A Research Study to Treat Patients With Advanced Hepatocellular Carcinoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00108953
First received: April 21, 2005
Last updated: March 26, 2014
Last verified: March 2014
Results First Received: April 23, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Carcinoma, Hepatocellular
Interventions: Drug: Sorafenib (Nexavar, BAY43-9006) plus Doxorubicin
Drug: Doxorubicin/Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Enrollment started on 13 Apr 2005 and the last study contact occurred on 11 Apr 2008. The study was conducted at 25 active centers in 6 countries (Argentina, Canada, Hong Kong, Russia, United Kingdom, and United States.)

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
140 patients were screened, with 44 screen failures. The intent-to-treat (ITT) population (primary efficacy analysis) includes all randomized patients (96). The Safety population includes all patients who received at least 1 dose of study drug (95). The study consists of 2 periods: treatment period (not fixed but ended by any event) and follow-up.

Reporting Groups
  Description
Sorafenib + Doxorubicin "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 "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)

Participant Flow for 2 periods

Period 1:   Treatment Period
    Sorafenib + Doxorubicin     Placebo + Doxorubicin  
STARTED     47 [1]   49 [1]
COMPLETED     47 [2]   49 [2]
NOT COMPLETED     0     0  
[1] ITT population
[2] No patient under study medication anymore

Period 2:   Follow-up
    Sorafenib + Doxorubicin     Placebo + Doxorubicin  
STARTED     40 [1]   45 [2]
COMPLETED     11     12  
NOT COMPLETED     29     33  
Death                 18                 26  
Lost to Follow-up                 1                 1  
Study terminated by sponsor                 10                 6  
[1] 40 out of 47 patients were followed after end of double blind treatment
[2] 45 out of 49 patients were followed after end of double blind treatment



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sorafenib + Doxorubicin "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 "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)
Total Total of all reporting groups

Baseline Measures
    Sorafenib + Doxorubicin     Placebo + Doxorubicin     Total  
Number of Participants  
[units: participants]
  47     49     96  
Age  
[units: years]
Median ( Full Range )
     
Median (Full Range)     66  
  ( 38 to 82 )  
  65  
  ( 38 to 81 )  
  65  
  ( 38 to 82 )  
Gender  
[units: participants]
     
Female     16     7     23  
Male     31     42     73  
Child Pugh Status [1]
[units: participants]
     
5 (Child-Pugh A)     30     28     58  
6 (Child-Pugh A)     17     19     36  
7 (Child-Pugh B)     0     2     2  
>7     0     0     0  
Eastern Cooperative Group performance status (ECOG PS) at study entry [2]
[units: participants]
     
Grade 0     22     16     38  
Grade 1     18     25     43  
Grade 2     4     3     7  
Grade 3     0     1     1  
missing     3     4     7  
Tumor burden: Extrahepatic spread [3]
[units: participants]
     
yes     24     32     56  
no     23     17     40  
Tumor burden: Macroscopic vascular invasion [4]
[units: participants]
     
yes     13     16     29  
no     33     32     65  
missing     1     1     2  
[1] The Child-Pugh score is used to classify the stages of liver cirrhosis, based on clinical diagnosis and laboratory tests. Assessment of good operative risk (A) if 5 or 6 points, moderate risk (B) if 7 to 9 points, and poor operative risk (C) if 10 to 15 points. A “C” classification forecasts a survival of less than 12 months.
[2] ECOG PS is a rating of daily living abilities, from 0 to 5. 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.
[3] Tumor spread outside the liver, which describes an aggressive and advanced tumor pattern.
[4] Tumor spread into the blood vessels as determined through radiological assessment (e.g., x-ray, imaging), which describes an aggressive and advanced tumor pattern.



  Outcome Measures
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1.  Primary:   Time to Progression (TTP)   [ Time Frame: from date of randomization of the first patient until 3 years later ]

2.  Secondary:   Overall Survival   [ Time Frame: from date of randomization of the first patient until 3 years later ]

3.  Secondary:   Progression Free Survival (PFS)   [ Time Frame: from date of randomization of the first patient until 3 years later ]

4.  Secondary:   Percentage of Participants in Each Category of Best Tumor Response   [ Time Frame: achieved during treatment or within 30 days after termination of active therapy ]

5.  Secondary:   Time to Symptomatic Progression (TTSP)   [ Time Frame: from date of randomization of the first patient until 3 years later ]

6.  Secondary:   Duration of Response   [ Time Frame: from date of randomization of the first patient until 3 years later ]

7.  Secondary:   Time to Response (TTR)   [ Time Frame: from date of randomization until 3 years later at end of study ]

8.  Secondary:   Percentage of Participants for Whom Disease Control Was Achieved   [ Time Frame: from date of randomization to end of treatment plus 30 days ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The study had been prematurely terminated by the sponsor because positive results were obtained in another Nexavar trial (Phase 3 study 100554 NCT00105443). NCI-CTC was translated to MedDRA for SOCs only.


  More Information
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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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Therapeutic Area Head
Organization: BAYER
e-mail: clinical-trials-contact@bayerhealthcare.com


Publications of Results:

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00108953     History of Changes
Other Study ID Numbers: 11546, 2004-001770-40
Study First Received: April 21, 2005
Results First Received: April 23, 2009
Last Updated: March 26, 2014
Health Authority: United States: Food and Drug Administration