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).

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00855218
• Collaborator: (none)
• Enrollment: 307
• Locations: 107
• Arms: 2
• Duration (Months): 47.1
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will look at whether our drug (sorafenib) in combination with chemotherapy delivered directly into your tumor using beads (DC Bead) will slow the progression of the disease. The beads used with the chemotherapy will slowly release the chemotherapy reducing the adverse effects that normally occur with chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Hepatocellular	Drug: Sorafenib (Nexavar, BAY43-9006); Drug: Placebo	Phase 2

Detailed Description

Safety issues will be reported in Adverse Event section. In addition to the secondary outcome measures, Biomarkers and Patient Report Outcome will also be analyzed as other variables.

Study Design

• Study Type: Interventional
• Actual Enrollment: 307 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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).
• Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: Jul 1, 2011
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sorafenib (Nexavar, BAY43-9006) + TACE Sorafenib was to be orally administered as 2 x 200 mg tablets bid (twice daily). Patients 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.)	Drug: Sorafenib (Nexavar, BAY43-9006); 800 mg sorafenib (4 tablets) will be taken daily (400mg b.i.d. [twice daily], 2 tablets). Transarterial Chemoembolization (TACE) using DC Bead
Placebo Comparator: Placebo + TACE 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, 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.)	Drug: Placebo; 4 tablets of placebo will be taken daily (2 tablets b.i.d). TACE using DC Bead

Outcome Measures

Primary Outcome Measures

1. Time to Progression (TTP) - Independent Radiological Review (Primary Analysis) [From randomization of the first participant until 28 months later (cut-off date)]

   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.

Secondary Outcome Measures

1. Overall Survival (OS) [From randomization of the first participant until 28 months later (cut-off date)]

   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.

2. Time to Untreatable Progression (TTUP) [From randomization of the first participant until 28 months later (cut-off date)]

   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.

3. Time to Vascular Invasion/Extrahepatic Spread (TTVI/ES) [From randomization of the first participant until 28 months later (cut-off date)]

   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.

4. Tumor Response - Independent Radiological Review [From randomization of the first participant until 28 months later (cut-off date)]

   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.

5. Tumor Response - Investigator Assessment [From randomization of the first participant until 28 months later (cut-off date)]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Unresectable, multinodular asymptomatic tumor without vascular invasion or extrahepatic spread

• Confirmed Diagnosis of HCC:

• Cirrhotic subjects: Clinical diagnosis by American Association for the Study of Liver Diseases (AASLD) criteria

• HCC can be defined in cirrhotic subjects by one imaging technique (Computed tomography [CT] scan, Magnetic resonance imaging [MRI], or second generation contrast ultrasound) showing a nodule larger than 2 cm with contrast uptake in the arterial phase and washout in venous or late phases or two imaging techniques showing this radiological behavior for nodules of 1-2 cm in diameter.

• Cytohistological confirmation is required for subjects who do not fulfill these eligibility criteria.

• Non-cirrhotic subjects:

For subjects without cirrhosis, histological or cytological confirmation is mandatory

• Documentation of original biopsy for diagnosis is acceptable

• Child Pugh class A without ascites

• Adequate bone marrow, liver and renal function as assessed by central lab by means of the following laboratory requirements from samples within 7 days prior to randomization:

Exclusion Criteria:

• Patients on a liver transplantation list or with advanced liver disease as defined below:

• Child Pugh B and C

• Active gastrointestinal bleeding

• Encephalopathy

• Ascites

• Lesions having previously been treated with local therapy such as resection of HCC, radiofrequency ablation (RFA), percutaneous ethanol injection (PEI) or cryoablation can not be selected as the target lesions.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		La Jolla	California	United States	92037
2		Los Angeles	California	United States	90095-7077
3		San Francisco	California	United States	94115
4		Gainesville	Florida	United States	32610-0316
5		Miami	Florida	United States	33136
6		Orlando	Florida	United States	32804
7		Atlanta	Georgia	United States	30309-1231
8		Ann Arbor	Michigan	United States	48109-0330
9		Detroit	Michigan	United States	48202
10	Abbott Northwestern Hospital	Minneapolis	Minnesota	United States	55407
11		Saint Louis	Missouri	United States	63104
12		New York	New York	United States	10029
13		Cleveland	Ohio	United States	44195
14		Columbus	Ohio	United States	43210-1240
15		Portland	Oregon	United States	97239
16		Richmond	Virginia	United States	23249
17		Seattle	Washington	United States	98101
18		Seattle	Washington	United States	98109-1023
19		Camperdown	New South Wales	Australia	2050
20		St Leonards	New South Wales	Australia	2065
21		Greenslopes	Queensland	Australia	4120
22		Clayton	Victoria	Australia	3168
23		Heidelberg	Victoria	Australia	3084
24		Melbourne	Victoria	Australia	3004
25		Nedlands	Western Australia	Australia	6009
26		Innsbruck		Austria	6020
27		Wien		Austria	1090
28		Bruxelles - Brussel		Belgium	1070
29		Bruxelles - Brussel		Belgium	1090
30		Bruxelles - Brussel		Belgium	1200
31		Leuven		Belgium	3000
32		Liege		Belgium	4000
33		Calgary	Alberta	Canada	T2N 4N1
34		Halifax	Nova Scotia	Canada	B3H 2Y9
35		Toronto	Ontario	Canada	M5G 2N2
36		Guangzhou	Guangdong	China	510060
37		Guangzhou	Guangdong	China	510080
38		Xi'an	Shannxi	China	710032
39		Beijing		China	100021
40		Beijing		China	100142
41		Shanghai		China	200032
42		Shanghai		China	200438
43		Creteil		France	94010
44		Lille		France	59037
45		Lyon Cedex		France	69288
46		Lyon		France	69003
47		Marseille		France	13005
48		Paris		France	75020
49		Paris		France	75571
50		Vandoeuvre-les-nancy		France	54500
51		Villejuif		France	94800
52		Villejuif		France	94805
53		Freiburg	Baden-Württemberg	Germany	79106
54		Heidelberg	Baden-Württemberg	Germany	69120
55		Tübingen	Baden-Württemberg	Germany	72076
56		Erlangen	Bayern	Germany	91054
57		München	Bayern	Germany	81377
58		Regensburg	Bayern	Germany	93042
59		Frankfurt	Hessen	Germany	60590
60		Hannover	Niedersachsen	Germany	30625
61		Essen	Nordrhein-Westfalen	Germany	45136
62		Essen	Nordrhein-Westfalen	Germany	45147
63		Münster	Nordrhein-Westfalen	Germany	48149
64		Mainz	Rheinland-Pfalz	Germany	55131
65		Homburg	Saarland	Germany	66421
66		Jena	Thüringen	Germany	07743
67		Berlin		Germany	13353
68		Hamburg		Germany	20246
69		Napoli	Campania	Italy	80131
70		Bologna	Emilia-Romagna	Italy	40138
71		Roma	Lazio	Italy	00133
72		Roma	Lazio	Italy	00185
73		Milano	Lombardia	Italy	20122
74		Milano	Lombardia	Italy	20133
75		Torino	Piemonte	Italy	10126
76		Bari	Puglia	Italy	70021
77		Palermo	Sicilia	Italy	90127
78		Pisa	Toscana	Italy	56124
79		Padova	Veneto	Italy	35128
80		Verona	Veneto	Italy	37134
81		Daegu		Korea, Republic of	700-721
82		Gyeonggi-do		Korea, Republic of	411-706
83		Seoul		Korea, Republic of	110-744
84		Seoul		Korea, Republic of	120-752
85		Seoul		Korea, Republic of	135-710
86	Gangnam Severance Hospital, Yonsei University	Seoul		Korea, Republic of	135-720
87		Singapore		Singapore	119228
88		Singapore		Singapore	169610
89		Santiago de Compostela	A Coruña	Spain	15706
90	Hospital Central de Asturias	Oviedo	Asturias	Spain	33006
91		Badalona	Barcelona	Spain	08916
92		Sabadell	Barcelona	Spain	08208
93		Cruces/Barakaldo	Bilbao	Spain	48903
94		Barcelona	Catalunya	Spain	08035
95	Fundación Hospital Alcorcón	Alcorcón	Madrid	Spain	28922
96		La Laguna	Santa Cruz de Tenerife	Spain	38320
97		A Coruña		Spain	15006
98		Alicante		Spain	03010
99		Barcelona		Spain	08036
100		Córdoba		Spain	14004
101		Madrid		Spain	28034
102		Madrid		Spain	28046
103	Hospital Universitario Virgen del Rocío	Sevilla		Spain	41013
104		Valencia		Spain	46014
105	Changhua Christian Hospital	Changhua		Taiwan	500
106		Taipei		Taiwan	10002
107		Taipei		Taiwan	11217

Sponsors and Collaborators

• Bayer

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT00855218
• Other Study ID Numbers: 12918; 2008-005056-24
• First Posted: Mar 4, 2009
• Last Update Posted: Aug 18, 2017
• Last Verified: Jul 1, 2017

• Keywords provided by Bayer: Sorafenib; TACE; DC bead; Combination
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Sorafenib

Study Results

Participant Flow

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

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 Participants	154	153	307
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.5 (11.9)	62.7 (11.9)	62.6 (11.9)
Age, Customized (Number) [Number]
<65 years	77 50%	82 53.6%	159 51.8%
65 - 74 years	52 33.8%	48 31.4%	100 32.6%
>=75 years	25 16.2%	23 15%	48 15.6%
Sex: Female, Male (Count of Participants)
Female	19 12.3%	27 17.6%	46 15%
Male	135 87.7%	126 82.4%	261 85%
Eastern Cooperative Oncology Group (ECOG) performance status at enrollment (Scores on a scale) [Number]
Missing	0	1	1
Grade 0	154	152	306
Number of target lesions (Number) [Number]
1	30 19.5%	31 20.3%	61 19.9%
2	58 37.7%	49 32%	107 34.9%
3	33 21.4%	33 21.6%	66 21.5%
4	12 7.8%	18 11.8%	30 9.8%
5	21 13.6%	22 14.4%	43 14%
Number of non-target lesions (Number) [Number]
0	72 46.8%	73 47.7%	145 47.2%
1	40 26%	39 25.5%	79 25.7%
2	24 15.6%	18 11.8%	42 13.7%
3	7 4.5%	10 6.5%	17 5.5%
4	3 1.9%	6 3.9%	9 2.9%
5	4 2.6%	2 1.3%	6 2%
6	0 0%	1 0.7%	1 0.3%
7	1 0.6%	2 1.3%	3 1%
8	1 0.6%	1 0.7%	2 0.7%
10	1 0.6%	1 0.7%	2 0.7%
14	1 0.6%	0 0%	1 0.3%
Alfa-fetoprotein (Number) [Number]
<400 ng/mL	113 73.4%	112 73.2%	225 73.3%
>/=400 ng/mL	41 26.6%	41 26.8%	82 26.7%
Child pugh classification (Number) [Number]
Missing	0 0%	1 0.7%	1 0.3%
Class A	153 99.4%	152 99.3%	305 99.3%
Class B	1 0.6%	0 0%	1 0.3%
Time of first study medication since initial diagnosis (Months) [Median (Full Range) ]
Median (Full Range) [Months]	1.60	1.91	1.71
Time of first study medication since first progression (Months) [Median (Full Range) ]
Median (Full Range) [Months]	1.45	2.56	1.91
Time of first study medication since most recent progression (Months) [Median (Full Range) ]
Median (Full Range) [Months]	1.02	1.25	1.09

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.)
Measure Participants	154	153
Median (95% Confidence Interval) [Days]	169	166

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sorafenib (Nexavar, BAY43-9006) + TACE, Placebo + TACE
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.797
	Confidence Interval	() 95%; 0.588 to 1.080
	Parameter Dispersion	Type: Value:
	Estimation Comments

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.)
Measure Participants	154	153
Median (95% Confidence Interval) [Days]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sorafenib (Nexavar, BAY43-9006) + TACE, Placebo + TACE
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.295
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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.)
Measure Participants	154	153
Median (95% Confidence Interval) [Days]	95	224

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sorafenib (Nexavar, BAY43-9006) + TACE, Placebo + TACE
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.999
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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.)
Measure Participants	154	153
Median (95% Confidence Interval) [Days]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sorafenib (Nexavar, BAY43-9006) + TACE, Placebo + TACE
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.076
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

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.)
Measure Participants	154	153
Response (CR+PR)	55 35.7%	43 28.1%
Complete Response (CR)	20 13%	17 11.1%
Partial Response (PR)	35 22.7%	26 17%
Stable Disease	52 33.8%	56 36.6%
Progressive Disease	20 13%	36 23.5%
Not assessable	27 17.5%	18 11.8%

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.)
Measure Participants	154	153
Response (CR+PR)	66 42.9%	53 34.6%
Complete Response	21 13.6%	20 13.1%
Partial Response	45 29.2%	33 21.6%
Stable Disease	50 32.5%	57 37.3%
Progressive Disease	16 10.4%	30 19.6%
Not Assessable	22 14.3%	13 8.5%

Adverse Events

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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sorafenib (Nexavar, BAY43-9006) + TACE		Placebo + TACE
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	86/153 (56.2%)		56/151 (37.1%)
Blood and lymphatic system disorders
BLOOD - OTHER	0/153 (0%)		1/151 (0.7%)
EDEMA: LIMB	0/153 (0%)		1/151 (0.7%)
HEMOGLOBIN	4/153 (2.6%)		1/151 (0.7%)
LYMPHOPENIA	1/153 (0.7%)		0/151 (0%)
PLATELETS	1/153 (0.7%)		0/151 (0%)
Cardiac disorders
CARDIAC GENERAL - OTHER	0/153 (0%)		1/151 (0.7%)
CARDIAC ISCHEMIA/INFARCTION	3/153 (2%)		2/151 (1.3%)
CARDIOPULMONARY ARREST	1/153 (0.7%)		0/151 (0%)
HYPERTENSION	0/153 (0%)		1/151 (0.7%)
LEFT VENTRICULAR SYSTOLIC DYSFUNCTION	1/153 (0.7%)		0/151 (0%)
SUPRAVENTRICULAR ARRHYTHMIA, ATRIAL FIBRILLATION	1/153 (0.7%)		0/151 (0%)
Endocrine disorders
DIABETES	2/153 (1.3%)		0/151 (0%)
Gastrointestinal disorders
ASCITES	6/153 (3.9%)		2/151 (1.3%)
CONSTIPATION	1/153 (0.7%)		1/151 (0.7%)
DEHYDRATION	1/153 (0.7%)		0/151 (0%)
DIARRHEA	1/153 (0.7%)		0/151 (0%)
GASTRITIS	1/153 (0.7%)		0/151 (0%)
GI - OTHER	2/153 (1.3%)		0/151 (0%)
HEARTBURN	1/153 (0.7%)		0/151 (0%)
ILEUS	0/153 (0%)		1/151 (0.7%)
LEAK, GI, BILIARY TREE	1/153 (0.7%)		0/151 (0%)
NAUSEA	1/153 (0.7%)		1/151 (0.7%)
PERFORATION, GI, DUODENUM	0/153 (0%)		1/151 (0.7%)
PERFORATION, GI, GALLBLADDER	1/153 (0.7%)		0/151 (0%)
PERFORATION, GI, STOMACH	1/153 (0.7%)		0/151 (0%)
VOMITING	1/153 (0.7%)		2/151 (1.3%)
General disorders
CONSTITUTIONAL SYMPTOMS - OTHER	2/153 (1.3%)		0/151 (0%)
DEATH NOT ASSOCIATED WITH CTCAE TERM, DISEASE PROGRESSION NOS	1/153 (0.7%)		2/151 (1.3%)
DEATH NOT ASSOCIATED WITH CTCAE TERM, MULTI-ORGAN FAILURE	0/153 (0%)		1/151 (0.7%)
DEATH NOT ASSOCIATED WITH CTCAE TERM, SUDDEN DEATH	0/153 (0%)		1/151 (0.7%)
FATIGUE	5/153 (3.3%)		1/151 (0.7%)
FEVER	4/153 (2.6%)		6/151 (4%)
PAIN, ABDOMEN NOS	5/153 (3.3%)		7/151 (4.6%)
PAIN, BACK	1/153 (0.7%)		0/151 (0%)
PAIN, BONE	1/153 (0.7%)		0/151 (0%)
PAIN, CHEST WALL	0/153 (0%)		1/151 (0.7%)
PAIN, GALLBLADDER	0/153 (0%)		1/151 (0.7%)
PAIN, JOINT	1/153 (0.7%)		1/151 (0.7%)
PAIN, PLEURA	0/153 (0%)		1/151 (0.7%)
PAIN, STOMACH	1/153 (0.7%)		0/151 (0%)
SYNDROMES - OTHER	2/153 (1.3%)		2/151 (1.3%)
Hepatobiliary disorders
CHOLECYSTITIS	4/153 (2.6%)		2/151 (1.3%)
HEPATOBILIARY - OTHER	6/153 (3.9%)		4/151 (2.6%)
LIVER DYSFUNCTION	11/153 (7.2%)		5/151 (3.3%)
PANCREATITIS	0/153 (0%)		2/151 (1.3%)
Infections and infestations
INFECTION (DOCUMENTED CLINICALLY), BLADDER (URINARY)	1/153 (0.7%)		0/151 (0%)
INFECTION (DOCUMENTED CLINICALLY), BLOOD	1/153 (0.7%)		2/151 (1.3%)
INFECTION (DOCUMENTED CLINICALLY), BRONCHUS	0/153 (0%)		1/151 (0.7%)
INFECTION (DOCUMENTED CLINICALLY), COLON	0/153 (0%)		1/151 (0.7%)
INFECTION (DOCUMENTED CLINICALLY), LIVER	1/153 (0.7%)		1/151 (0.7%)
INFECTION (DOCUMENTED CLINICALLY), LUNG (PNEUMONIA)	3/153 (2%)		0/151 (0%)
INFECTION (DOCUMENTED CLINICALLY), PERITONEAL CAVITY	2/153 (1.3%)		1/151 (0.7%)
INFECTION (DOCUMENTED CLINICALLY), SKIN (CELLULITIS)	0/153 (0%)		2/151 (1.3%)
INFECTION (DOCUMENTED CLINICALLY), UPPER AIRWAY NOS	0/153 (0%)		1/151 (0.7%)
INFECTION WITH NORMAL ANC, APPENDIX	1/153 (0.7%)		0/151 (0%)
INFECTION WITH NORMAL ANC, BILIARY TREE	1/153 (0.7%)		1/151 (0.7%)
INFECTION WITH NORMAL ANC, BLADDER (URINARY)	0/153 (0%)		1/151 (0.7%)
INFECTION WITH NORMAL ANC, BLOOD	4/153 (2.6%)		0/151 (0%)
INFECTION WITH NORMAL ANC, LIVER	1/153 (0.7%)		0/151 (0%)
INFECTION WITH NORMAL ANC, PERITONEAL CAVITY	1/153 (0.7%)		1/151 (0.7%)
INFECTION WITH NORMAL ANC, SKIN (CELLULITIS)	1/153 (0.7%)		0/151 (0%)
INFECTION WITH NORMAL ANC, URINARY TRACT NOS	0/153 (0%)		1/151 (0.7%)
INFECTION WITH UNKNOWN ANC, BONE (OSTEOMYELITIS)	1/153 (0.7%)		0/151 (0%)
INFECTION WITH UNKNOWN ANC, LUNG (PNEUMONIA)	2/153 (1.3%)		1/151 (0.7%)
INFECTION WITH UNKNOWN ANC, PANCREAS	0/153 (0%)		1/151 (0.7%)
Metabolism and nutrition disorders
ALKALINE PHOSPHATASE	1/153 (0.7%)		0/151 (0%)
ALT	6/153 (3.9%)		0/151 (0%)
AMYLASE	1/153 (0.7%)		0/151 (0%)
AST	7/153 (4.6%)		0/151 (0%)
BILIRUBIN (HYPERBILIRUBINEMIA)	5/153 (3.3%)		1/151 (0.7%)
CREATININE	0/153 (0%)		1/151 (0.7%)
HYPERGLYCEMIA	0/153 (0%)		1/151 (0.7%)
HYPOGLYCEMIA	1/153 (0.7%)		0/151 (0%)
LIPASE	2/153 (1.3%)		2/151 (1.3%)
METABOLIC/LAB - OTHER	0/153 (0%)		1/151 (0.7%)
Musculoskeletal and connective tissue disorders
FRACTURE	0/153 (0%)		2/151 (1.3%)
JOINT-FUNCTION	0/153 (0%)		1/151 (0.7%)
MUSCLE WEAKNESS, LEFT-SIDED	0/153 (0%)		1/151 (0.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SECONDARY MALIGNANCY (POSSIBLY RELATED TO CANCER TREATMENT)	1/153 (0.7%)		1/151 (0.7%)
Nervous system disorders
COGNITIVE DISTURBANCE	1/153 (0.7%)		0/151 (0%)
CONFUSION	0/153 (0%)		1/151 (0.7%)
ENCEPHALOPATHY	6/153 (3.9%)		1/151 (0.7%)
SEIZURE	1/153 (0.7%)		0/151 (0%)
Renal and urinary disorders
OBSTRUCTION, GU, PROSTATE	0/153 (0%)		1/151 (0.7%)
RENAL - OTHER	0/153 (0%)		1/151 (0.7%)
RENAL FAILURE	1/153 (0.7%)		3/151 (2%)
URINARY RETENTION	1/153 (0.7%)		0/151 (0%)
Respiratory, thoracic and mediastinal disorders
ARDS	1/153 (0.7%)		0/151 (0%)
DYSPNEA (SHORTNESS OF BREATH)	3/153 (2%)		1/151 (0.7%)
PNEUMONITIS	0/153 (0%)		1/151 (0.7%)
PULMONARY - OTHER	1/153 (0.7%)		0/151 (0%)
Skin and subcutaneous tissue disorders
RASH/DESQUAMATION	1/153 (0.7%)		0/151 (0%)
ULCERATION	0/153 (0%)		1/151 (0.7%)
Vascular disorders
ARTERY INJURY, EXTREMITY - LOWER	1/153 (0.7%)		1/151 (0.7%)
ARTERY INJURY, OTHER NOS	1/153 (0.7%)		0/151 (0%)
HEMORRHAGE PULMONARY, BRONCHOPULMONARY NOS	1/153 (0.7%)		0/151 (0%)
HEMORRHAGE WITH SURGERY	1/153 (0.7%)		1/151 (0.7%)
HEMORRHAGE, GI, ABDOMEN NOS	2/153 (1.3%)		1/151 (0.7%)
HEMORRHAGE, GI, ESOPHAGUS	1/153 (0.7%)		0/151 (0%)
HEMORRHAGE, GI, LIVER	1/153 (0.7%)		0/151 (0%)
HEMORRHAGE, GI, LOWER GI NOS	2/153 (1.3%)		0/151 (0%)
HEMORRHAGE, GI, PERITONEAL CAVITY	0/153 (0%)		2/151 (1.3%)
HEMORRHAGE, GI, RECTUM	1/153 (0.7%)		0/151 (0%)
HEMORRHAGE, GI, STOMACH	3/153 (2%)		1/151 (0.7%)
HEMORRHAGE, GI, UPPER GI NOS	1/153 (0.7%)		2/151 (1.3%)
HEMORRHAGE, GI, VARICES (ESOPHAGEAL)	3/153 (2%)		4/151 (2.6%)
HEMORRHAGE, GI, VARICES (RECTAL)	1/153 (0.7%)		0/151 (0%)
PERIPHERAL ARTERIAL ISCHEMIA	1/153 (0.7%)		0/151 (0%)
THROMBOSIS/THROMBUS/EMBOLISM	1/153 (0.7%)		0/151 (0%)
VASCULAR - OTHER	1/153 (0.7%)		0/151 (0%)
VISCERAL ARTERIAL ISCHEMIA	2/153 (1.3%)		2/151 (1.3%)
Other (Not Including Serious) Adverse Events
	Sorafenib (Nexavar, BAY43-9006) + TACE		Placebo + TACE
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	150/153 (98%)		139/151 (92.1%)
Blood and lymphatic system disorders
EDEMA: LIMB	7/153 (4.6%)		16/151 (10.6%)
HEMOGLOBIN	13/153 (8.5%)		9/151 (6%)
PLATELETS	16/153 (10.5%)		3/151 (2%)
Cardiac disorders
HYPERTENSION	46/153 (30.1%)		27/151 (17.9%)
Endocrine disorders
DIABETES	0/153 (0%)		8/151 (5.3%)
Gastrointestinal disorders
ANOREXIA	48/153 (31.4%)		31/151 (20.5%)
ASCITES	25/153 (16.3%)		22/151 (14.6%)
CONSTIPATION	29/153 (19%)		27/151 (17.9%)
DIARRHEA	81/153 (52.9%)		28/151 (18.5%)
DISTENSION	10/153 (6.5%)		11/151 (7.3%)
GASTRITIS	10/153 (6.5%)		7/151 (4.6%)
GI - OTHER	16/153 (10.5%)		13/151 (8.6%)
HEARTBURN	5/153 (3.3%)		10/151 (6.6%)
MUCOSITIS (FUNCTIONAL/SYMPTOMATIC), ORAL CAVITY	16/153 (10.5%)		6/151 (4%)
NAUSEA	59/153 (38.6%)		58/151 (38.4%)
VOMITING	27/153 (17.6%)		40/151 (26.5%)
General disorders
FATIGUE	65/153 (42.5%)		50/151 (33.1%)
FEVER	56/153 (36.6%)		49/151 (32.5%)
FLU-LIKE SYNDROME	6/153 (3.9%)		12/151 (7.9%)
INSOMNIA	19/153 (12.4%)		23/151 (15.2%)
PAIN, ABDOMEN NOS	93/153 (60.8%)		91/151 (60.3%)
PAIN, BACK	12/153 (7.8%)		14/151 (9.3%)
PAIN, CHEST/THORAX NOS	9/153 (5.9%)		6/151 (4%)
PAIN, EXTREMITY-LIMB	6/153 (3.9%)		8/151 (5.3%)
PAIN, HEAD/HEADACHE	13/153 (8.5%)		6/151 (4%)
PAIN, JOINT	13/153 (8.5%)		15/151 (9.9%)
PAIN, LIVER	6/153 (3.9%)		11/151 (7.3%)
PAIN, MUSCLE	18/153 (11.8%)		11/151 (7.3%)
PAIN, STOMACH	7/153 (4.6%)		11/151 (7.3%)
RIGORS/CHILLS	11/153 (7.2%)		6/151 (4%)
WEIGHT LOSS	31/153 (20.3%)		16/151 (10.6%)
Metabolism and nutrition disorders
ALT	22/153 (14.4%)		25/151 (16.6%)
AMYLASE	8/153 (5.2%)		9/151 (6%)
AST	34/153 (22.2%)		29/151 (19.2%)
BILIRUBIN (HYPERBILIRUBINEMIA)	21/153 (13.7%)		13/151 (8.6%)
HYPERGLYCEMIA	8/153 (5.2%)		15/151 (9.9%)
HYPOALBUMINEMIA	19/153 (12.4%)		10/151 (6.6%)
HYPOKALEMIA	16/153 (10.5%)		4/151 (2.6%)
HYPOPHOSPHATEMIA	8/153 (5.2%)		2/151 (1.3%)
LIPASE	18/153 (11.8%)		12/151 (7.9%)
METABOLIC/LAB - OTHER	8/153 (5.2%)		6/151 (4%)
Nervous system disorders
DIZZINESS	12/153 (7.8%)		5/151 (3.3%)
MOOD ALTERATION, ANXIETY	8/153 (5.2%)		12/151 (7.9%)
Renal and urinary disorders
URINARY FREQUENCY	8/153 (5.2%)		6/151 (4%)
Respiratory, thoracic and mediastinal disorders
COUGH	21/153 (13.7%)		13/151 (8.6%)
DYSPNEA (SHORTNESS OF BREATH)	13/153 (8.5%)		8/151 (5.3%)
VOICE CHANGES	9/153 (5.9%)		4/151 (2.6%)
Skin and subcutaneous tissue disorders
ALOPECIA	43/153 (28.1%)		11/151 (7.3%)
DERMATOLOGY - OTHER	11/153 (7.2%)		7/151 (4.6%)
DRY SKIN	16/153 (10.5%)		6/151 (4%)
HAND-FOOT SKIN REACTION	71/153 (46.4%)		10/151 (6.6%)
PRURITUS	13/153 (8.5%)		18/151 (11.9%)
RASH/DESQUAMATION	33/153 (21.6%)		11/151 (7.3%)
Vascular disorders
HEMORRHAGE PULMONARY, NOSE	8/153 (5.2%)		5/151 (3.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.