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A Research Study to Treat Patients With Advanced Hepatocellular Carcinoma

Primary Purpose

Carcinoma, Hepatocellular

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Sorafenib (Nexavar, BAY43-9006) plus Doxorubicin
Doxorubicin/Placebo
Sponsored by
Bayer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Hepatocellular focused on measuring Cancer, Liver Cancer, Hepatocellular carcinoma, HCC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients who have a life expectancy of at least 12 weeks Patients with advanced HCC (unresectable, and/or metastatic) which has been histologically or cytologically documented Patients must have at least one tumor lesion that meets both of the following criteria: can be accurately measured in at least one dimension according to Response Evaluation Criteria in Solid Tumors (RECIST) has not been previously treated with local therapy Patients who have received local therapy except chemoembolization, such as surgery, radiation therapy, hepatic arterial embolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation are eligible, provided that they either have a target lesion which has not been subjected to local therapy and/or the target lesion(s) within the field of the local therapy has shown an increase of 25% in the size. Local therapy must be completed at least 4 weeks prior to the baseline scan Patients who have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 Exclusion Criteria: Previous or concurrent cancer that is distinct in primary site or histology from HCC, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, and superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated > 3 years prior to entry is permitted History of cardiac disease Serious myocardial dysfunction Active, clinically serious infections Known history of Human Immunodeficiency Virus (HIV) infection Known Central Nervous System (CNS) tumors including metastatic brain disease Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Sorafenib + Doxorubicin

Placebo + Doxorubicin

Arm Description

"Sorafenib + Doxorubicin" -- combination therapy: Sorafenib (Nexavar, BAY43-9006) 200 mg tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks)

"Placebo + Doxorubicin" -- monotherapy: Sorafenib (Nexavar, BAY43-9006) matching placebo tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks)

Outcomes

Primary Outcome Measures

Time to Progression (TTP)
TTP was defined as the time from randomization to radiological disease progression by independent assessment.

Secondary Outcome Measures

Overall Survival
The time from date of randomization to date of death
Progression Free Survival (PFS)
Time from the date of randomization to the date of the first documented radiological progression (as defined per independent central radiological assessment) or death, whichever occurs first
Percentage of Participants in Each Category of Best Tumor Response
Percentage of participants with complete or partial response (CR or PR) confirmed according to Response Evaluation Criteria in Solid Tumors (RECIST) and achieved during treatment or 30 days after end of treatment. CR: disappearance of all clinical and radiological tumor lesions. PR: at least 30% decrease in sum of the longest diameters of tumor lesions. Stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease.
Time to Symptomatic Progression (TTSP)
Time from date of randomization to date of first documented symptomatic progression defined by Functional Assessment of Cancer Therapy Hepatobiliary Symptom Index-8 (FHSI-8) assessment
Duration of Response
Time from date of first objective response (complete response [CR] or partial response [PR]) to date progression is first documented (as defined per independent central radiological assessment) or death, whichever occurs first
Time to Response (TTR)
Time from date of randomization to date of first objective response (complete response [CR] or partial response [PR]) is documented and confirmed according to RECIST criteria
Percentage of Participants for Whom Disease Control Was Achieved
Participants with disease control: those who have as best response complete response (CR), partial response (PR) or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease) according to Response Evaluation Criteria in Solid Tumors (RECIST)

Full Information

First Posted
April 21, 2005
Last Updated
October 24, 2014
Sponsor
Bayer
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1. Study Identification

Unique Protocol Identification Number
NCT00108953
Brief Title
A Research Study to Treat Patients With Advanced Hepatocellular Carcinoma
Official Title
A Randomized Controlled Study of BAY43-9006 in Combination With Doxorubicin Versus Doxorubicin in Patients With Advanced Hepatocellular Carcinoma.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
April 2005 (undefined)
Primary Completion Date
April 2008 (Actual)
Study Completion Date
April 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to evaluate the safety and efficacy of doxorubicin plus sorafenib versus doxorubicin plus placebo in patients with advanced hepatocellular carcinoma (HCC).
Detailed Description
In addition to the key secondary outcome parameters the following parameters will be assessed in an exploratory manner: relative time to progression (TTP), time to symptomatic progression (TTSP), response rate (RR) and overall survival between the 2 study populations. The possible and potential predictive assays of clinical benefit through an assessment of the correlation between the defined baseline characteristics and key clinical endpoints. The safety and tolerability will be assessed in the adverse event section. Doxorubicin pharmacokinetics in HCC patients treated with sorafenib versus placebo will be compared and the pharmacokinetic data will be correlated with doxorubicin-related adverse events (i.e., cardiotoxicity).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Hepatocellular
Keywords
Cancer, Liver Cancer, Hepatocellular carcinoma, HCC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
96 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sorafenib + Doxorubicin
Arm Type
Experimental
Arm Description
"Sorafenib + Doxorubicin" -- combination therapy: Sorafenib (Nexavar, BAY43-9006) 200 mg tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks)
Arm Title
Placebo + Doxorubicin
Arm Type
Active Comparator
Arm Description
"Placebo + Doxorubicin" -- monotherapy: Sorafenib (Nexavar, BAY43-9006) matching placebo tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks)
Intervention Type
Drug
Intervention Name(s)
Sorafenib (Nexavar, BAY43-9006) plus Doxorubicin
Intervention Description
Multi kinase inhibitor plus Chemotherapy
Intervention Type
Drug
Intervention Name(s)
Doxorubicin/Placebo
Intervention Description
Chemotherapy plus Placebo
Primary Outcome Measure Information:
Title
Time to Progression (TTP)
Description
TTP was defined as the time from randomization to radiological disease progression by independent assessment.
Time Frame
from date of randomization of the first patient until 3 years later
Secondary Outcome Measure Information:
Title
Overall Survival
Description
The time from date of randomization to date of death
Time Frame
from date of randomization of the first patient until 3 years later
Title
Progression Free Survival (PFS)
Description
Time from the date of randomization to the date of the first documented radiological progression (as defined per independent central radiological assessment) or death, whichever occurs first
Time Frame
from date of randomization of the first patient until 3 years later
Title
Percentage of Participants in Each Category of Best Tumor Response
Description
Percentage of participants with complete or partial response (CR or PR) confirmed according to Response Evaluation Criteria in Solid Tumors (RECIST) and achieved during treatment or 30 days after end of treatment. CR: disappearance of all clinical and radiological tumor lesions. PR: at least 30% decrease in sum of the longest diameters of tumor lesions. Stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease.
Time Frame
achieved during treatment or within 30 days after termination of active therapy
Title
Time to Symptomatic Progression (TTSP)
Description
Time from date of randomization to date of first documented symptomatic progression defined by Functional Assessment of Cancer Therapy Hepatobiliary Symptom Index-8 (FHSI-8) assessment
Time Frame
from date of randomization of the first patient until 3 years later
Title
Duration of Response
Description
Time from date of first objective response (complete response [CR] or partial response [PR]) to date progression is first documented (as defined per independent central radiological assessment) or death, whichever occurs first
Time Frame
from date of randomization of the first patient until 3 years later
Title
Time to Response (TTR)
Description
Time from date of randomization to date of first objective response (complete response [CR] or partial response [PR]) is documented and confirmed according to RECIST criteria
Time Frame
from date of randomization until 3 years later at end of study
Title
Percentage of Participants for Whom Disease Control Was Achieved
Description
Participants with disease control: those who have as best response complete response (CR), partial response (PR) or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease) according to Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame
from date of randomization to end of treatment plus 30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients who have a life expectancy of at least 12 weeks Patients with advanced HCC (unresectable, and/or metastatic) which has been histologically or cytologically documented Patients must have at least one tumor lesion that meets both of the following criteria: can be accurately measured in at least one dimension according to Response Evaluation Criteria in Solid Tumors (RECIST) has not been previously treated with local therapy Patients who have received local therapy except chemoembolization, such as surgery, radiation therapy, hepatic arterial embolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation are eligible, provided that they either have a target lesion which has not been subjected to local therapy and/or the target lesion(s) within the field of the local therapy has shown an increase of 25% in the size. Local therapy must be completed at least 4 weeks prior to the baseline scan Patients who have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 Exclusion Criteria: Previous or concurrent cancer that is distinct in primary site or histology from HCC, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, and superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated > 3 years prior to entry is permitted History of cardiac disease Serious myocardial dysfunction Active, clinically serious infections Known history of Human Immunodeficiency Virus (HIV) infection Known Central Nervous System (CNS) tumors including metastatic brain disease Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211-1850
Country
United States
City
Orange
State/Province
California
ZIP/Postal Code
92668-3298
Country
United States
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304-1207
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
94121
Country
United States
City
Sylmar
State/Province
California
ZIP/Postal Code
91342
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
City
Lafayette
State/Province
Louisiana
ZIP/Postal Code
70506
Country
United States
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
City
Buenos Aires
State/Province
Ciudad Auton. de Buenos Aires
ZIP/Postal Code
C1264AAA
Country
Argentina
City
Neuquen
State/Province
Neuquén
ZIP/Postal Code
Q8300HDH
Country
Argentina
City
Buenos Aires
Country
Argentina
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
City
Hong Kong
Country
Hong Kong
City
Kazan
ZIP/Postal Code
420111
Country
Russian Federation
City
Kirov
ZIP/Postal Code
610002
Country
Russian Federation
City
Krasnodar
ZIP/Postal Code
350040
Country
Russian Federation
City
Maidstone
State/Province
Kent
ZIP/Postal Code
ME16 9QQ
Country
United Kingdom
City
Bebington
State/Province
Merseyside
ZIP/Postal Code
CH63 4JY
Country
United Kingdom
City
Birmingham
State/Province
West Midlands
ZIP/Postal Code
B15 2TT
Country
United Kingdom
City
London
ZIP/Postal Code
W12 0HS
Country
United Kingdom
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
16908937
Citation
Abou-Alfa GK, Schwartz L, Ricci S, Amadori D, Santoro A, Figer A, De Greve J, Douillard JY, Lathia C, Schwartz B, Taylor I, Moscovici M, Saltz LB. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol. 2006 Sep 10;24(26):4293-300. doi: 10.1200/JCO.2005.01.3441. Epub 2006 Aug 14.
Results Reference
result
PubMed Identifier
21081728
Citation
Abou-Alfa GK, Johnson P, Knox JJ, Capanu M, Davidenko I, Lacava J, Leung T, Gansukh B, Saltz LB. Doxorubicin plus sorafenib vs doxorubicin alone in patients with advanced hepatocellular carcinoma: a randomized trial. JAMA. 2010 Nov 17;304(19):2154-60. doi: 10.1001/jama.2010.1672.
Results Reference
result
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 Research Study to Treat Patients With Advanced Hepatocellular Carcinoma

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