Trial Outcomes & Findings for A Randomized, Double-Blinded, Placebo-Controlled Study of Sorafenib in Patients With Advanced Hepatocellular Carcinoma (NCT NCT00492752)

Last Updated: 2014-04-16

Results Overview

Overall Survival (OS) was defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

226 participants

Primary outcome timeframe

From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization

Results posted on

2014-04-16

Participant Flow

Subjects with advanced hepatocellular carcinoma were enrolled from 12 Oct 2005 to 26 Jan 2007 at 23 centers in China (15 centers), Taiwan (5 centers), and Korea (3 centers).

271 subjects were enrolled in a 28-day screening period; 226 subjects were randomized either to Sorafenib or placebo (2:1 ratio) (intent-to-treat \[ITT\] population: for efficacy analysis); 224 subjects received at least one dose of study drug (safety population: for safety analysis). Majority of screen failures did not meet the inclusion criteria.

Participant milestones

Participant milestones
Measure	A1) Sorafenib (Nexavar, BAY43-9006) - no Open Label Phase Participants randomized to Sorafenib treatment until unblinding (August 19, 2007), Sorafenib administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment. Note: Safety Data of participants in the arm presented here are part of the data reported in Reporting Group (RG) 1.	A2) Sorafenib (Nexavar, BAY43-9006) - With Open Label Phase Participants randomized to Sorafenib treatment from until unblinding (August 19, 2007) until end of trial (July 27, 2009), Sorafenib administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment. Note: Safety Data of participants in the arm presented here are part of the data reported in Reporting Group (RG) 1.	B1) Placebo - no Open Label Phase Participants randomized to Sorafenib-matching Placebo until unblinding (August 19, 2007), Placebo tablets matching in appearance were orally administered twice daily (bid). Note: Safety Data of participants in the arm presented here are part of the data reported in Reporting Group (RG) 2.	B2) Placebo First - Then Open Label Sorafenib Treatment Phase Participants switched to Open-label Sorafenib treatment from Placebo after unblinding (August 19, 2007), Sorafenib administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment. Note: Safety Data of participants in the arm presented here are the data reported in Reporting Group (RG) 3.
Double Blind Treatment STARTED	134	16	70	6
Double Blind Treatment Received Treatment	133	16	69	6
Double Blind Treatment COMPLETED	120	16	67	6
Double Blind Treatment NOT COMPLETED	14	0	3	0
Follow-up and/or Open Label Sorafenib STARTED	120	16	67	6
Follow-up and/or Open Label Sorafenib Follow-up Only (no Open Label Treatment)	120	0	67	0
Follow-up and/or Open Label Sorafenib Follow-up First, Then Open Label	0	16	0	6
Follow-up and/or Open Label Sorafenib COMPLETED	34	0	20	0
Follow-up and/or Open Label Sorafenib NOT COMPLETED	86	16	47	6

Reasons for withdrawal

Reasons for withdrawal
Measure	A1) Sorafenib (Nexavar, BAY43-9006) - no Open Label Phase Participants randomized to Sorafenib treatment until unblinding (August 19, 2007), Sorafenib administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment. Note: Safety Data of participants in the arm presented here are part of the data reported in Reporting Group (RG) 1.	A2) Sorafenib (Nexavar, BAY43-9006) - With Open Label Phase Participants randomized to Sorafenib treatment from until unblinding (August 19, 2007) until end of trial (July 27, 2009), Sorafenib administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment. Note: Safety Data of participants in the arm presented here are part of the data reported in Reporting Group (RG) 1.	B1) Placebo - no Open Label Phase Participants randomized to Sorafenib-matching Placebo until unblinding (August 19, 2007), Placebo tablets matching in appearance were orally administered twice daily (bid). Note: Safety Data of participants in the arm presented here are part of the data reported in Reporting Group (RG) 2.	B2) Placebo First - Then Open Label Sorafenib Treatment Phase Participants switched to Open-label Sorafenib treatment from Placebo after unblinding (August 19, 2007), Sorafenib administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment. Note: Safety Data of participants in the arm presented here are the data reported in Reporting Group (RG) 3.
Double Blind Treatment Death	13	0	2	0
Double Blind Treatment Adverse Event	1	0	0	0
Double Blind Treatment Protocol Violation	0	0	1	0
Follow-up and/or Open Label Sorafenib Adverse Event	0	2	0	2
Follow-up and/or Open Label Sorafenib Death	75	5	45	1
Follow-up and/or Open Label Sorafenib Lost to Follow-up	8	1	2	0
Follow-up and/or Open Label Sorafenib Withdrawal by Subject	2	1	0	0
Follow-up and/or Open Label Sorafenib Progression by clinical judgement	0	1	0	2
Follow-up and/or Open Label Sorafenib Radiological and clinical progression	0	0	0	1
Follow-up and/or Open Label Sorafenib Switch to commercial drug	0	6	0	0
Follow-up and/or Open Label Sorafenib Progression measurement proven	1	0	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sorafenib (Nexavar, BAY43-9006) n=150 Participants Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.	Placebo n=76 Participants Placebo tablets matching in appearance were orally administered bid (twice daily).	Total n=226 Participants Total of all reporting groups
Age, Continuous	51 Years n=93 Participants	52 Years n=4 Participants	51 Years n=27 Participants
Age, Customized <65 years	131 Participants n=93 Participants	63 Participants n=4 Participants	194 Participants n=27 Participants
Age, Customized >=65 years	19 Participants n=93 Participants	13 Participants n=4 Participants	32 Participants n=27 Participants
Sex: Female, Male Female	127 Participants n=93 Participants	66 Participants n=4 Participants	193 Participants n=27 Participants
Sex: Female, Male Male	23 Participants n=93 Participants	10 Participants n=4 Participants	33 Participants n=27 Participants
Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0	33 Participants n=93 Participants	22 Participants n=4 Participants	55 Participants n=27 Participants
Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 1	108 Participants n=93 Participants	50 Participants n=4 Participants	158 Participants n=27 Participants
Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 2	9 Participants n=93 Participants	4 Participants n=4 Participants	13 Participants n=27 Participants
Tumor burden Absent	32 Participants n=93 Participants	15 Participants n=4 Participants	47 Participants n=27 Participants
Tumor burden Present	118 Participants n=93 Participants	61 Participants n=4 Participants	179 Participants n=27 Participants

PRIMARY outcome

Timeframe: From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization

Population: In this study the overall survival was measured for the ITT population from the date of randomization until the date of death due to any cause. For patients alive or lost to follow-up at the time of analysis, time to death was to be censored at their last date of follow-up, or at the data cut-off of 09 Aug 2007 (23 months after randomization).

Overall Survival (OS) was defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=150 Participants Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.	Placebo n=76 Participants Placebo tablets matching in appearance were orally administered bid (twice daily).
Overall Survival	198 days Interval 169.0 to 230.0	127 days Interval 114.0 to 166.0

SECONDARY outcome

Timeframe: From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization

Population: Time to Symptomatic Progression was measured for the ITT population (all randomized subjects) up to the data cut-off date of of 09 Aug 2007 (23 months after randomization)

Time to Symptomatic Progression (TTSP) was defined as the time from date of randomization to symptomatic progression. Subjects without symptomatic progression at the time of analysis were censored at their last date of tumor evaluation.

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=150 Participants Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.	Placebo n=76 Participants Placebo tablets matching in appearance were orally administered bid (twice daily).
Time to Symptomatic Progression (TTSP)	105 days Interval 85.0 to 129.0	103 days Interval 73.0 to 124.0

SECONDARY outcome

Timeframe: From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization

Population: Time to progression was measured for the ITT population (all randomized subjects) up to the data cut-off date of 09 Aug 2007 (23 months after randomization).

Time to progression (TTP) was defined as the time from date of randomization to radiologically documented disease progression. Subjects without progression at the time of analysis were censored at their last date of tumor evaluation。

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=150 Participants Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.	Placebo n=76 Participants Placebo tablets matching in appearance were orally administered bid (twice daily).
Time to Progression (TTP)	84 days Interval 80.0 to 109.0	41.5 days Interval 41.0 to 47.0

SECONDARY outcome

Timeframe: From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization

Population: Disease control rate was measured for the ITT population (all randomized subjects)

Disease Control (DC) was defined as the total number of subjects whose best response was not Progressive Disease (PD: an increase in the sum of tumor lesions sizes) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR: disappearance of tumor lesions) + total number of Partial Response (PR: a decrease of at least 30% in the sum of tumor lesion sizes) + total number of Stable Disease (SD: steady state of disease); CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating).

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=150 Participants Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.	Placebo n=76 Participants Placebo tablets matching in appearance were orally administered bid (twice daily).
Disease Control Yes	53 participants	12 participants
Disease Control No	97 participants	64 participants

SECONDARY outcome

Timeframe: Baseline up to Cycle 1 and Cycle 3. From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization

Population: FHSI-8 score changes from baseline by visit were assessed for the ITT population.

The FHSI-8 questionnaire was completed at baseline and every 3 weeks during treatment and at the end of treatment visit only for subjects who withdrew for reasons other than symptomatic progression. Patient reported outcome was measured using the FHSI-8 score changes from baseline throughout the study period. FHSI-8 assesses hepatobiliary cancer symptoms with total score ranges from 0 to 32 (0 = the best quality of life; 32 = the worst quality of life with severe symptoms)..

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=150 Participants Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.	Placebo n=76 Participants Placebo tablets matching in appearance were orally administered bid (twice daily).
Change in Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8) Score From Baseline to Cycle 1 and Cycle 3 cycle 1	26 scores on a scale Standard Deviation 4.8	26 scores on a scale Standard Deviation 4.8
Change in Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8) Score From Baseline to Cycle 1 and Cycle 3 cycle 3	24 scores on a scale Standard Deviation 6.3	25 scores on a scale Standard Deviation 5.3

SECONDARY outcome

Timeframe: Baseline up to Cycle 3 and end of treatment. From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization

Population: FACT-Hep score changes from baseline by visit were assessed for the ITT population.

The FACT-Hep questionnaire was also completed to assess patient reported outcome. The FACT-Hep assesses hepatobiliary cancer-related quality of life. FACT-Hep total score ranges from 0 to 180 (0=All questions answered "Not at all"; 180=All questions answered "Very much").

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=150 Participants Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.	Placebo n=76 Participants Placebo tablets matching in appearance were orally administered bid (twice daily).
Change in Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) Score From Baseline to Cycle 3 and End of Treatment cycle 3	-10 scores on a scale Standard Deviation 25.5	-3 scores on a scale Standard Deviation 19.9
Change in Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) Score From Baseline to Cycle 3 and End of Treatment end of treatment	-25 scores on a scale Standard Deviation 27.2	-23 scores on a scale Standard Deviation 31.3

SECONDARY outcome

Timeframe: From randomization/start of treatment of the first subject until approximately 23 months after randomization when the subjects on placebo were offered the option to crossover to sorafenib treatment

Population: The tumor response was measured for the ITT population.

Tumor Response (= Best Overall Response) of a subject was defined as the best tumor response (confirmed Complete Response (CR: disappearance of tumor lesions), confirmed\* Partial Response (PR: a decrease of at least 30% in the sum of tumor lesion sizes), Stable Disease (SD: steady state of disease), or Progressive Disease (PD: an increase in the sum of tumor lesions sizes)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=150 Participants Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.	Placebo n=76 Participants Placebo tablets matching in appearance were orally administered bid (twice daily).
Number of Participants With Different Tumor Response Complete Response (CR)	0 participants	0 participants
Number of Participants With Different Tumor Response Partial Response (PR)	5 participants	1 participants
Number of Participants With Different Tumor Response Stable Disease (SD)	81 participants	21 participants
Number of Participants With Different Tumor Response Progressive Disease (PD)	46 participants	41 participants
Number of Participants With Different Tumor Response Not assessable	18 participants	13 participants

SECONDARY outcome

Timeframe: From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization

Population: The duration of response was measured for the ITT population.

Duration of Response was defined as the time from date of first response (Complete Response (CR) or Partial Response (PR)) to the date when Progressive Disease (PD) is first documented, or to the date of death, whichever occurs first. Subjects still having CR or PR at the time of analysis were censored at their last tumor assessment.

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=5 Participants Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.	Placebo n=1 Participants Placebo tablets matching in appearance were orally administered bid (twice daily).
Duration of Response	210 days Interval 82.0 to 343.0	252 days Interval 252.0 to 252.0

SECONDARY outcome

Timeframe: From randomization of the first subject until the data cut-off date approximately 23 months after start of randomization

Population: The time to response was measured for the ITT population.

Time to Response (TTR) for subjects who achieved a response (Complete Response (CR) or Partial Response (PR) ) was defined as the time from date of randomization to the earliest date that the response was first documented.

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=5 Participants Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.	Placebo n=1 Participants Placebo tablets matching in appearance were orally administered bid (twice daily).
Time to Response	84 days Interval 45.0 to 126.0	42 days Interval 42.0 to 42.0

SECONDARY outcome

Timeframe: PK assessments made at following times: pre-dose, 1 h, 2h, 4h, 8h,and 12h after at least 21 consecutive doses during Cycle 1

Population: The stated goal in the protocol was to obtain PK data from approximately 39 patients. As this was only descriptive information, the sample size was not critical. All patients who provided PK data were included in the analysis.

The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. A plot of concentration vs time after dosing is created, and the area under this curve is calculated by standard methods (eg, trapezoidal rule) to provide a measure of how much drug was in the bloodstream following dosing.

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=24 Participants Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.	Placebo Placebo tablets matching in appearance were orally administered bid (twice daily).
Area Under the Curve From Time 0 to 12 Hours Post-dose (AUC 0-12) After 21 Days of Sorafenib Treatment	35.7 mg*h/L Interval 7.8 to 149.2	—

SECONDARY outcome

Timeframe: PK assessments made at following times: pre-dose, 1 h, 2h, 4h, 8h,and 12h after at least 21 consecutive doses during Cycle 1

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=24 Participants Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.	Placebo Placebo tablets matching in appearance were orally administered bid (twice daily).
Normalized Area Under the Curve (AUC Norm) After 21 Days of Sorafenib Treatment	6.6 g*h/L Interval 1.3 to 21.6	—

SECONDARY outcome

Timeframe: PK assessments made at following times: pre-dose, 1 h, 2h, 4h, 8h,and 12h after at least 21 consecutive doses during Cycle 1

Cmax refers to the highest plasma concentration of drug reached after dosing. It is obtained by collecting a series of blood samples after dosing, and analyzing them for drug content by a sensitive and specific analytical method. The highest measured concentration is referred to as the Cmax.

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=24 Participants Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.	Placebo Placebo tablets matching in appearance were orally administered bid (twice daily).
Maximum Concentration (Cmax) After 21 Days of Sorafenib Treatment	4.44 mg/L Interval 1.121 to 16.7	—

SECONDARY outcome

Timeframe: PK assessments made at following times: pre-dose, 1 h, 2h, 4h, 8h,and 12h after at least 21 consecutive doses during Cycle 1

Cmaxnorm refers to the maximum plasma concentration of Sorafenib corrected for dose and body weight (Cmaxnorm = Cmax/(mg/kg)).

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=24 Participants Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.	Placebo Placebo tablets matching in appearance were orally administered bid (twice daily).
Normalized Maximum Concentration (Cmaxnorm) After 21 Days of Sorafenib Treatment	0.66 g/mL Interval 0.18 to 2.43	—

SECONDARY outcome

Timeframe: PK assessments made at following times: pre-dose, 1 h, 2h, 4h, 8h,and 12h after at least 21 consecutive doses during Cycle 1

Tmax refers to the time after dosing when a drug attains its maximum concentration in the blood. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content. The time corresponding to the highest measurable concentration (Cmax) is referred to as Tmax.

Outcome measures

Outcome measures
Measure	Sorafenib (Nexavar, BAY43-9006) n=24 Participants Sorafenib was administered orally at a dose of 400 mg (2 x 200 mg tablets) bid (twice daily); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily (od) and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.	Placebo Placebo tablets matching in appearance were orally administered bid (twice daily).
Time of Maximum Concentration (Tmax) After 21 Days of Sorafenib Treatment	4.0 hours Interval 0.5 to 12.0	—

Adverse Events

Sorafenib, All (Double-Blind and Open Label Phase)

Serious events: 76 serious events

Other events: 144 other events

Deaths: 0 deaths

Placebo, All (Double-Blind and Open Label Phase)

Serious events: 34 serious events

Other events: 65 other events

Deaths: 0 deaths

Placebo, Open Label Only (Participants Switched to Sorafenib)

Serious events: 3 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Therapeutic Area Head

BAYER

Phone: <not disclosed>

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Investigator must send a draft manuscript to be submitted for publication or to be presented or abstract to Bayer at least 60 days in advance of submission in order to obtain approval prior to submission of the final version for publication or presentation. In case of a difference of opinion between Bayer and the Investigator(s), the contents of the publication will be discussed in order to find a solution, which satisfies both parties.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Sorafenib, All (Double-Blind and Open Label Phase) n=149 participants at risk Reporting Group 1 (RG 1): All participants randomized to Sorafenib treatment (data from start of treatment until end of trial \[July 27, 2009\]). Sorafenib administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.	Placebo, All (Double-Blind and Open Label Phase) n=75 participants at risk Reporting Group 2 (RG 2): All participants randomized to Sorafenib-matching Placebo (data from start of treatment until end of trial \[July 27, 2009\]). Treatment for Double-Blind phase (before unblinding \[August 19, 2007\]): Placebo tablets matching in appearance were orally administered twice daily (bid); Treatment for Open Label phase (after unblinding \[August 19, 2007\]): Sorafenib administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.	Placebo, Open Label Only (Participants Switched to Sorafenib) n=6 participants at risk Reporting Group 3 (RG 3): Participants switched to Open-label Sorafenib treatment from Placebo ( Data after unblinding \[August 19, 2007\] until end of this trial \[July 27, 2009\]). Sorafenib administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.
Cardiac disorders Hypertension	0.67% 1/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Cardiac disorders Cardiac General - Other	0.00% 0/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	1.3% 1/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
General disorders Death Not Associated With CTCAE Term, Disease Progression NOS	14.8% 22/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	10.7% 8/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	16.7% 1/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
General disorders Death Not Associated With CTCAE Term, Multi - Organ Failure	2.0% 3/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	4.0% 3/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	16.7% 1/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
General disorders Death Not Associated With CTCAE Term, Sudden Death	2.0% 3/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	1.3% 1/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
General disorders Fever	3.4% 5/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	4.0% 3/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
General disorders Fatigue	1.3% 2/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	1.3% 1/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
General disorders Constitutional Symptoms - Other	0.67% 1/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
General disorders Rigors / Chills	0.67% 1/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Gastrointestinal disorders Anorexia	1.3% 2/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Gastrointestinal disorders Ascites	4.7% 7/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	4.0% 3/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Gastrointestinal disorders Colitis	0.67% 1/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Gastrointestinal disorders Diarrhea	2.7% 4/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Gastrointestinal disorders Distension	1.3% 2/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	2.7% 2/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Gastrointestinal disorders Dysphagia	0.67% 1/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Gastrointestinal disorders Mucositis (Functional/Symptomatic), Oral Cavity	0.67% 1/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Gastrointestinal disorders Nausea	0.67% 1/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Gastrointestinal disorders Ileus	0.00% 0/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	1.3% 1/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Gastrointestinal disorders GI - Other	1.3% 2/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	1.3% 1/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Gastrointestinal disorders Stricture, GI, Biliary Tree	1.3% 2/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Gastrointestinal disorders Vomiting	0.67% 1/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Vascular disorders CNS Hemorrhage	0.67% 1/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Vascular disorders Hemorrhage, GI, Abdomen NOS	0.67% 1/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Vascular disorders Hemorrhage, GI, Anus	0.00% 0/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	1.3% 1/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Vascular disorders Hemorrhage, GI, Varices (Esophageal)	2.7% 4/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	1.3% 1/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Vascular disorders Hemorrhage, GI, Stomach	0.67% 1/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Vascular disorders Hemorrhage, GI, Liver	0.00% 0/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	1.3% 1/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Vascular disorders Hemorrhage, GI, Upper GI NOS	6.0% 9/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	5.3% 4/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Vascular disorders Hemorrhage - Other	0.67% 1/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Vascular disorders Hemorrhage Pulmonary, Nose	0.67% 1/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Vascular disorders Hemorrhage Pulmonary, Respiratory Tract NOS	0.00% 0/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	1.3% 1/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Hepatobiliary disorders Liver Dysfunction	4.0% 6/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	10.7% 8/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Hepatobiliary disorders Hepatobiliary - Other	0.67% 1/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	1.3% 1/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Infections and infestations Febrile Neutropenia	0.67% 1/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Infections and infestations Infection - Other	1.3% 2/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	1.3% 1/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Infections and infestations Infection With Unknown ANC, Biliary Tree	0.00% 0/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	1.3% 1/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Infections and infestations Infection With Unknown ANC, Lung (Pneumonia)	2.7% 4/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	1.3% 1/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Infections and infestations Infection With Unknown ANC, Wound	0.67% 1/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Blood and lymphatic system disorders Edema: Limb	1.3% 2/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Musculoskeletal and connective tissue disorders Fracture	0.67% 1/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).

Other adverse events
Measure	Sorafenib, All (Double-Blind and Open Label Phase) n=149 participants at risk Reporting Group 1 (RG 1): All participants randomized to Sorafenib treatment (data from start of treatment until end of trial \[July 27, 2009\]). Sorafenib administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.	Placebo, All (Double-Blind and Open Label Phase) n=75 participants at risk Reporting Group 2 (RG 2): All participants randomized to Sorafenib-matching Placebo (data from start of treatment until end of trial \[July 27, 2009\]). Treatment for Double-Blind phase (before unblinding \[August 19, 2007\]): Placebo tablets matching in appearance were orally administered twice daily (bid); Treatment for Open Label phase (after unblinding \[August 19, 2007\]): Sorafenib administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.	Placebo, Open Label Only (Participants Switched to Sorafenib) n=6 participants at risk Reporting Group 3 (RG 3): Participants switched to Open-label Sorafenib treatment from Placebo ( Data after unblinding \[August 19, 2007\] until end of this trial \[July 27, 2009\]). Sorafenib administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid); 2 dose reductions to predefined levels of 400 mg (2 x 200 mg tablets) once daily and 400 mg (2 x 200 mg tablets) every 2 days were permitted for treatment-emergent adverse events related to study treatment.
Immune system disorders Allergic Reaction	1.3% 2/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	5.3% 4/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Ear and labyrinth disorders Tinnitus	8.1% 12/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Blood and lymphatic system disorders Blood - Other	5.4% 8/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	1.3% 1/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Blood and lymphatic system disorders Hemoglobin	19.5% 29/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	13.3% 10/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Blood and lymphatic system disorders Leukocytes	12.1% 18/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	5.3% 4/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Blood and lymphatic system disorders Platelets	23.5% 35/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	13.3% 10/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	16.7% 1/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Cardiac disorders Hypertension	22.1% 33/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	5.3% 4/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Blood and lymphatic system disorders PTT	8.1% 12/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	5.3% 4/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
General disorders Fatigue	34.2% 51/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	20.0% 15/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
General disorders Fever	25.5% 38/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	10.7% 8/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
General disorders Insomnia	16.8% 25/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	22.7% 17/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
General disorders Weight Loss	41.6% 62/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	17.3% 13/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Skin and subcutaneous tissue disorders Alopecia	26.8% 40/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	1.3% 1/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Skin and subcutaneous tissue disorders Dermatology - Other	10.1% 15/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	4.0% 3/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Skin and subcutaneous tissue disorders Hand - Foot Skin Reaction	46.3% 69/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	2.7% 2/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	33.3% 2/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Skin and subcutaneous tissue disorders Pruritus	12.8% 19/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	12.0% 9/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Skin and subcutaneous tissue disorders Rash / Desquamation	22.1% 33/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	9.3% 7/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Endocrine disorders Hypothyroidism	0.00% 0/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	16.7% 1/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Gastrointestinal disorders Anorexia	30.9% 46/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	17.3% 13/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Gastrointestinal disorders Ascites	27.5% 41/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	17.3% 13/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Gastrointestinal disorders Constipation	13.4% 20/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	16.0% 12/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Gastrointestinal disorders Diarrhea	43.0% 64/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	16.0% 12/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	50.0% 3/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Gastrointestinal disorders Distension	16.1% 24/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	20.0% 15/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Gastrointestinal disorders GI - Other	6.7% 10/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	1.3% 1/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Gastrointestinal disorders Mucositis (Clinical Exam), Oral Cavity	4.0% 6/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	2.7% 2/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	16.7% 1/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Gastrointestinal disorders Nausea	24.8% 37/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	25.3% 19/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Gastrointestinal disorders Vomiting	16.8% 25/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	17.3% 13/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Vascular disorders Hemorrhage Pulmonary, Respiratory Tract NOS	1.3% 2/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	1.3% 1/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	16.7% 1/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Hepatobiliary disorders Hepatobiliary - Other	5.4% 8/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	8.0% 6/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Infections and infestations Infection - Other	6.7% 10/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	8.0% 6/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Blood and lymphatic system disorders Edema: Limb	6.7% 10/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	10.7% 8/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Metabolism and nutrition disorders Alkaline Phosphatase	26.2% 39/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	18.7% 14/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Metabolism and nutrition disorders ALT	32.9% 49/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	24.0% 18/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	33.3% 2/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Metabolism and nutrition disorders Amylase	5.4% 8/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Metabolism and nutrition disorders AST	42.3% 63/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	30.7% 23/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	16.7% 1/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Metabolism and nutrition disorders Bilirubin (Hyperbilirubinemia)	37.6% 56/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	32.0% 24/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	33.3% 2/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Metabolism and nutrition disorders Creatinine	6.7% 10/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	4.0% 3/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Metabolism and nutrition disorders GGT	6.0% 9/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	9.3% 7/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Metabolism and nutrition disorders Hyperglycemia	5.4% 8/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	9.3% 7/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).
Metabolism and nutrition disorders Hyperkalemia	4.7% 7/149 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	6.7% 5/75 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).	0.00% 0/6 • Reporting Group (RG) 1 + 2: Data from start of treatment until end of this trial (July 27, 2009); RG 3: Data after unblinding (August 19, 2007) until end of this trial (July 27, 2009). Acronyms in Adverse Event section: Gastrointestinal (GI), Common Terminology Criteria for Adverse Events (CTCAE), not otherwise specified (NOS), absolute neutrophil count (ANC), Central nervous system (CNS), Partial thromboplastin time (PTT), Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma glutamyl transpeptidase (GGT).