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A Phase III Study of Sorafenib in Patients With Advanced Hepatocellular Carcinoma (SHARP)
This study has been completed.
Study NCT00105443   Information provided by Bayer

First Received on March 14, 2005.   Last Updated on January 26, 2012   History of Changes
Results First Received: December 11, 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)
Drug: 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
Subjects with advanced hepatocellular carcinoma (HCC) were enrolled from Mar 10, 2005 to Apr 11, 2006 at 121 study centers in 21 countries around the Globe.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
After a 28 day screening period (902 subjects), 602 were randomized to Sorafenib (400 mg) twice daily (bid), or matching placebo. Majority of screen failures did not meet inclusion criteria. Efficacy population (intent-to-treat, ITT) was all randomized subjects (602), safety population was all subjects receiving at least 1 dose of study drug (599).

Reporting Groups
  Description
A1) Sorafenib (Nexavar, BAY43-9006) - no Open Label Phase Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily; 2 dose reductions to predefined levels of 400 mg once daily (OD) and 400 mg every other day were permitted for adverse events related to study treatment. Note: Safety Data of participants in the arm presented here are reported in Reporting Groups (RG) RG1 and RG3 in the Safety section.
A2) Sorafenib (Nexavar, BAY43-9006) - With Open Label Phase Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily; 2 dose reductions to predefined levels of 400 mg once daily (OD) and 400 mg every other day were permitted for adverse events related to study treatment. Follow-up / Open Label phase: Subjects on sorafenib who continued the study, continued on the same dose of sorafenib as during the double-blind study Note: Safety Data of participants in the arm presented here are reported in Reporting Groups (RG) RG1 and RG3 in the Safety section.
B1) Placebo - no Open Label Phase

Sorafenib-matching placebo tablets were orally administered twice daily (bid).

Note: Safety Data of participants in the arm presented here are reported in Reporting Groups (RG) RG2 and RG4 in the Safety section.
B2) Placebo First - Then Open Label Sorafenib Treatment Phase

Sorafenib-matching placebo tablets were orally administered twice daily (bid). Follow-up / Open Label phase: Subjects on placebo who chose to switch to sorafenib, received an oral dose of 400 mg (2 x 200 mg tablets) bid; similar to the double-blind study.

Note: Safety Data of participants in the arm presented here are reported in Reporting Groups (RG) RG2, RG4, and RG5 in the Safety section.

Participant Flow for 2 periods

 Period 1:   Double-Blind Treatment
    A1) Sorafenib (Nexavar, BAY43-9006) - no Open Label Phase     A2) Sorafenib (Nexavar, BAY43-9006) - With Open Label Phase     B1) Placebo - no Open Label Phase     B2) Placebo First - Then Open Label Sorafenib Treatment Phase  
STARTED     242     57     256     47  
Received Treatment     240 [1]   57 [2]   255 [3]   47 [4]
COMPLETED     228 [5]   57 [6]   245 [7]   47 [8]
NOT COMPLETED     14     0     11     0  
Adverse Event                 1                 0                 0                 0  
Lost to Follow-up                 0                 0                 1                 0  
Withdrawal by Subject                 8                 0                 7                 0  
Physician Decision                 1                 0                 2                 0  
Radiological and symptomatic progression                 4                 0                 1                 0  
[1] Subjects at Risk/Safety Population - partly in RG1 and RG3 (RG = Reporting Group for Safety Data)
[2] Subjects at Risk/Safety Population - partly in RG1 and RG3
[3] Subjects at Risk/Safety Population - partly in RG2 and RG4
[4] Subjects at Risk/Safety Population - partly in RG2 and RG4 as well as RG5
[5] 228 participants directly switched to the Follow-up (FU) phase only
[6] 47 participants continued with Sorafenib Open Label (OL); 10 first to FU prior to also switch to OL
[7] 245 participants directly switched to the Follow-up (FU) phase
[8] 36 participants switched to Sorafenib Open Label (OL); 11 first to FU prior to also switch to OL

Period 2:   Follow-up and/or Open Label Nexavar
    A1) Sorafenib (Nexavar, BAY43-9006) - no Open Label Phase     A2) Sorafenib (Nexavar, BAY43-9006) - With Open Label Phase     B1) Placebo - no Open Label Phase     B2) Placebo First - Then Open Label Sorafenib Treatment Phase  
STARTED     228 [1]   57 [2]   245 [3]   47 [4]
Follow-up Only (no Open Label Treatment)     228 [5]   0     245 [5]   0  
Open Label Treatment Only (no Follow-up)     0     47 [6]   0     36 [6]
Follow-up First, Then Open Label     0     10     0     11  
COMPLETED     0     0 [7]   0     0 [8]
NOT COMPLETED     228     57     245     47  
Death                 180                 7                 219                 4  
Lost to Follow-up                 14                 0                 10                 0  
Withdrawal by Subject                 24                 3                 13                 4  
Adverse Event                 0                 14                 0                 16  
Physician Decision                 1                 0                 1                 0  
Protocol Violation                 0                 2                 0                 0  
Progression by clinical judgment                 0                 2                 0                 5  
Progression, measurement proven                 0                 3                 0                 3  
Disease progression, recurrence, relapse                 6                 0                 1                 0  
Endpoint record not completed                 2                 2                 1                 2  
Planned switch to OL; record incomplete                 1                 0                 0                 0  
Non-compliant with study medication                 0                 0                 0                 1  
Reached ECOG 4                 0                 1                 0                 1  
Switch to commercial drug                 0                 23                 0                 11  
[1] At start of period, 228 participants directly switched to Follow-up (FU)
[2] At start of period, 47 participants directly switched to Open Label (OL) Sorafenib treatment
[3] At start of period, 245 participants directly switched to Follow-up (FU)
[4] At start of period, 36 participants directly switched to Open Label (OL) Sorafenib treatment
[5] In parallel to "Open Label treatment only" phase
[6] In parallel to "Follow-up only" phase; participants received Sorafenib 400 mg bid
[7] 57 participants in total (47 + 10) received Open Label Sorafenib treatment (Subjects at Risk)
[8] 47 participants in total (36 + 11) received Open Label Sorafenib treatment (Subjects at Risk)



  Baseline Characteristics
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Reporting Groups
  Description
Sorafenib (Nexavar, BAY43-9006) Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily; 2 dose reductions to predefined levels of 400 mg once daily (OD) and 400 mg every other day were permitted for adverse events related to study treatment. Follow-up / Open Label phase: Subjects on sorafenib who continued the study, continued on the same dose of sorafenib as during the double-blind study.
Placebo Sorafenib-matching placebo tablets were orally administered twice daily (bid). Follow-up / Open Label phase: Subjects on placebo who chose to switch to sorafenib, received an oral dose of 400 mg (2 x 200 mg tablets) bid; similar to the double-blind study.

Baseline Measures
    Sorafenib (Nexavar, BAY43-9006)     Placebo     Total  
Number of Participants  
[units: participants]
 		  299     303     602  
Age  
[units: years]
Mean ± Standard Deviation 		  64.9  ± 11.2     66.3  ± 10.2     65.6  ± 10.7  
Gender  
[units: Participants]
 		     
Female     39     39     78  
Male     260     264     524  
Baseline Eastern Cooperative Oncology Group (ECOG) [1]
[units: participants]
 		     
0 = fully active     161     164     325  
1 = restricted in physical activity but ambulatory     114     117     231  
2 = capable of selfcare     24     22     46  
Tumor burden [2]
[units: participants]
 		     
Absent     90     91     181  
Present     209     212     421  
[1] Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) is a scale that measures how cancer affects a patient. The scale ranges from 0 (fully active) to 5 (dead). Subjects entering this study were to have an ECOG score of 0, 1 or 2.
[2] Tumor burden refers to the number of cancer cells, the size of a tumor, or the amount of cancer in the body and is also called the tumor load. Randomization was stratified by "tumor burden" assessment, ie, the presence of either macroscopic vascular invasion as determined by radiological assessment and/or extra-hepatic spread versus none.



  Outcome Measures
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1.  Primary:   Overall Survival (OS)   [ Time Frame: from randomization to death due to any cause until an average 7.2 months later up to the data cut-off date approximately 19 months after start of enrollment ]
  Show Outcome Measure 1

2.  Primary:   Time to Symptomatic Progression (TTSP)   [ Time Frame: from randomization to the first documented symptomatic progression until an average 4.8 months later up to the data cut-off date approximately 19 months after start of enrollment ]
  Show Outcome Measure 2

3.  Secondary:   Time to Progression (TTP)   [ Time Frame: from randomization to disease progression based on radiological assessment until an average 2.8 months later up to the data cut-off date approximately 19 months after start of enrollment ]
  Show Outcome Measure 3

4.  Secondary:   Disease Control (DC)   [ Time Frame: time from randomization to end of treatment up to the data cutoff date approximately 19 months after start of enrollment ]
  Show Outcome Measure 4

5.  Secondary:   Patients Reported Outcome (PRO) by Use of the FACT-Hep Questionnaire   [ Time Frame: from randomization to end of treatment up to the data cutoff date approximately 19 months after start of enrollment ]
  Show Outcome Measure 5

6.  Post-Hoc:   Overall Survival   [ Time Frame: from randomization to death due to any cause until an average 8.5 months later up to the data cut-off date approximately 23 months after start of enrollment ]
  Show Outcome Measure 6

7.  Post-Hoc:   Time to Symptomatic Progression (TTSP)   [ Time Frame: from randomization to the first documented symptomatic progression until an average 5.7 months later up to the data cut-off date approximately 23 months after start of enrollment ]
  Show Outcome Measure 7

8.  Post-Hoc:   Time to Progression (TTP)   [ Time Frame: from randomization to disease progression based on radiological assessment until an average 2.8 months later up to the data cut-off date approximately 23 months after start of enrollment ]
  Show Outcome Measure 8

9.  Post-Hoc:   Disease Control (DC)   [ Time Frame: from randomization to end of treatment up to the data cutoff date approximately 23 months after start of enrollment ]
  Show Outcome Measure 9

10.  Post-Hoc:   Patients Reported Outcome (PRO) by Use of the FACT-Hep Questionnaire   [ Time Frame: from randomization to end of treatment up to the data cutoff date approximately 23 months after start of enrollment ]
  Show Outcome Measure 10


  Serious Adverse Events
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  Other Adverse Events
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  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 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.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Limitations and Caveats
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
No text entered.  


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


No publications provided by Bayer

Publications automatically indexed to this study:
Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378-90.


Responsible Party: Therapeutic Area Head, Bayer HealthCare AG
ClinicalTrials.gov Identifier: NCT00105443     History of Changes
Other Study ID Numbers: 100554, 2004-001773-26
Study First Received: March 14, 2005
Results First Received: December 11, 2009
Last Updated: January 26, 2012
Health Authority: United States: Food and Drug Administration





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