A Study to Estimate Safety and Efficacy of Bay 43-9006 in the Treatment of Hepatocellular Carcinoma - Study Results

Study Type:	Interventional
Study Design:	Non-Randomized, Open Label, Uncontrolled, Single Group Assignment
Condition:	Carcinoma, Hepatocellular
Intervention:	Drug: Nexavar (Sorafenib, BAY43-9006)

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Only subjects with measurable, histologically or cytologically documented hepatocellur carcinoma (HCC) which was inoperable or who had refused surgery could participate in this study.

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of 147 enrolled patients, 137 received treatment. 10 patients failed screening; reasons were: target lesions identified at baseline (3), liver function tests too high for inclusion (2), prior systemic anticancer treatment (2), creatinine too high for inclusion (1), platelets too low for inclusion (1), diagnosis of HCC not confirmed (1)

	BAY 43-9006 400 mg b.i.d.
STARTED	137
COMPLETED	137
NOT COMPLETED	0

	BAY 43-9006 400 mg b.i.d.
STARTED	137
COMPLETED	135
NOT COMPLETED	2
Lost to Follow-up	2

	BAY 43-9006 400 mg b.i.d.
Number of Participants [units: participants]	137
Age [units: participants]
<=18 years	0
Between 18 and 65 years	84
>=65 years	53
Gender [units: participants]
Female	40
Male	97
Child Pugh Status^[1] [units: participants]
Status A	98
Status B	38
Missing	1
Eastern Cooperative Group performance status (ECOG PS) at study entry^[2] [units: participants]
Grade 0	68
Grade 1	69
Grade 2	0
Grade 3	0
Grade 4	0
Stage of Disease at study entry (TNM Classification)^[3] [units: participants]
Stage 1	0
Stage 2	4
Stage 3	42
Stage 4	91

[1]	The Child-Pugh score is used to assess the prognosis of chronic liver disease, mainly cirrhosis. One of the inclusion criterion for this study was a cirrhotic status of Child Pugh class was A or B. Child Pugh class C were excluded.
[2]	Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) is a scoring system used to quantify cancer patients' general well-being. One of the inclusion criteria for this study was an ECOG PS of 0 or 1.
[3]	TNM (Tumor Nodes, Metastases) is a classification system used for solid tumors. One of the inclusion criterion for this study was inoperable tumor (T2 to T4, any N, M0 or M1 as defined by the tumor nodes metastasis [TNM] classification).

Outcome Measures

1. Primary:

Objective Response Rate [ Until 30 days after termination of active therapy ]

Measure Type	Primary
Measure Title	Objective Response Rate
Measure Description	Objective response rate of sorafenib assessed as the proportion of subjects with confirmed complete or partial response as per modified World Health Organization (WHO) criteria.
Time Frame	Until 30 days after termination of active therapy
Safety Issue	No

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.
Intention to Treat (ITT) analyses were performed on subgroups of patients categorized by baseline characteristics of ECOG Performance Status, Child Pugh status, TNM stage at study entry, prior surgical procedure, hepatitis A and B status, and age.

Reporting Groups

	Description
BAY 43-9006 400 mg b.i.d.	Sorafenib 400 mg administered b.i.d.

Measured Values

	BAY 43-9006 400 mg b.i.d.
Number of Participants Analyzed [units: participants]	137
Objective Response Rate [units: percentage of participants with]
Complete response (CR)	0
Partial response (PR)	2.2
Minor response (MR)	5.8
Stable disease (SD)	54.7
Progressive disease (PD)	13.9
Not available for independent review (NA)	22.6
Not evaluable (NE)	0.7

No statistical analysis provided for Objective Response Rate

2. Secondary:

Duration of Response [ Time from first dose of study drug until disease progression ]

Measure Type	Secondary
Measure Title	Duration of Response
Measure Description	Duration of response was calculated from the first date of receiving study drug until documented progressive disease (PD) in subjects who exhibited an objective response.
Time Frame	Time from first dose of study drug until disease progression
Safety Issue	No

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.
Intention to Treat (ITT) analyses were performed on all treated subjects and for subgroups baseline Child Pugh status (A vs B), ECOG PS (0 vs 1), TNM stage at study entry (II/III vs IV), hepatitis B and C status (positive vs negative). The 3 subjects are censored at time of evaluation. The Median is not estimable so the reported number is biased.

Reporting Groups

	Description
BAY 43-9006 400 mg b.i.d.	Sorafenib 400 mg administered b.i.d.

Measured Values

	BAY 43-9006 400 mg b.i.d.
Number of Participants Analyzed [units: participants]	3
Duration of Response [units: days] Median ( Full Range )	374 ( 369 to 443 )

No statistical analysis provided for Duration of Response

3. Secondary:

Time to Response [ Until objective response occurs ]

Measure Type	Secondary
Measure Title	Time to Response
Measure Description	Time from the first day of receiving study drug to the date the CR or PR was documented (with confirmation).
Time Frame	Until objective response occurs
Safety Issue	No

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.
Intention to Treat (ITT) analyses were performed on all treated subjects and for subgroups such as baseline Child Pugh status (A vs B), ECOG PS (0 vs 1), TNM stage at study entry (II/III vs IV), hepatitis B and hepatitis C status (positive vs negative).

Reporting Groups

	Description
BAY 43-9006 400 mg b.i.d.	Sorafenib 400 mg administered b.i.d.

Measured Values

	BAY 43-9006 400 mg b.i.d.
Number of Participants Analyzed [units: participants]	3
Time to Response [units: days] Median ( 95% Confidence Interval )	144 ( 109 to 245 )

No statistical analysis provided for Time to Response

4. Secondary:

Time to Progression [ Until progression occurs ]

Measure Type	Secondary
Measure Title	Time to Progression
Measure Description	Time from the first date of receiving study drug until the first documented PD.
Time Frame	Until progression occurs
Safety Issue	No

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.
Intention to Treat (ITT) analyses were performed on all treated subjects and for subgroups such as baseline Child Pugh status (A vs B), ECOG PS (0 vs 1), TNM stage at study entry (II/III vs IV), hepatitis B and hepatitis C status (positive vs negative).

Reporting Groups

	Description
BAY 43-9006 400 mg b.i.d.	Sorafenib 400 mg administered b.i.d.

Measured Values

	BAY 43-9006 400 mg b.i.d.
Number of Participants Analyzed [units: participants]	106
Time to Progression [units: days] Median ( 95% Confidence Interval )	167 ( 140 to 284 )

No statistical analysis provided for Time to Progression

5. Secondary:

Duration of Stable Disease [ Until documented PD or response. ]

Measure Type	Secondary
Measure Title	Duration of Stable Disease
Measure Description	Time from the first day of receiving study drug until there was a documented PD or response.
Time Frame	Until documented PD or response.
Safety Issue	No

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.
Intention to Treat (ITT) analyses were performed on all treated subjects and for subgroups such as baseline Child Pugh status (A vs B), ECOG PS (0 vs 1), TNM stage at study entry (II/III vs IV), hepatitis B and hepatitis C status (positive vs negative).

Reporting Groups

	Description
BAY 43-9006 400 mg b.i.d.	Sorafenib 400 mg administered b.i.d.

Measured Values

	BAY 43-9006 400 mg b.i.d.
Number of Participants Analyzed [units: participants]	103
Duration of Stable Disease [units: days] Median ( 95% Confidence Interval )	166 ( 135 to 275 )

No statistical analysis provided for Duration of Stable Disease

6. Secondary:

Time to Minor Response [ Until MR was first documented ]

Measure Type	Secondary
Measure Title	Time to Minor Response
Measure Description	Time from the first day of receiving study drug to the date the MR was first documented (with confirmation).
Time Frame	Until MR was first documented
Safety Issue	No

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.
Intention to Treat (ITT) analyses were performed on all treated subjects and for subgroups such as baseline Child Pugh status (A vs B), ECOG PS (0 vs 1), TNM stage at study entry (II/III vs IV), hepatitis B and hepatitis C status (positive vs negative).

Reporting Groups

	Description
BAY 43-9006 400 mg b.i.d.	Sorafenib 400 mg administered b.i.d.

Measured Values

	BAY 43-9006 400 mg b.i.d.
Number of Participants Analyzed [units: participants]	8
Time to Minor Response [units: days] Median ( 95% Confidence Interval )	84 ( 54 to 168 )

No statistical analysis provided for Time to Minor Response

7. Secondary:

Duration of Minor Response [ Time from MR to PD ]

Measure Type	Secondary
Measure Title	Duration of Minor Response
Measure Description	Time from the date that MR was first documented to the date that PD was first documented.
Time Frame	Time from MR to PD
Safety Issue	No

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.
Intention to Treat (ITT) analyses were performed on all treated subjects and for subgroups such as baseline Child Pugh status (A vs B), ECOG PS (0 vs 1), TNM stage at study entry (II/III vs IV), hepatitis B and hepatitis C status (positive vs negative).

Reporting Groups

	Description
BAY 43-9006 400 mg b.i.d.	Sorafenib 400 mg administered b.i.d.

Measured Values

	BAY 43-9006 400 mg b.i.d.
Number of Participants Analyzed [units: participants]	8
Duration of Minor Response [units: days] Mean ( Full Range )	122 ( 49 to 222 )

No statistical analysis provided for Duration of Minor Response

8. Secondary:

Overall Survival [ Start of treatment to death ]

Measure Type	Secondary
Measure Title	Overall Survival
Measure Description	Time from the first date of receiving study medication to death.
Time Frame	Start of treatment to death
Safety Issue	No

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.
Intention to Treat (ITT) analyses were performed on all treated subjects and for subgroups such as baseline Child Pugh status (A vs B), ECOG PS (0 vs 1), TNM stage at study entry (II/III vs IV), hepatitis B and hepatitis C status (positive vs negative).

Reporting Groups

	Description
BAY 43-9006 400 mg b.i.d.	Sorafenib 400 mg administered b.i.d.

Measured Values

	BAY 43-9006 400 mg b.i.d.
Number of Participants Analyzed [units: participants]	137
Overall Survival [units: days] Median ( 95% Confidence Interval )	280 ( 212 to 340 )

No statistical analysis provided for Overall Survival

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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: Agreement between Sponsor and PI should be reached before publication

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
Subjects had advanced disease and were heavily pretreated. National Cancer Institute-Common Toxicity Criteria (NCI-CTC) was translated to Medical Dictionary for Regulatory Activities (MedDRA) for System Organ Class (SOC) 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 HealtCare Pharmaceuticals ( Therapeutic Area Head )
Study ID Numbers:	10874
Study First Received:	August 30, 2002
Results First Received:	February 20, 2009
Last Updated:	June 19, 2009
ClinicalTrials.gov Identifier:	NCT00044512 History of Changes
Health Authority:	United States: Food and Drug Administration