A Phase II Randomized, Double-blind, Placebo-controlled Study of Sorafenib or Placebo in Combination With Transarterial Chemoembolization (TACE) Performed With DC Bead and Doxorubicin for Intermediate Stage Hepatocellular Carcinoma (HCC).

• ClinicalTrials.gov Identifier: NCT00855218
• Recruitment Status: Completed
• First Posted: March 4, 2009
• Results First Posted: September 24, 2012
• Last Update Posted: August 18, 2017
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Carcinoma, Hepatocellular
• Interventions: Drug: Sorafenib (Nexavar, BAY43-9006); Drug: Placebo
• Enrollment: 307

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Sorafenib (Nexavar, BAY43-9006) + TACE	Placebo + TACE
Arm/Group Description	Sorafenib was to be orally administered as 2 x 200 mg tablets bid (twice daily). Participants were then also treated with Transarterial Chemoembolization (TACE) performed with doxorubicin capable beads (DC Bead) (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of sorafenib, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)	Placebo was to be orally administered as 2 tablets bid (twice daily). Participants were then also treated with TACE performed with doxorubicin capable beads (DC Bead) (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of placebo, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)
Period Title: Overall Study
Started	154	153
Participants Received Treatment	153	151
Completed	0	0
Not Completed	154	153
Reason Not Completed
Adverse Event	43	27
Withdrawal by Subject	10	6
Physician Decision	18	11
Lost to Follow-up	0	1
Protocol Violation	5	9
non-compliant with study drug	3	1
patient convenience	2	0
technical problems	2	1
Still treated with study medication	0	1
Untreatable disease progression	54	67
Second malignancy	0	1
Progression measurement proven	7	15
Clinical endpoint reached	10	13

Baseline Characteristics

Arm/Group Title		Sorafenib (Nexavar, BAY43-9006) + TACE	Placebo + TACE	Total
Arm/Group Description		Sorafenib was to be orally administered as 2 x 200 mg tablets bid (twice daily). Participants were then also treated with Transarterial Chemoembolization (TACE) performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of sorafenib, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)	Placebo was to be orally administered as 2 tablets bid (twice daily). Participants were then also treated with TACE performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of placebo, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)	Total of all reporting groups
Overall Number of Baseline Participants		154	153	307
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	154 participants	153 participants	307 participants
		62.5 (11.9)	62.7 (11.9)	62.6 (11.9)
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	154 participants	153 participants	307 participants
<65 years		77	82	159
65 - 74 years		52	48	100
>=75 years		25	23	48
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	154 participants	153 participants	307 participants
	Female	19 12.3%	27 17.6%	46 15.0%
	Male	135 87.7%	126 82.4%	261 85.0%
Eastern Cooperative Oncology Group (ECOG) performance status at enrollment [1]; Measure Type: Number; Unit of measure: Scores on a scale	Number Analyzed	154 participants	153 participants	307 participants
Missing		0	1	1
Grade 0		154	152	306
		[1] Measure Description: Measures on a scale from grade 0 (best) to grade 5 (worst) cancer's affect on patient's life. 0=Fully active without restriction; 1= Restricted in physically strenuous activity; 2= Ambulatory, capable of all selfcare; 3= Capable of limited selfcare; 4= Completely disabled; 5= Dead
Number of target lesions; Measure Type: Number; Unit of measure: Participants	Number Analyzed	154 participants	153 participants	307 participants
1		30	31	61
2		58	49	107
3		33	33	66
4		12	18	30
5		21	22	43
Number of non-target lesions; Measure Type: Number; Unit of measure: Participants	Number Analyzed	154 participants	153 participants	307 participants
0		72	73	145
1		40	39	79
2		24	18	42
3		7	10	17
4		3	6	9
5		4	2	6
6		0	1	1
7		1	2	3
8		1	1	2
10		1	1	2
14		1	0	1
Alfa-fetoprotein; Measure Type: Number; Unit of measure: Participants	Number Analyzed	154 participants	153 participants	307 participants
<400 ng/mL		113	112	225
>/=400 ng/mL		41	41	82
Child pugh classification [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	154 participants	153 participants	307 participants
Missing		0	1	1
Class A		153	152	305
Class B		1	0	1
		[1] Measure Description: Used to assess the severity of a participant's liver disease, the prognosis, and the appropriate treatment. A Child-Pugh class A (well-compensated disease); class B (significant functional compromise); and class C (decompensated disease).
Time of first study medication since initial diagnosis [1]; Median (Full Range); Unit of measure: Months
	Number Analyzed	154 participants	153 participants	307 participants
		1.60; (0.1 to 47.6)	1.91; (0.1 to 96.4)	1.71; (0.1 to 96.4)
		[1] Measure Description: This variable shows time from the first diagnosis of HCC until the first treatment with study drug.
Time of first study medication since first progression [1]; Median (Full Range); Unit of measure: Months
	Number Analyzed	154 participants	153 participants	307 participants
		1.45; (0.2 to 22.0)	2.56; (0.2 to 28.9)	1.91; (0.2 to 28.9)
		[1] Measure Description: This variable shows the time from the first treatment with study drug until radiological confirmed disease progression.
Time of first study medication since most recent progression; Median (Full Range); Unit of measure: Months
	Number Analyzed	154 participants	153 participants	307 participants
		1.02; (0.2 to 6.8)	1.25; (0.2 to 8.1)	1.09; (0.2 to 8.1)

Outcome Measures

1. Primary Outcome

Title	Time to Progression (TTP) - Independent Radiological Review (Primary Analysis)
Description	TTP is defined as the time (days) from randomization to radiological confirmed disease progression. Participants without progression at the time of analysis were censored at their last date of tumor evaluation.
Time Frame	From randomization of the first participant until 28 months later (cut-off date)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT)

Arm/Group Title	Sorafenib (Nexavar, BAY43-9006) + TACE	Placebo + TACE
Arm/Group Description:	Sorafenib was to be orally administered as 2 x 200 mg tablets bid (twice daily). Participants were then also treated with Transarterial Chemoembolization (TACE) performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of sorafenib, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)	Placebo was to be orally administered as 2 tablets bid (twice daily). Participants were then also treated with TACE performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of placebo, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)
Overall Number of Participants Analyzed	154	153
Median (95% Confidence Interval); Unit of Measure: Days
	169; (166 to 219)	166; (113 to 168)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sorafenib (Nexavar, BAY43-9006) + TACE, Placebo + TACE
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.072
	Comments	stratified one-sided (alpha=0.15). adjusted for region and Alfa-fetoprotein (AFP) level at baseline.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.797
	Confidence Interval	95%; 0.588 to 1.080
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall Survival (OS) was defined as the time (days) from randomization to death due to any cause. Participants still alive at the time of analysis were censored at their last date of last contact.
Time Frame	From randomization of the first participant until 28 months later (cut-off date)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT)

Arm/Group Title	Sorafenib (Nexavar, BAY43-9006) + TACE	Placebo + TACE
Arm/Group Description:	Sorafenib was to be orally administered as 2 x 200 mg tablets bid (twice daily). Participants were then also treated with Transarterial Chemoembolization (TACE) performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of sorafenib, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)	Placebo was to be orally administered as 2 tablets bid (twice daily). Participants were then also treated with TACE performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of placebo, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)
Overall Number of Participants Analyzed	154	153
Median (95% Confidence Interval); Unit of Measure: Days
	NA [1]; (554 to NA)	NA [1]; (562 to NA)

[1]

Value cannot be estimated due to censored data

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sorafenib (Nexavar, BAY43-9006) + TACE, Placebo + TACE
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.295
	Comments	[Not Specified]
	Method	Log Rank
	Comments	stratified one-sided (alpha=0.15). adjusted for region and AFP level at baseline.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.898
	Confidence Interval	95%; 0.606 to 1.330
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Time to Untreatable Progression (TTUP)
Description	Time to untreatable progression (TTUP) was defined as the time (days) from randomization to untreatable progression. Participants without untreatable progression at the time of analysis were censored at their last date of tumor evaluation.
Time Frame	From randomization of the first participant until 28 months later (cut-off date)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT)

Arm/Group Title	Sorafenib (Nexavar, BAY43-9006) + TACE	Placebo + TACE
Arm/Group Description:	Sorafenib was to be orally administered as 2 x 200 mg tablets bid (twice daily). Participants were then also treated with Transarterial Chemoembolization (TACE) performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of sorafenib, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)	Placebo was to be orally administered as 2 tablets bid (twice daily). Participants were then also treated with TACE performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of placebo, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)
Overall Number of Participants Analyzed	154	153
Median (95% Confidence Interval); Unit of Measure: Days
	95; (62 to 113)	224; (158 to 288)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sorafenib (Nexavar, BAY43-9006) + TACE, Placebo + TACE
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.999
	Comments	[Not Specified]
	Method	Log Rank
	Comments	startified one-sided (alpha=0.15), adjusted for region and AFP level at baseline
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.586
	Confidence Interval	95%; 1.200 to 2.096
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Time to Vascular Invasion/Extrahepatic Spread (TTVI/ES)
Description	Time to vascular invasion/extrahepatic spread (TTVI/ES) was defined as the time (days) from randomization to vascular invasion/extrahepatic spread. Participants without vascular invasion/extrahepatic spread at the time of analysis were censored at their last date of tumor evaluation.
Time Frame	From randomization of the first participant until 28 months later (cut-off date)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT)

Arm/Group Title	Sorafenib (Nexavar, BAY43-9006) + TACE	Placebo + TACE
Arm/Group Description:	Sorafenib was to be orally administered as 2 x 200 mg tablets bid (twice daily). Participants were then also treated with Transarterial Chemoembolization (TACE) performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of sorafenib, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)	Placebo was to be orally administered as 2 tablets bid (twice daily). Participants were then also treated with TACE performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of placebo, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)
Overall Number of Participants Analyzed	154	153
Median (95% Confidence Interval); Unit of Measure: Days
	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

Value cannot be estimated due to censored data

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sorafenib (Nexavar, BAY43-9006) + TACE, Placebo + TACE
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.076
	Comments	[Not Specified]
	Method	Log Rank
	Comments	stratified one sided (alpha=0.15), adjusted on region and AFP level at baseline
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.621
	Confidence Interval	95%; 0.321 to 1.200
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Tumor Response - Independent Radiological Review
Description	Tumor Response was defined as the number of participants with a confirmed Complete Response (CR)=disappearance of all clinical and radiological tumor lesions, Partial Response (PR)= at least 30% decrease in sum of the longest diameters (LD) of tumor lesions, Stable Disease (SD)= neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease, or Progressive Disease (PD)=at least 20% increase in the sum of LD of measured lesions, observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
Time Frame	From randomization of the first participant until 28 months later (cut-off date)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT)

Arm/Group Title	Sorafenib (Nexavar, BAY43-9006) + TACE	Placebo + TACE
Arm/Group Description:	Sorafenib was to be orally administered as 2 x 200 mg tablets bid (twice daily). Participants were then also treated with Transarterial Chemoembolization (TACE) performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of sorafenib, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)	Placebo was to be orally administered as 2 tablets bid (twice daily). Participants were then also treated with TACE performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of placebo, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)
Overall Number of Participants Analyzed	154	153
Measure Type: Number; Unit of Measure: Participants
Response (CR+PR)	55	43
Complete Response (CR)	20	17
Partial Response (PR)	35	26
Stable Disease	52	56
Progressive Disease	20	36
Not assessable	27	18

6. Secondary Outcome

Title	Tumor Response - Investigator Assessment
Description	Tumor Response was defined as the number of participants with a confirmed Complete Response (CR)=disappearance of all clinical and radiological tumor lesions, Partial Response (PR)= at least 30% decrease in sum of the longest diameters (LD) of tumor lesions, Stable Disease (SD)= neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease, or Progressive Disease (PD)=at least 20% increase in the sum of LD of measured lesions, observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
Time Frame	From randomization of the first participant until 28 months later (cut-off date)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT)

Arm/Group Title	Sorafenib (Nexavar, BAY43-9006) + TACE	Placebo + TACE
Arm/Group Description:	Sorafenib was to be orally administered as 2 x 200 mg tablets bid (twice daily). Participants were then also treated with Transarterial Chemoembolization (TACE) performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of sorafenib, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)	Placebo was to be orally administered as 2 tablets bid (twice daily). Participants were then also treated with TACE performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of placebo, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)
Overall Number of Participants Analyzed	154	153
Measure Type: Number; Unit of Measure: Participants
Response (CR+PR)	66	53
Complete Response	21	20
Partial Response	45	33
Stable Disease	50	57
Progressive Disease	16	30
Not Assessable	22	13

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	Acronyms used: Gastrointestinal (GI), Genitourinary (GU), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Aspartate aminotransferase (AST), Acute respiratory distress syndrome (ARDS), Alanine aminotransferase (ALT), Common Terminology Criteria for Adverse Events (CTCAE)
Arm/Group Title	Sorafenib (Nexavar, BAY43-9006) + TACE	Placebo + TACE
Arm/Group Description	Sorafenib was to be orally administered as 2 x 200 mg tablets bid (twice daily). Patients were then also treated with TACE performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of sorafenib on cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)	Placebo was to be orally administered as 2 tablets bid (twice daily). Patients were then also treated with TACE performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of placebo on cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)
All-Cause Mortality
	Sorafenib (Nexavar, BAY43-9006) + TACE	Placebo + TACE
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Sorafenib (Nexavar, BAY43-9006) + TACE	Placebo + TACE
	Affected / at Risk (%)	Affected / at Risk (%)
Total	86/153 (56.21%)	56/151 (37.09%)
Blood and lymphatic system disorders
BLOOD - OTHER * 1	0/153 (0.00%)	1/151 (0.66%)
EDEMA: LIMB * 1	0/153 (0.00%)	1/151 (0.66%)
HEMOGLOBIN * 1	4/153 (2.61%)	1/151 (0.66%)
LYMPHOPENIA * 1	1/153 (0.65%)	0/151 (0.00%)
PLATELETS * 1	1/153 (0.65%)	0/151 (0.00%)
Cardiac disorders
CARDIAC GENERAL - OTHER * 1	0/153 (0.00%)	1/151 (0.66%)
CARDIAC ISCHEMIA/INFARCTION * 1	3/153 (1.96%)	2/151 (1.32%)
CARDIOPULMONARY ARREST * 1	1/153 (0.65%)	0/151 (0.00%)
HYPERTENSION * 1	0/153 (0.00%)	1/151 (0.66%)
LEFT VENTRICULAR SYSTOLIC DYSFUNCTION * 1	1/153 (0.65%)	0/151 (0.00%)
SUPRAVENTRICULAR ARRHYTHMIA, ATRIAL FIBRILLATION * 1	1/153 (0.65%)	0/151 (0.00%)
Endocrine disorders
DIABETES * 1	2/153 (1.31%)	0/151 (0.00%)
Gastrointestinal disorders
ASCITES * 1	6/153 (3.92%)	2/151 (1.32%)
CONSTIPATION * 1	1/153 (0.65%)	1/151 (0.66%)
DEHYDRATION * 1	1/153 (0.65%)	0/151 (0.00%)
DIARRHEA * 1	1/153 (0.65%)	0/151 (0.00%)
GASTRITIS * 1	1/153 (0.65%)	0/151 (0.00%)
GI - OTHER * 1	2/153 (1.31%)	0/151 (0.00%)
HEARTBURN * 1	1/153 (0.65%)	0/151 (0.00%)
ILEUS * 1	0/153 (0.00%)	1/151 (0.66%)
LEAK, GI, BILIARY TREE * 1	1/153 (0.65%)	0/151 (0.00%)
NAUSEA * 1	1/153 (0.65%)	1/151 (0.66%)
PERFORATION, GI, DUODENUM * 1	0/153 (0.00%)	1/151 (0.66%)
PERFORATION, GI, GALLBLADDER * 1	1/153 (0.65%)	0/151 (0.00%)
PERFORATION, GI, STOMACH * 1	1/153 (0.65%)	0/151 (0.00%)
VOMITING * 1	1/153 (0.65%)	2/151 (1.32%)
General disorders
CONSTITUTIONAL SYMPTOMS - OTHER * 1	2/153 (1.31%)	0/151 (0.00%)
DEATH NOT ASSOCIATED WITH CTCAE TERM, DISEASE PROGRESSION NOS * 1	1/153 (0.65%)	2/151 (1.32%)
DEATH NOT ASSOCIATED WITH CTCAE TERM, MULTI-ORGAN FAILURE * 1	0/153 (0.00%)	1/151 (0.66%)
DEATH NOT ASSOCIATED WITH CTCAE TERM, SUDDEN DEATH * 1	0/153 (0.00%)	1/151 (0.66%)
FATIGUE * 1	5/153 (3.27%)	1/151 (0.66%)
FEVER * 1	4/153 (2.61%)	6/151 (3.97%)
PAIN, ABDOMEN NOS * 1	5/153 (3.27%)	7/151 (4.64%)
PAIN, BACK * 1	1/153 (0.65%)	0/151 (0.00%)
PAIN, BONE * 1	1/153 (0.65%)	0/151 (0.00%)
PAIN, CHEST WALL * 1	0/153 (0.00%)	1/151 (0.66%)
PAIN, GALLBLADDER * 1	0/153 (0.00%)	1/151 (0.66%)
PAIN, JOINT * 1	1/153 (0.65%)	1/151 (0.66%)
PAIN, PLEURA * 1	0/153 (0.00%)	1/151 (0.66%)
PAIN, STOMACH * 1	1/153 (0.65%)	0/151 (0.00%)
SYNDROMES - OTHER * 1	2/153 (1.31%)	2/151 (1.32%)
Hepatobiliary disorders
CHOLECYSTITIS * 1	4/153 (2.61%)	2/151 (1.32%)
HEPATOBILIARY - OTHER * 1	6/153 (3.92%)	4/151 (2.65%)
LIVER DYSFUNCTION * 1	11/153 (7.19%)	5/151 (3.31%)
PANCREATITIS * 1	0/153 (0.00%)	2/151 (1.32%)
Infections and infestations
INFECTION (DOCUMENTED CLINICALLY), BLADDER (URINARY) * 1	1/153 (0.65%)	0/151 (0.00%)
INFECTION (DOCUMENTED CLINICALLY), BLOOD * 1	1/153 (0.65%)	2/151 (1.32%)
INFECTION (DOCUMENTED CLINICALLY), BRONCHUS * 1	0/153 (0.00%)	1/151 (0.66%)
INFECTION (DOCUMENTED CLINICALLY), COLON * 1	0/153 (0.00%)	1/151 (0.66%)
INFECTION (DOCUMENTED CLINICALLY), LIVER * 1	1/153 (0.65%)	1/151 (0.66%)
INFECTION (DOCUMENTED CLINICALLY), LUNG (PNEUMONIA) * 1	3/153 (1.96%)	0/151 (0.00%)
INFECTION (DOCUMENTED CLINICALLY), PERITONEAL CAVITY * 1	2/153 (1.31%)	1/151 (0.66%)
INFECTION (DOCUMENTED CLINICALLY), SKIN (CELLULITIS) * 1	0/153 (0.00%)	2/151 (1.32%)
INFECTION (DOCUMENTED CLINICALLY), UPPER AIRWAY NOS * 1	0/153 (0.00%)	1/151 (0.66%)
INFECTION WITH NORMAL ANC, APPENDIX * 1	1/153 (0.65%)	0/151 (0.00%)
INFECTION WITH NORMAL ANC, BILIARY TREE * 1	1/153 (0.65%)	1/151 (0.66%)
INFECTION WITH NORMAL ANC, BLADDER (URINARY) * 1	0/153 (0.00%)	1/151 (0.66%)
INFECTION WITH NORMAL ANC, BLOOD * 1	4/153 (2.61%)	0/151 (0.00%)
INFECTION WITH NORMAL ANC, LIVER * 1	1/153 (0.65%)	0/151 (0.00%)
INFECTION WITH NORMAL ANC, PERITONEAL CAVITY * 1	1/153 (0.65%)	1/151 (0.66%)
INFECTION WITH NORMAL ANC, SKIN (CELLULITIS) * 1	1/153 (0.65%)	0/151 (0.00%)
INFECTION WITH NORMAL ANC, URINARY TRACT NOS * 1	0/153 (0.00%)	1/151 (0.66%)
INFECTION WITH UNKNOWN ANC, BONE (OSTEOMYELITIS) * 1	1/153 (0.65%)	0/151 (0.00%)
INFECTION WITH UNKNOWN ANC, LUNG (PNEUMONIA) * 1	2/153 (1.31%)	1/151 (0.66%)
INFECTION WITH UNKNOWN ANC, PANCREAS * 1	0/153 (0.00%)	1/151 (0.66%)
Metabolism and nutrition disorders
ALKALINE PHOSPHATASE * 1	1/153 (0.65%)	0/151 (0.00%)
ALT * 1	6/153 (3.92%)	0/151 (0.00%)
AMYLASE * 1	1/153 (0.65%)	0/151 (0.00%)
AST * 1	7/153 (4.58%)	0/151 (0.00%)
BILIRUBIN (HYPERBILIRUBINEMIA) * 1	5/153 (3.27%)	1/151 (0.66%)
CREATININE * 1	0/153 (0.00%)	1/151 (0.66%)
HYPERGLYCEMIA * 1	0/153 (0.00%)	1/151 (0.66%)
HYPOGLYCEMIA * 1	1/153 (0.65%)	0/151 (0.00%)
LIPASE * 1	2/153 (1.31%)	2/151 (1.32%)
METABOLIC/LAB - OTHER * 1	0/153 (0.00%)	1/151 (0.66%)
Musculoskeletal and connective tissue disorders
FRACTURE * 1	0/153 (0.00%)	2/151 (1.32%)
JOINT-FUNCTION * 1	0/153 (0.00%)	1/151 (0.66%)
MUSCLE WEAKNESS, LEFT-SIDED * 1	0/153 (0.00%)	1/151 (0.66%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SECONDARY MALIGNANCY (POSSIBLY RELATED TO CANCER TREATMENT) * 1	1/153 (0.65%)	1/151 (0.66%)
Nervous system disorders
COGNITIVE DISTURBANCE * 1	1/153 (0.65%)	0/151 (0.00%)
CONFUSION * 1	0/153 (0.00%)	1/151 (0.66%)
ENCEPHALOPATHY * 1	6/153 (3.92%)	1/151 (0.66%)
SEIZURE * 1	1/153 (0.65%)	0/151 (0.00%)
Renal and urinary disorders
OBSTRUCTION, GU, PROSTATE * 1	0/153 (0.00%)	1/151 (0.66%)
RENAL - OTHER * 1	0/153 (0.00%)	1/151 (0.66%)
RENAL FAILURE * 1	1/153 (0.65%)	3/151 (1.99%)
URINARY RETENTION * 1	1/153 (0.65%)	0/151 (0.00%)
Respiratory, thoracic and mediastinal disorders
ARDS * 1	1/153 (0.65%)	0/151 (0.00%)
DYSPNEA (SHORTNESS OF BREATH) * 1	3/153 (1.96%)	1/151 (0.66%)
PNEUMONITIS * 1	0/153 (0.00%)	1/151 (0.66%)
PULMONARY - OTHER * 1	1/153 (0.65%)	0/151 (0.00%)
Skin and subcutaneous tissue disorders
RASH/DESQUAMATION * 1	1/153 (0.65%)	0/151 (0.00%)
ULCERATION * 1	0/153 (0.00%)	1/151 (0.66%)
Vascular disorders
ARTERY INJURY, EXTREMITY - LOWER * 1	1/153 (0.65%)	1/151 (0.66%)
ARTERY INJURY, OTHER NOS * 1	1/153 (0.65%)	0/151 (0.00%)
HEMORRHAGE PULMONARY, BRONCHOPULMONARY NOS * 1	1/153 (0.65%)	0/151 (0.00%)
HEMORRHAGE WITH SURGERY * 1	1/153 (0.65%)	1/151 (0.66%)
HEMORRHAGE, GI, ABDOMEN NOS * 1	2/153 (1.31%)	1/151 (0.66%)
HEMORRHAGE, GI, ESOPHAGUS * 1	1/153 (0.65%)	0/151 (0.00%)
HEMORRHAGE, GI, LIVER * 1	1/153 (0.65%)	0/151 (0.00%)
HEMORRHAGE, GI, LOWER GI NOS * 1	2/153 (1.31%)	0/151 (0.00%)
HEMORRHAGE, GI, PERITONEAL CAVITY * 1	0/153 (0.00%)	2/151 (1.32%)
HEMORRHAGE, GI, RECTUM * 1	1/153 (0.65%)	0/151 (0.00%)
HEMORRHAGE, GI, STOMACH * 1	3/153 (1.96%)	1/151 (0.66%)
HEMORRHAGE, GI, UPPER GI NOS * 1	1/153 (0.65%)	2/151 (1.32%)
HEMORRHAGE, GI, VARICES (ESOPHAGEAL) * 1	3/153 (1.96%)	4/151 (2.65%)
HEMORRHAGE, GI, VARICES (RECTAL) * 1	1/153 (0.65%)	0/151 (0.00%)
PERIPHERAL ARTERIAL ISCHEMIA * 1	1/153 (0.65%)	0/151 (0.00%)
THROMBOSIS/THROMBUS/EMBOLISM * 1	1/153 (0.65%)	0/151 (0.00%)
VASCULAR - OTHER * 1	1/153 (0.65%)	0/151 (0.00%)
VISCERAL ARTERIAL ISCHEMIA * 1	2/153 (1.31%)	2/151 (1.32%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, NCI-CTCAE v.3.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Sorafenib (Nexavar, BAY43-9006) + TACE	Placebo + TACE
	Affected / at Risk (%)	Affected / at Risk (%)
Total	150/153 (98.04%)	139/151 (92.05%)
Blood and lymphatic system disorders
EDEMA: LIMB * 1	7/153 (4.58%)	16/151 (10.60%)
HEMOGLOBIN * 1	13/153 (8.50%)	9/151 (5.96%)
PLATELETS * 1	16/153 (10.46%)	3/151 (1.99%)
Cardiac disorders
HYPERTENSION * 1	46/153 (30.07%)	27/151 (17.88%)
Endocrine disorders
DIABETES * 1	0/153 (0.00%)	8/151 (5.30%)
Gastrointestinal disorders
ANOREXIA * 1	48/153 (31.37%)	31/151 (20.53%)
ASCITES * 1	25/153 (16.34%)	22/151 (14.57%)
CONSTIPATION * 1	29/153 (18.95%)	27/151 (17.88%)
DIARRHEA * 1	81/153 (52.94%)	28/151 (18.54%)
DISTENSION * 1	10/153 (6.54%)	11/151 (7.28%)
GASTRITIS * 1	10/153 (6.54%)	7/151 (4.64%)
GI - OTHER * 1	16/153 (10.46%)	13/151 (8.61%)
HEARTBURN * 1	5/153 (3.27%)	10/151 (6.62%)
MUCOSITIS (FUNCTIONAL/SYMPTOMATIC), ORAL CAVITY * 1	16/153 (10.46%)	6/151 (3.97%)
NAUSEA * 1	59/153 (38.56%)	58/151 (38.41%)
VOMITING * 1	27/153 (17.65%)	40/151 (26.49%)
General disorders
FATIGUE * 1	65/153 (42.48%)	50/151 (33.11%)
FEVER * 1	56/153 (36.60%)	49/151 (32.45%)
FLU-LIKE SYNDROME * 1	6/153 (3.92%)	12/151 (7.95%)
INSOMNIA * 1	19/153 (12.42%)	23/151 (15.23%)
PAIN, ABDOMEN NOS * 1	93/153 (60.78%)	91/151 (60.26%)
PAIN, BACK * 1	12/153 (7.84%)	14/151 (9.27%)
PAIN, CHEST/THORAX NOS * 1	9/153 (5.88%)	6/151 (3.97%)
PAIN, EXTREMITY-LIMB * 1	6/153 (3.92%)	8/151 (5.30%)
PAIN, HEAD/HEADACHE * 1	13/153 (8.50%)	6/151 (3.97%)
PAIN, JOINT * 1	13/153 (8.50%)	15/151 (9.93%)
PAIN, LIVER * 1	6/153 (3.92%)	11/151 (7.28%)
PAIN, MUSCLE * 1	18/153 (11.76%)	11/151 (7.28%)
PAIN, STOMACH * 1	7/153 (4.58%)	11/151 (7.28%)
RIGORS/CHILLS * 1	11/153 (7.19%)	6/151 (3.97%)
WEIGHT LOSS * 1	31/153 (20.26%)	16/151 (10.60%)
Metabolism and nutrition disorders
ALT * 1	22/153 (14.38%)	25/151 (16.56%)
AMYLASE * 1	8/153 (5.23%)	9/151 (5.96%)
AST * 1	34/153 (22.22%)	29/151 (19.21%)
BILIRUBIN (HYPERBILIRUBINEMIA) * 1	21/153 (13.73%)	13/151 (8.61%)
HYPERGLYCEMIA * 1	8/153 (5.23%)	15/151 (9.93%)
HYPOALBUMINEMIA * 1	19/153 (12.42%)	10/151 (6.62%)
HYPOKALEMIA * 1	16/153 (10.46%)	4/151 (2.65%)
HYPOPHOSPHATEMIA * 1	8/153 (5.23%)	2/151 (1.32%)
LIPASE * 1	18/153 (11.76%)	12/151 (7.95%)
METABOLIC/LAB - OTHER * 1	8/153 (5.23%)	6/151 (3.97%)
Nervous system disorders
DIZZINESS * 1	12/153 (7.84%)	5/151 (3.31%)
MOOD ALTERATION, ANXIETY * 1	8/153 (5.23%)	12/151 (7.95%)
Renal and urinary disorders
URINARY FREQUENCY * 1	8/153 (5.23%)	6/151 (3.97%)
Respiratory, thoracic and mediastinal disorders
COUGH * 1	21/153 (13.73%)	13/151 (8.61%)
DYSPNEA (SHORTNESS OF BREATH) * 1	13/153 (8.50%)	8/151 (5.30%)
VOICE CHANGES * 1	9/153 (5.88%)	4/151 (2.65%)
Skin and subcutaneous tissue disorders
ALOPECIA * 1	43/153 (28.10%)	11/151 (7.28%)
DERMATOLOGY - OTHER * 1	11/153 (7.19%)	7/151 (4.64%)
DRY SKIN * 1	16/153 (10.46%)	6/151 (3.97%)
HAND-FOOT SKIN REACTION * 1	71/153 (46.41%)	10/151 (6.62%)
PRURITUS * 1	13/153 (8.50%)	18/151 (11.92%)
RASH/DESQUAMATION * 1	33/153 (21.57%)	11/151 (7.28%)
Vascular disorders
HEMORRHAGE PULMONARY, NOSE * 1	8/153 (5.23%)	5/151 (3.31%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, NCI-CTCAE v.3.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The investigator must discuss and obtain written consent of the sponsor on the intended publication. The investigator must send a draft manuscript of the publication or abstract to the sponsor thirty days in advance of the submission inorder to obtain approval.

Results Point of Contact

• Name/Title: Therapeutic Area Head
• Organization: BAYER
• EMail: clinical-trial-contact@bayerhealthcare.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lencioni R, Llovet JM, Han G, Tak WY, Yang J, Guglielmi A, Paik SW, Reig M, Kim DY, Chau GY, Luca A, Del Arbol LR, Leberre MA, Niu W, Nicholson K, Meinhardt G, Bruix J. Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: The SPACE trial. J Hepatol. 2016 May;64(5):1090-1098. doi: 10.1016/j.jhep.2016.01.012. Epub 2016 Jan 22.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT00855218
• Other Study ID Numbers: 12918; 2008-005056-24 ( EudraCT Number )
• First Submitted: March 3, 2009
• First Posted: March 4, 2009
• Results First Submitted: August 23, 2012
• Results First Posted: September 24, 2012
• Last Update Posted: August 18, 2017