A Research Study to Treat Patients With Advanced Hepatocellular Carcinoma - Study Results

Study Type:	Interventional
Study Design:	Randomized, Double-Blind, Placebo Control, Parallel Assignment
Condition:	Carcinoma, Hepatocellular
Interventions:	Drug: Sorafenib (Nexavar, BAY43-9006) plus Doxorubicin Drug: Doxorubicin/Placebo

Participant Flow

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 ITT population (primary population for 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 (Nexavar, BAY43-9006) plus Doxorubicin
Placebo + Doxorubicin	Placebo plus Doxorubicin

Participant Flow for 2 periods

Period: Treatment

	Sorafenib + Doxorubicin	Placebo + Doxorubicin
STARTED	47^[1]	49^[2]
COMPLETED	47^[3]	49^[4]
NOT COMPLETED	0	0

[1]	ITT population
[2]	ITT population
[3]	No patient under study medication anymore
[4]	No patient under study medication anymore

Period: 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 (Nexavar, BAY43-9006) plus Doxorubicin
Placebo + Doxorubicin	Placebo plus Doxorubicin

Baseline Measures

	Sorafenib + Doxorubicin	Placebo + Doxorubicin	Total
Number of Participants [units: participants]	47	49	96
Age [units: years] 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
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]	The ECOG PS is an expert rating of cancer patients' daily living abilities, from 0 to 5. 0=Fully active, able to carry on all pre-disease performance without restriction. 3=Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours. 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 [ until progression occured ]

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2. Secondary:

Overall Survival [ until death occurred ]

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3. Secondary:

Progression Free Survival [ until progression or death occurred ]

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4. Secondary:

Overall Best Tumor Response Rate [ achieved during treatment or within 30 days after termination of active therapy ]

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5. Secondary:

Time to Symptomatic Progression [ until first documented symptomatic progression defined by FHSI-8 assessment ]

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6. Secondary:

Duration of Response [ from first objective response to progression ]

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7. Secondary:

Time to Response [ from randomization to first objective response ]

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8. Secondary:

Overall Disease Control Rate (DCR) [ from 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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Time Frame	No text entered.
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Frequency Threshold

Threshold above which other adverse events are reported	20%

Reporting Groups

	Description
Sorafenib + Doxorubicin	Sorafenib (Nexavar, BAY43-9006) plus Doxorubicin
Placebo + Doxorubicin	Placebo plus Doxorubicin

Other Adverse Events

	Sorafenib + Doxorubicin	Placebo + Doxorubicin
Total, other (not including serious) adverse events
# participants affected	47	44
Blood and lymphatic system disorders
Neutrophils * ^A # participants affected / at risk	31/47 (65.96%)	29/48 (60.42%)
Hemoglobin * ^A # participants affected / at risk	15/47 (31.91%)	14/48 (29.17%)
Leukocytes * ^A # participants affected / at risk	10/47 (21.28%)	9/48 (18.75%)
Edema: Limb * ^A # participants affected / at risk	15/47 (31.91%)	13/48 (27.08%)
Gastrointestinal disorders
Nausea * ^A # participants affected / at risk	27/47 (57.45%)	27/48 (56.25%)
Constipation * ^A # participants affected / at risk	21/47 (44.68%)	21/48 (43.75%)
Anorexia * ^A # participants affected / at risk	24/47 (51.06%)	14/48 (29.17%)
Diarrhea * ^A # participants affected / at risk	25/47 (53.19%)	12/48 (25.00%)
Mucositis (Functional/Symptomatic), Oral Cavity * ^A # participants affected / at risk	11/47 (23.40%)	14/48 (29.17%)
GI - other * ^A # participants affected / at risk	13/47 (27.66%)	7/48 (14.58%)
Mucositis (Clinical Exam), Oral Cavity * ^A # participants affected / at risk	10/47 (21.28%)	6/48 (12.50%)
Taste Alteration * ^A # participants affected / at risk	10/47 (21.28%)	5/48 (10.42%)
Vomiting * ^A # participants affected / at risk	17/47 (36.17%)	10/48 (20.83%)
General disorders
Fatique * ^A # participants affected / at risk	39/47 (82.98%)	32/48 (66.67%)
Insomnia * ^A # participants affected / at risk	13/47 (27.66%)	8/48 (16.67%)
Pain, Abdomen NOS * ^A # participants affected / at risk	18/47 (38.30%)	14/48 (29.17%)
Pain, Back * ^A # participants affected / at risk	14/47 (29.79%)	7/48 (14.58%)
Metabolism and nutrition disorders
Bilirubin (Hyperbilirubinemia) * ^A # participants affected / at risk	15/47 (31.91%)	15/48 (31.25%)
AST * ^A # participants affected / at risk	11/47 (23.40%)	7/48 (14.58%)
Nervous system disorders
Dizziness * ^A # participants affected / at risk	10/47 (21.28%)	3/48 (6.25%)
Respiratory, thoracic and mediastinal disorders
Cough * ^A # participants affected / at risk	13/47 (27.66%)	9/48 (18.75%)
Skin and subcutaneous tissue disorders
Alopecia * ^A # participants affected / at risk	24/47 (51.06%)	25/48 (52.08%)
Rash/Desquamation * ^A # participants affected / at risk	18/47 (38.30%)	8/48 (16.67%)
Hand-Foot Skin Reaction * ^A # participants affected / at risk	14/47 (29.79%)	2/48 (4.17%)
Dry Skin * ^A # participants affected / at risk	10/47 (21.28%)	4/48 (8.33%)

*	Indicates events were collected by non-systematic assessment.
^A	Term from vocabulary, NCI CTC V3

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

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