit of Measure: participants
Complete Response (CR) 0 1
Partial Response (PR) 21 13
Stable Disease (SD) 62 48
Progressive Disease (PD) 7 24
Not Evaluated 7 6
22.Secondary Outcome
Title Tumor Response According to the Investigator Assessment for the Second Intervention Period
Hide Description Tumor Response (= Best Overall Response) of a subject was defined as the best tumor response (confirmed Complete Response (CR), confirmed Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes
Time Frame From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 49 61
Measure Type: Number
Unit of Measure: participants
Complete Response (CR) 0 1
Partial Response (PR) 0 11
Stable Disease (SD) 25 37
Progressive Disease (PD) 16 6
Not Evaluated 8 6
23.Secondary Outcome
Title Progression Free Survival According to the Investigator Assessment (Second Intervention Period)
Hide Description Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression (radiological or clinical or death due to any cause, whichever occurs first). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation
Time Frame From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 49 61
Median (95% Confidence Interval)
Unit of Measure: months
4.5
(2.4 to 6.5)
5.5
(3.8 to 7.1)
24.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall Survival 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 3 years and 9 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 97 92
Median (95% Confidence Interval)
Unit of Measure: months
14.8
(11.3 to 17.7)
26.9
(18.3 to 33.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg, First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
25.Secondary Outcome
Title Slope - Change in Trough Concentration/Cycle
Hide Description Plasma samples were collected prior to dosing every 4 weeks after the patient reached steady-state (at least 10 days at 400 mg BID (bis in die, twice daily)) to assess any potential trends in trough concentration over time.
Time Frame From start of treatment of the first subject until 15 months later assessed every 4 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who started on Sorafenib, not Interferon, and had been at the same dose (400 mg) for at least 10 days were considered valid for the analysis. Concentrations collected between 10-14 hours from the last dose were included in the analysis.
Arm/Group Title First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600mg
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Overall Number of Participants Analyzed 24
Mean (95% Confidence Interval)
Unit of Measure: 100*(mg/L/cycle)
-8.3
(-29.6 to 12.9)
26.Secondary Outcome
Title Average of All Trough Plasma Concentrations
Hide Description Plasma samples were collected prior to dosing every 4 weeks after the patient reached steady-state (at least 10 days at 400 mg BID).
Time Frame From start of treatment of the first subject until 15 months later assessed every 4 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who started on Sorafenib, not Interferon, and had been at the same dose (400 mg or 600 mg BID) for at least 10 days were considered valid for the analysis. Concentrations collected between 10-14 hours from the last dose were included in the analysis.
Arm/Group Title First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600mg
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Overall Number of Participants Analyzed 24
Geometric Mean (95% Confidence Interval)
Unit of Measure: 100*mg/L
93.9
(77.1 to 114.3)
27.Secondary Outcome
Title Duration of Response According to the Independent Radiological Review for the First Intervention Period
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 date of last contact
Time Frame From randomization of the first subject until 15 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 5 8
Median (Full Range)
Unit of Measure: months
7.5
(7.5 to 7.5)
7.7
(2.1 to 7.8)
28.Secondary Outcome
Title Duration of Response According to the Investigator Assessment for the First Intervention Period
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 date of last contact
Time Frame From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 21 14
Median (Full Range)
Unit of Measure: months
4.4
(1.2 to 22)
9.2
(1.5 to 19.7)
29.Secondary Outcome
Title Duration of Response According to the Investigator Assessment for the Second Intervention Period
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 date of last contact
Time Frame From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 0 12
Median (Full Range)
Unit of Measure: months
5.5
(1.1 to 16.7)
30.Secondary Outcome
Title Time to Response According to the Independent Radiological Review for the First Intervention Period
Hide Description Time to Response (TTR) for subjects who achieved a response (Complete Response (CR) or Partial Response (PR) with confirmation 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 15 months later, assessed every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 5 8
Median (Full Range)
Unit of Measure: months
1.8
(1.7 to 3.7)
5.4
(3.7 to 11)
31.Secondary Outcome
Title Time to Response According to the Investigator Assessment for the First Intervention Period
Hide Description Time to Response (TTR) for subjects who achieved a response (Complete Response (CR) or Partial Response (PR) with confirmation 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 3 years and 9 months later, assessed every 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 21 14
Median (Full Range)
Unit of Measure: months
3.5
(1.6 to 11.1)
5.4
(1.2 to 18.3)
32.Secondary Outcome
Title Time to Response According to the Investigator Assessment for the Second Intervention Period
Hide Description Time to Response (TTR) for subjects who achieved a response (Complete Response (CR) or Partial Response (PR) with confirmation) 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 3 years and 9 months later, assessed every 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 0 12
Median (Full Range)
Unit of Measure: months
1.7
(1.6 to 5.4)
33.Secondary Outcome
Title Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the First Intervention Period
Hide Description Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale that measures how cancer affects the daily life of a patient on an ordinal scale from grade 0 (best) to grade 5 (worst).
Time Frame From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
At the time of the analysis, only 95 subjects in Sorafenib 400 mg bid group and 89 in Interferon group were documented by study investigators due to various reasons (drop-out of patients by AEs, death etc.)
Arm/Group Title Sorafenib 400 mg in Period 1 Interferon Therapy in Period 1
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 95 89
Measure Type: Number
Unit of Measure: participants
0= Fully active without restriction 20 19
1= Restricted in physically strenuous activity 48 42
2= Ambulatory, capable of all selfcare 20 21
3= Capable of limited selfcare 5 5
4= Completely disabled 1 2
5= Dead 1 0
34.Secondary Outcome
Title Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the Second Intervention Period
Hide Description Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale that measures how cancer affects the daily life of a patient on an ordinal scale from grade 0 (best) to grade 5 (worst).
Time Frame From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
At the time of the analysis, only 45 subjects in Sorafenib 400/600 mg bid group and 58 in Interferon/Sorafenib 400 mg bid group were documented by study investigators due to various reasons (drop-out of patients by AEs, death etc.)
Arm/Group Title Sorafenib 600 mg (as Dose Escalation After 400 mg) Sorafenib 400 mg (After Interferon Therapy)
Hide Arm/Group Description:
Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis.
Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
Overall Number of Participants Analyzed 45 58
Measure Type: Number
Unit of Measure: participant s
0= Fully active without restriction 5 16
1= Restricted in physically strenuous activity 25 26
2= Ambulatory, capable of all selfcare 10 10
3= Capable of limited selfcare 4 5
4= Completely disabled 1 1
5= Dead 0 0
Time Frame [Not Specified]
Adverse Event Reporting Description Acronyms and abbreviations used: Common Terminology Criteria for Adverse Events (CTCAE); Not Otherwise Specified (NOS); Gastrointestinal (GI); Absolute Neutrophil Count (ANC); Alanine aminotransferase (ALT); Aspartate aminotransferase (AST); Central nervous system (CNS); Acute respiratory distress syndrome (ARDS)
 
Arm/Group Title Sorafenib 400 mg in Period 1 Interferon Therapy in Period 1 Sorafenib 600 mg (as Dose Escalation After 400 mg) Sorafenib 400 mg (After Interferon Therapy)
Hide Arm/Group Description Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis. Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]). Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months [median] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months [median]) on a continuous basis. Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months [median]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months [median]).
All-Cause Mortality
Sorafenib 400 mg in Period 1 Interferon Therapy in Period 1 Sorafenib 600 mg (as Dose Escalation After 400 mg) Sorafenib 400 mg (After Interferon Therapy)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Sorafenib 400 mg in Period 1 Interferon Therapy in Period 1 Sorafenib 600 mg (as Dose Escalation After 400 mg) Sorafenib 400 mg (After Interferon Therapy)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   47/97 (48.45%)   36/90 (40.00%)   14/49 (28.57%)   30/61 (49.18%) 
Blood and lymphatic system disorders         
hemoglobin * 1  2/97 (2.06%)  6/90 (6.67%)  2/49 (4.08%)  4/61 (6.56%) 
platelets * 1  0/97 (0.00%)  0/90 (0.00%)  1/49 (2.04%)  0/61 (0.00%) 
edema: limb * 1  0/97 (0.00%)  0/90 (0.00%)  1/49 (2.04%)  1/61 (1.64%) 
Cardiac disorders         
conduction abnormality, asystole * 1  0/97 (0.00%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
supraventricular arrhythmia, supraventricular arrhythmi * 1  0/97 (0.00%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
supraventricular arrhythmia, atrial fibrillation * 1  0/97 (0.00%)  0/90 (0.00%)  0/49 (0.00%)  1/61 (1.64%) 
cardiopulmonary arrest * 1  1/97 (1.03%)  0/90 (0.00%)  0/49 (0.00%)  0/61 (0.00%) 
cardiac ischemia / infarction * 1  1/97 (1.03%)  1/90 (1.11%)  0/49 (0.00%)  1/61 (1.64%) 
cardiac general - other * 1  1/97 (1.03%)  2/90 (2.22%)  1/49 (2.04%)  4/61 (6.56%) 
Ear and labyrinth disorders         
auditory / ear - other * 1  0/97 (0.00%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
Gastrointestinal disorders         
ascites * 1  0/97 (0.00%)  1/90 (1.11%)  0/49 (0.00%)  1/61 (1.64%) 
constipation * 1  0/97 (0.00%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
dehydration * 1  0/97 (0.00%)  1/90 (1.11%)  0/49 (0.00%)  1/61 (1.64%) 
diarrhea * 1  2/97 (2.06%)  0/90 (0.00%)  0/49 (0.00%)  2/61 (3.28%) 
nausea * 1  0/97 (0.00%)  2/90 (2.22%)  0/49 (0.00%)  1/61 (1.64%) 
obstruction, GI, stomach * 1  1/97 (1.03%)  0/90 (0.00%)  0/49 (0.00%)  0/61 (0.00%) 
perforation, GI, colon * 1  0/97 (0.00%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
vomiting * 1  2/97 (2.06%)  1/90 (1.11%)  1/49 (2.04%)  1/61 (1.64%) 
ileus * 1  0/97 (0.00%)  0/90 (0.00%)  0/49 (0.00%)  1/61 (1.64%) 
GI - other * 1  0/97 (0.00%)  0/90 (0.00%)  0/49 (0.00%)  1/61 (1.64%) 
General disorders         
death not associated with CTCAE term, death NOS * 1  1/97 (1.03%)  0/90 (0.00%)  0/49 (0.00%)  0/61 (0.00%) 
death not associated with CTCAE term, disease progress * 1  10/97 (10.31%)  1/90 (1.11%)  2/49 (4.08%)  7/61 (11.48%) 
fever * 1  1/97 (1.03%)  0/90 (0.00%)  0/49 (0.00%)  0/61 (0.00%) 
fatigue * 1  1/97 (1.03%)  3/90 (3.33%)  0/49 (0.00%)  2/61 (3.28%) 
constitutional symptoms - other * 1  6/97 (6.19%)  4/90 (4.44%)  0/49 (0.00%)  5/61 (8.20%) 
pain, back * 1  1/97 (1.03%)  0/90 (0.00%)  0/49 (0.00%)  0/61 (0.00%) 
pain, chest / thorax NOS * 1  1/97 (1.03%)  0/90 (0.00%)  0/49 (0.00%)  1/61 (1.64%) 
pain, extremity - limb * 1  0/97 (0.00%)  1/90 (1.11%)  1/49 (2.04%)  1/61 (1.64%) 
pain, tumor pain * 1  1/97 (1.03%)  0/90 (0.00%)  1/49 (2.04%)  0/61 (0.00%) 
pain, abdomen NOS * 1  3/97 (3.09%)  1/90 (1.11%)  0/49 (0.00%)  1/61 (1.64%) 
pain, head / headache * 1  1/97 (1.03%)  0/90 (0.00%)  0/49 (0.00%)  0/61 (0.00%) 
pain, bone * 1  2/97 (2.06%)  0/90 (0.00%)  1/49 (2.04%)  0/61 (0.00%) 
pain, other * 1  1/97 (1.03%)  0/90 (0.00%)  1/49 (2.04%)  1/61 (1.64%) 
pain, joint * 1  0/97 (0.00%)  0/90 (0.00%)  0/49 (0.00%)  1/61 (1.64%) 
Hepatobiliary disorders         
hepatobiliary - other * 1  0/97 (0.00%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
liver dysfunction * 1  0/97 (0.00%)  0/90 (0.00%)  0/49 (0.00%)  1/61 (1.64%) 
Immune system disorders         
allergic reaction * 1  1/97 (1.03%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
Infections and infestations         
infection (documented clinically), appendix * 1  0/97 (0.00%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
infection with normal ANC, abdomen NOS * 1  1/97 (1.03%)  0/90 (0.00%)  0/49 (0.00%)  0/61 (0.00%) 
infection with normal ANC, lung (pneumonia) * 1  1/97 (1.03%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
infection with unknown ANC, bronchus * 1  1/97 (1.03%)  0/90 (0.00%)  0/49 (0.00%)  0/61 (0.00%) 
infection with unknown ANC, upper airway NOS * 1  1/97 (1.03%)  0/90 (0.00%)  0/49 (0.00%)  0/61 (0.00%) 
infection (documented clinically), lung (pneumonia) * 1  0/97 (0.00%)  0/90 (0.00%)  1/49 (2.04%)  0/61 (0.00%) 
infection - other * 1  0/97 (0.00%)  0/90 (0.00%)  0/49 (0.00%)  3/61 (4.92%) 
Metabolism and nutrition disorders         
ALT * 1  0/97 (0.00%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
AST * 1  0/97 (0.00%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
bilirubin (hyperbilirubinemia) * 1  1/97 (1.03%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
hyperkalemia * 1  1/97 (1.03%)  0/90 (0.00%)  0/49 (0.00%)  0/61 (0.00%) 
hypocalcemia * 1  2/97 (2.06%)  0/90 (0.00%)  0/49 (0.00%)  0/61 (0.00%) 
hypoglycemia * 1  1/97 (1.03%)  0/90 (0.00%)  1/49 (2.04%)  0/61 (0.00%) 
metabolic / lab - other * 1  1/97 (1.03%)  2/90 (2.22%)  0/49 (0.00%)  0/61 (0.00%) 
Musculoskeletal and connective tissue disorders         
fracture * 1  0/97 (0.00%)  4/90 (4.44%)  0/49 (0.00%)  0/61 (0.00%) 
osteoporosis * 1  0/97 (0.00%)  0/90 (0.00%)  0/49 (0.00%)  1/61 (1.64%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
secondary malignancy (possibly related to cancer treat) * 1  1/97 (1.03%)  0/90 (0.00%)  0/49 (0.00%)  0/61 (0.00%) 
Nervous system disorders         
CNS ischemia * 1  1/97 (1.03%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
confusion * 1  0/97 (0.00%)  3/90 (3.33%)  0/49 (0.00%)  0/61 (0.00%) 
dizziness * 1  0/97 (0.00%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
hydrocephalus * 1  0/97 (0.00%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
mood alteration, depression * 1  0/97 (0.00%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
neurology - other * 1  1/97 (1.03%)  1/90 (1.11%)  0/49 (0.00%)  3/61 (4.92%) 
seizure * 1  2/97 (2.06%)  0/90 (0.00%)  0/49 (0.00%)  0/61 (0.00%) 
somnolence * 1  1/97 (1.03%)  0/90 (0.00%)  0/49 (0.00%)  0/61 (0.00%) 
speech impairment * 1  0/97 (0.00%)  0/90 (0.00%)  0/49 (0.00%)  1/61 (1.64%) 
Renal and urinary disorders         
renal failure * 1  3/97 (3.09%)  0/90 (0.00%)  0/49 (0.00%)  0/61 (0.00%) 
urinary retention * 1  1/97 (1.03%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
cough * 1  0/97 (0.00%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
pleural effusion * 1  3/97 (3.09%)  0/90 (0.00%)  0/49 (0.00%)  0/61 (0.00%) 
pneumonitis * 1  0/97 (0.00%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
pneumothorax * 1  0/97 (0.00%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
dyspnea (shortness of breath) * 1  2/97 (2.06%)  1/90 (1.11%)  1/49 (2.04%)  1/61 (1.64%) 
ARDS * 1  0/97 (0.00%)  0/90 (0.00%)  0/49 (0.00%)  1/61 (1.64%) 
airway obstruction, bronchus * 1  0/97 (0.00%)  0/90 (0.00%)  1/49 (2.04%)  0/61 (0.00%) 
pulmonary - other * 1  0/97 (0.00%)  0/90 (0.00%)  1/49 (2.04%)  3/61 (4.92%) 
Skin and subcutaneous tissue disorders         
hand-foot skin reaction * 1  2/97 (2.06%)  0/90 (0.00%)  0/49 (0.00%)  2/61 (3.28%) 
ulceration * 1  1/97 (1.03%)  0/90 (0.00%)  0/49 (0.00%)  0/61 (0.00%) 
Vascular disorders         
hematoma * 1  0/97 (0.00%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
hemorrhage, GI, colon * 1  0/97 (0.00%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
hemorrhage, GI, stomach * 1  0/97 (0.00%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
hemorrhage, GI, lower GI NOS * 1  0/97 (0.00%)  1/90 (1.11%)  0/49 (0.00%)  1/61 (1.64%) 
hemorrhage, GI, upper GI NOS * 1  0/97 (0.00%)  2/90 (2.22%)  0/49 (0.00%)  0/61 (0.00%) 
hemorrhage - other * 1  2/97 (2.06%)  0/90 (0.00%)  0/49 (0.00%)  0/61 (0.00%) 
hemorrhage pulmonary, bronchopulmonary NOS * 1  1/97 (1.03%)  0/90 (0.00%)  1/49 (2.04%)  0/61 (0.00%) 
hemorrhage, GI, anus * 1  0/97 (0.00%)  0/90 (0.00%)  1/49 (2.04%)  0/61 (0.00%) 
hemorrhage, GI, varices (rectal) * 1  0/97 (0.00%)  0/90 (0.00%)  1/49 (2.04%)  0/61 (0.00%) 
thrombosis / thrombus / embolism * 1  2/97 (2.06%)  0/90 (0.00%)  0/49 (0.00%)  1/61 (1.64%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, NCI-CTCAE v. 3.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Sorafenib 400 mg in Period 1 Interferon Therapy in Period 1 Sorafenib 600 mg (as Dose Escalation After 400 mg) Sorafenib 400 mg (After Interferon Therapy)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   93/97 (95.88%)   84/90 (93.33%)   40/49 (81.63%)   55/61 (90.16%) 
Blood and lymphatic system disorders         
neutrophils * 1  2/97 (2.06%)  13/90 (14.44%)  0/49 (0.00%)  0/61 (0.00%) 
hemoglobin * 1  14/97 (14.43%)  23/90 (25.56%)  10/49 (20.41%)  8/61 (13.11%) 
platelets * 1  1/97 (1.03%)  11/90 (12.22%)  2/49 (4.08%)  4/61 (6.56%) 
leukocytes * 1  2/97 (2.06%)  11/90 (12.22%)  0/49 (0.00%)  0/61 (0.00%) 
lymphopenia * 1  0/97 (0.00%)  0/90 (0.00%)  4/49 (8.16%)  3/61 (4.92%) 
edema: limb * 1  4/97 (4.12%)  5/90 (5.56%)  5/49 (10.20%)  2/61 (3.28%) 
Cardiac disorders         
hypertension * 1  24/97 (24.74%)  7/90 (7.78%)  1/49 (2.04%)  13/61 (21.31%) 
Gastrointestinal disorders         
anorexia * 1  34/97 (35.05%)  28/90 (31.11%)  11/49 (22.45%)  8/61 (13.11%) 
constipation * 1  12/97 (12.37%)  2/90 (2.22%)  3/49 (6.12%)  9/61 (14.75%) 
diarrhea * 1  54/97 (55.67%)  14/90 (15.56%)  12/49 (24.49%)  31/61 (50.82%) 
dry mouth * 1  5/97 (5.15%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
mucositis (functional / symptomatic), oral cavity * 1  12/97 (12.37%)  2/90 (2.22%)  1/49 (2.04%)  8/61 (13.11%) 
mucositis (clinical exam), oral cavity * 1  5/97 (5.15%)  1/90 (1.11%)  0/49 (0.00%)  4/61 (6.56%) 
nausea * 1  24/97 (24.74%)  26/90 (28.89%)  5/49 (10.20%)  14/61 (22.95%) 
taste alteration * 1  6/97 (6.19%)  6/90 (6.67%)  0/49 (0.00%)  0/61 (0.00%) 
vomiting * 1  18/97 (18.56%)  15/90 (16.67%)  5/49 (10.20%)  9/61 (14.75%) 
General disorders         
fever * 1  10/97 (10.31%)  30/90 (33.33%)  2/49 (4.08%)  4/61 (6.56%) 
insomnia * 1  2/97 (2.06%)  8/90 (8.89%)  0/49 (0.00%)  0/61 (0.00%) 
fatigue * 1  48/97 (49.48%)  41/90 (45.56%)  16/49 (32.65%)  22/61 (36.07%) 
weight loss * 1  26/97 (26.80%)  24/90 (26.67%)  12/49 (24.49%)  10/61 (16.39%) 
constitutional symptoms - other * 1  7/97 (7.22%)  11/90 (12.22%)  3/49 (6.12%)  4/61 (6.56%) 
rigors / chills * 1  1/97 (1.03%)  10/90 (11.11%)  0/49 (0.00%)  0/61 (0.00%) 
pain, back * 1  12/97 (12.37%)  5/90 (5.56%)  2/49 (4.08%)  4/61 (6.56%) 
pain, extremity - limb * 1  7/97 (7.22%)  7/90 (7.78%)  1/49 (2.04%)  7/61 (11.48%) 
pain, tumor pain * 1  4/97 (4.12%)  5/90 (5.56%)  0/49 (0.00%)  0/61 (0.00%) 
pain, abdomen NOS * 1  14/97 (14.43%)  10/90 (11.11%)  3/49 (6.12%)  7/61 (11.48%) 
pain, head / headache * 1  5/97 (5.15%)  13/90 (14.44%)  0/49 (0.00%)  5/61 (8.20%) 
pain, joint * 1  4/97 (4.12%)  5/90 (5.56%)  3/49 (6.12%)  3/61 (4.92%) 
pain, muscle * 1  9/97 (9.28%)  6/90 (6.67%)  0/49 (0.00%)  4/61 (6.56%) 
pain, bone * 1  9/97 (9.28%)  8/90 (8.89%)  4/49 (8.16%)  1/61 (1.64%) 
pain, other * 1  18/97 (18.56%)  10/90 (11.11%)  5/49 (10.20%)  9/61 (14.75%) 
pain, neuralgia / peripheral nerve * 1  5/97 (5.15%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
pain, stomach * 1  5/97 (5.15%)  4/90 (4.44%)  0/49 (0.00%)  0/61 (0.00%) 
pain, chest / thorax NOS * 1  0/97 (0.00%)  0/90 (0.00%)  1/49 (2.04%)  5/61 (8.20%) 
flu-like syndrome * 1  5/97 (5.15%)  20/90 (22.22%)  0/49 (0.00%)  0/61 (0.00%) 
Immune system disorders         
rhinitis * 1  6/97 (6.19%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
Infections and infestations         
infection with normal ANC, urinary tract NOS * 1  7/97 (7.22%)  2/90 (2.22%)  3/49 (6.12%)  0/61 (0.00%) 
infection - other * 1  12/97 (12.37%)  2/90 (2.22%)  5/49 (10.20%)  7/61 (11.48%) 
infection with unknown ANC, urinary tract NOS * 1  5/97 (5.15%)  2/90 (2.22%)  0/49 (0.00%)  0/61 (0.00%) 
infection (documented clinically), urinary tract NOS * 1  0/97 (0.00%)  0/90 (0.00%)  0/49 (0.00%)  4/61 (6.56%) 
infection with normal ANC, upper airway NOS * 1  0/97 (0.00%)  0/90 (0.00%)  3/49 (6.12%)  1/61 (1.64%) 
Metabolism and nutrition disorders         
ALT * 1  5/97 (5.15%)  8/90 (8.89%)  0/49 (0.00%)  0/61 (0.00%) 
AST * 1  6/97 (6.19%)  9/90 (10.00%)  0/49 (0.00%)  0/61 (0.00%) 
creatinine * 1  3/97 (3.09%)  6/90 (6.67%)  3/49 (6.12%)  0/61 (0.00%) 
hyperuricemia * 1  8/97 (8.25%)  2/90 (2.22%)  5/49 (10.20%)  5/61 (8.20%) 
lipase * 1  16/97 (16.49%)  5/90 (5.56%)  1/49 (2.04%)  7/61 (11.48%) 
amylase * 1  0/97 (0.00%)  0/90 (0.00%)  3/49 (6.12%)  3/61 (4.92%) 
hypercalcemia * 1  0/97 (0.00%)  0/90 (0.00%)  0/49 (0.00%)  4/61 (6.56%) 
hypoalbuminemia * 1  0/97 (0.00%)  0/90 (0.00%)  4/49 (8.16%)  2/61 (3.28%) 
hypokalemia * 1  0/97 (0.00%)  0/90 (0.00%)  4/49 (8.16%)  4/61 (6.56%) 
hyponatremia * 1  0/97 (0.00%)  0/90 (0.00%)  3/49 (6.12%)  1/61 (1.64%) 
metabolic / lab - other * 1  0/97 (0.00%)  0/90 (0.00%)  3/49 (6.12%)  4/61 (6.56%) 
Nervous system disorders         
confusion * 1  5/97 (5.15%)  4/90 (4.44%)  0/49 (0.00%)  0/61 (0.00%) 
dizziness * 1  5/97 (5.15%)  9/90 (10.00%)  0/49 (0.00%)  0/61 (0.00%) 
mood alteration, depression * 1  5/97 (5.15%)  15/90 (16.67%)  4/49 (8.16%)  3/61 (4.92%) 
neuropathy: sensory * 1  6/97 (6.19%)  1/90 (1.11%)  3/49 (6.12%)  4/61 (6.56%) 
Renal and urinary disorders         
renal - other * 1  6/97 (6.19%)  0/90 (0.00%)  0/49 (0.00%)  0/61 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
cough * 1  12/97 (12.37%)  15/90 (16.67%)  3/49 (6.12%)  6/61 (9.84%) 
dyspnea (shortness of breath) * 1  13/97 (13.40%)  10/90 (11.11%)  4/49 (8.16%)  4/61 (6.56%) 
voice changes * 1  8/97 (8.25%)  0/90 (0.00%)  0/49 (0.00%)  0/61 (0.00%) 
Skin and subcutaneous tissue disorders         
alopecia * 1  40/97 (41.24%)  6/90 (6.67%)  2/49 (4.08%)  17/61 (27.87%) 
dry skin * 1  10/97 (10.31%)  9/90 (10.00%)  2/49 (4.08%)  6/61 (9.84%) 
hand-foot skin reaction * 1  57/97 (58.76%)  4/90 (4.44%)  8/49 (16.33%)  28/61 (45.90%) 
dermatology - other * 1  7/97 (7.22%)  2/90 (2.22%)  4/49 (8.16%)  5/61 (8.20%) 
pruritus * 1  14/97 (14.43%)  12/90 (13.33%)  1/49 (2.04%)  6/61 (9.84%) 
rash / desquamation * 1  40/97 (41.24%)  8/90 (8.89%)  4/49 (8.16%)  17/61 (27.87%) 
Vascular disorders         
hemorrhage pulmonary, nose * 1  5/97 (5.15%)  1/90 (1.11%)  0/49 (0.00%)  0/61 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, NCI-CTCAE v. 3.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Publication will be discussed with the sponsor prior to release and written consent of the sponsor will be obtained. A draft manuscript of the publication or abstract must be sent to sponsor thirty days in advance of submission.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Therapeutic Area Head
Organization: BAYER
EMail: clinical-trials-contact@bayerhealthcare.com
Layout table for additonal information
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00117637    
Other Study ID Numbers: 11848
2005-000544-86 ( EudraCT Number )
First Submitted: June 30, 2005
First Posted: July 8, 2005
Results First Submitted: August 27, 2010
Results First Posted: December 15, 2010
Last Update Posted: October 31, 2014