Back to resultsA 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).
Primary Purpose
Carcinoma, Hepatocellular
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Sorafenib (Nexavar, BAY43-9006)
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Hepatocellular focused on measuring Sorafenib, TACE, DC bead, Combination
Eligibility Criteria
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.
Sites / Locations
- Abbott Northwestern Hospital
- Gangnam Severance Hospital, Yonsei University
- Hospital Central de Asturias
- Fundación Hospital Alcorcón
- Hospital Universitario Virgen del Rocío
- Changhua Christian Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Sorafenib (Nexavar, BAY43-9006) + TACE
Placebo + TACE
Arm Description
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.)
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.)
Outcomes
Primary Outcome Measures
Time to Progression (TTP) - Independent Radiological Review (Primary Analysis)
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
Overall Survival (OS)
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 to Untreatable Progression (TTUP)
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 to Vascular Invasion/Extrahepatic Spread (TTVI/ES)
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.
Tumor Response - Independent Radiological Review
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.
Tumor Response - Investigator Assessment
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00855218
Brief 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).
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 Type
Interventional
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
February 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Hepatocellular
Keywords
Sorafenib, TACE, DC bead, Combination
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
307 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sorafenib (Nexavar, BAY43-9006) + TACE
Arm Type
Experimental
Arm Description
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.)
Arm Title
Placebo + TACE
Arm Type
Placebo Comparator
Arm Description
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.)
Intervention Type
Drug
Intervention Name(s)
Sorafenib (Nexavar, BAY43-9006)
Intervention Description
800 mg sorafenib (4 tablets) will be taken daily (400mg b.i.d. [twice daily], 2 tablets). Transarterial Chemoembolization (TACE) using DC Bead
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
4 tablets of placebo will be taken daily (2 tablets b.i.d). TACE using DC Bead
Primary Outcome Measure Information:
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)
Secondary Outcome Measure Information:
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)
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)
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)
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)
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-7077
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610-0316
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309-1231
Country
United States
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0330
Country
United States
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Abbott Northwestern Hospital
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210-1240
Country
United States
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23249
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1023
Country
United States
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
City
St Leonards
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
City
Greenslopes
State/Province
Queensland
ZIP/Postal Code
4120
Country
Australia
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
City
Innsbruck
ZIP/Postal Code
6020
Country
Austria
City
Wien
ZIP/Postal Code
1090
Country
Austria
City
Bruxelles - Brussel
ZIP/Postal Code
1070
Country
Belgium
City
Bruxelles - Brussel
ZIP/Postal Code
1090
Country
Belgium
City
Bruxelles - Brussel
ZIP/Postal Code
1200
Country
Belgium
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
City
Liege
ZIP/Postal Code
4000
Country
Belgium
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N1
Country
Canada
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 2Y9
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2N2
Country
Canada
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China
City
Xi'an
State/Province
Shannxi
ZIP/Postal Code
710032
Country
China
City
Beijing
ZIP/Postal Code
100021
Country
China
City
Beijing
ZIP/Postal Code
100142
Country
China
City
Shanghai
ZIP/Postal Code
200032
Country
China
City
Shanghai
ZIP/Postal Code
200438
Country
China
City
Creteil
ZIP/Postal Code
94010
Country
France
City
Lille
ZIP/Postal Code
59037
Country
France
City
Lyon Cedex
ZIP/Postal Code
69288
Country
France
City
Lyon
ZIP/Postal Code
69003
Country
France
City
Marseille
ZIP/Postal Code
13005
Country
France
City
Paris
ZIP/Postal Code
75020
Country
France
City
Paris
ZIP/Postal Code
75571
Country
France
City
Vandoeuvre-les-nancy
ZIP/Postal Code
54500
Country
France
City
Villejuif
ZIP/Postal Code
94800
Country
France
City
Villejuif
ZIP/Postal Code
94805
Country
France
City
Freiburg
State/Province
Baden-Württemberg
ZIP/Postal Code
79106
Country
Germany
City
Heidelberg
State/Province
Baden-Württemberg
ZIP/Postal Code
69120
Country
Germany
City
Tübingen
State/Province
Baden-Württemberg
ZIP/Postal Code
72076
Country
Germany
City
Erlangen
State/Province
Bayern
ZIP/Postal Code
91054
Country
Germany
City
München
State/Province
Bayern
ZIP/Postal Code
81377
Country
Germany
City
Regensburg
State/Province
Bayern
ZIP/Postal Code
93042
Country
Germany
City
Frankfurt
State/Province
Hessen
ZIP/Postal Code
60590
Country
Germany
City
Hannover
State/Province
Niedersachsen
ZIP/Postal Code
30625
Country
Germany
City
Essen
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
45136
Country
Germany
City
Essen
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
45147
Country
Germany
City
Münster
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
48149
Country
Germany
City
Mainz
State/Province
Rheinland-Pfalz
ZIP/Postal Code
55131
Country
Germany
City
Homburg
State/Province
Saarland
ZIP/Postal Code
66421
Country
Germany
City
Jena
State/Province
Thüringen
ZIP/Postal Code
07743
Country
Germany
City
Berlin
ZIP/Postal Code
13353
Country
Germany
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
City
Napoli
State/Province
Campania
ZIP/Postal Code
80131
Country
Italy
City
Bologna
State/Province
Emilia-Romagna
ZIP/Postal Code
40138
Country
Italy
City
Roma
State/Province
Lazio
ZIP/Postal Code
00133
Country
Italy
City
Roma
State/Province
Lazio
ZIP/Postal Code
00185
Country
Italy
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20122
Country
Italy
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20133
Country
Italy
City
Torino
State/Province
Piemonte
ZIP/Postal Code
10126
Country
Italy
City
Bari
State/Province
Puglia
ZIP/Postal Code
70021
Country
Italy
City
Palermo
State/Province
Sicilia
ZIP/Postal Code
90127
Country
Italy
City
Pisa
State/Province
Toscana
ZIP/Postal Code
56124
Country
Italy
City
Padova
State/Province
Veneto
ZIP/Postal Code
35128
Country
Italy
City
Verona
State/Province
Veneto
ZIP/Postal Code
37134
Country
Italy
City
Daegu
ZIP/Postal Code
700-721
Country
Korea, Republic of
City
Gyeonggi-do
ZIP/Postal Code
411-706
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Facility Name
Gangnam Severance Hospital, Yonsei University
City
Seoul
ZIP/Postal Code
135-720
Country
Korea, Republic of
City
Singapore
ZIP/Postal Code
119228
Country
Singapore
City
Singapore
ZIP/Postal Code
169610
Country
Singapore
City
Santiago de Compostela
State/Province
A Coruña
ZIP/Postal Code
15706
Country
Spain
Facility Name
Hospital Central de Asturias
City
Oviedo
State/Province
Asturias
ZIP/Postal Code
33006
Country
Spain
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
City
Sabadell
State/Province
Barcelona
ZIP/Postal Code
08208
Country
Spain
City
Cruces/Barakaldo
State/Province
Bilbao
ZIP/Postal Code
48903
Country
Spain
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Fundación Hospital Alcorcón
City
Alcorcón
State/Province
Madrid
ZIP/Postal Code
28922
Country
Spain
City
La Laguna
State/Province
Santa Cruz de Tenerife
ZIP/Postal Code
38320
Country
Spain
City
A Coruña
ZIP/Postal Code
15006
Country
Spain
City
Alicante
ZIP/Postal Code
03010
Country
Spain
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
City
Córdoba
ZIP/Postal Code
14004
Country
Spain
City
Madrid
ZIP/Postal Code
28034
Country
Spain
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocío
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
City
Valencia
ZIP/Postal Code
46014
Country
Spain
Facility Name
Changhua Christian Hospital
City
Changhua
ZIP/Postal Code
500
Country
Taiwan
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
City
Taipei
ZIP/Postal Code
11217
Country
Taiwan
12. IPD Sharing Statement
Citations:
PubMed Identifier
26809111
Citation
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.
Results Reference
derived
Links:
URL
http://www.clinicaltrialsregister.eu/
Description
Click here to find information about studies related to Bayer Healthcare products conducted in Europe
Learn more about this trial
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).
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