A Research Study to Treat Patients With Advanced Hepatocellular Carcinoma

This study has been completed.

Study NCT00108953 Information provided by Bayer

First Received on April 21, 2005. Last Updated on March 11, 2011 History of Changes

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; 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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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)

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 ]

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2. Secondary:

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

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3. Secondary:

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

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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 ]

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5. Secondary:

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

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6. Secondary:

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

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7. Secondary:

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

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8. Secondary:

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

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The institution of the Coordinating Investigator (CI) has the right, consistent with academic standards, to publish any proposed publication written by the consultant as part of their services under this agreement. If the sponsor believes that any proposed publication contained any confidential information, the sponsor shall notify the CI, and the CI shall remove such confidential information.

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
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.

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:

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.

Responsible Party:	Therapeutic Area Head, Bayer HealthCare AG
ClinicalTrials.gov Identifier:	NCT00108953 History of Changes
Other Study ID Numbers:	11546, EudraCT: 2004-001770-40
Study First Received:	April 21, 2005
Results First Received:	April 23, 2009
Last Updated:	March 11, 2011
Health Authority:	United States: Food and Drug Administration