Treatment for Subjects With Unresectable Stage III or Stage IV Melanoma

This study has been completed.

Sponsor:

Collaborator:

Onyx Pharmaceuticals

Information provided by:

Bayer

ClinicalTrials.gov Identifier:

NCT00110994

First received: May 16, 2005

Last updated: May 29, 2012

Last verified: May 2012

History of Changes

Results First Received: January 26, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment
Conditions:	Cancer Melanoma
Interventions:	Drug: Sorafenib (Nexavar, BAY43-9006) Drug: Placebo Drug: Dacarbazine

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
A total of 121 subjects were enrolled at 17 centers in the United States. There were 20 screening failures; 12 subjects did not meet 1 or more entry criteria, 4 subjects withdrew consent before randomization, and 4 subjects were not randomized for other reasons. 101 subjects were randomized between 21 Mar 2005 and 27 Apr 2006.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 101 subjects were randomized (50 to Placebo + Dacarbazine (DTIC) and 51 to Sorafenib + DTIC) and were included in the population valid for intent to treat (ITT) analyses. All randomized subjects received study drug and were included in the population valid for safety analyses.

Reporting Groups

Description

Sorafenib (Nexavar, BAY43-9006) + Dacarbazine

Sorafenib, 2 tablets (200 mg each) orally twice daily (bid) on study days 1-21 + Dacarbazine, 1000 mg/m^2 intravenous on study day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.

Placebo + Dacarbazine

Placebo, 2 tablets orally twice daily on study days 1-21 + Dacarbazine, 1000 mg/m^2 intravenous on study day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.

Participant Flow for 3 periods

Period 1: Double-blind (DB) Treatment

	Sorafenib (Nexavar, BAY43-9006) + Dacarbazine	Placebo + Dacarbazine
STARTED	51 ^[1]	50 ^[1]
Received Treatment	51 ^[2]	50 ^[2]
COMPLETED	9	3
NOT COMPLETED	42	47
Adverse Event	3	0
Death	1	0
Withdrawal by Subject	0	2
Progression by clinical judgement	2	1
Radiological and symptomatic progression	34	41
other reasons	2	3

[1]	ITT population
[2]	Safety population

Period 2: Active Follow-up

	Sorafenib (Nexavar, BAY43-9006) + Dacarbazine	Placebo + Dacarbazine
STARTED	1 ^[1]	2 ^[1]
COMPLETED	0	0
NOT COMPLETED	1	2
Disease progression/recurrence/replace	1	0
Other reasons	0	2

[1]	Subjects discontinued DB treatment with CR, PR and SD entered this period.

Period 3: Long Term Follow-up

	Sorafenib (Nexavar, BAY43-9006) + Dacarbazine	Placebo + Dacarbazine
STARTED	41 ^[1]	47 ^[1]
COMPLETED	22	30
NOT COMPLETED	19	17
Death	19	17

[1]	Subjects discontinued DB treatment with DP entered this period.

Baseline Characteristics

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Reporting Groups

	Description
Sorafenib (Nexavar, BAY43-9006) + Dacarbazine	Sorafenib, 2 tablets (200 mg each) orally twice daily (bid) on study days 1-21 + Dacarbazine, 1000 mg/m^2 intravenous on study day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.
Placebo + Dacarbazine	Placebo, 2 tablets orally twice daily on study days 1-21 + Dacarbazine, 1000 mg/m^2 intravenous on study day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.
Total	Total of all reporting groups

Baseline Measures

	Sorafenib (Nexavar, BAY43-9006) + Dacarbazine	Placebo + Dacarbazine	Total
Number of Participants [units: participants]	51	50	101
Age [units: years] Mean ± Standard Deviation	56.5 ± 12.7	60.1 ± 13.8	58.3 ± 13.3
Age, Customized [units: participants]
<65 years	36	33	69
>=65 and <75 years	11	8	19
>=75 years	4	9	13
Gender [units: participants]
Female	13	17	30
Male	38	33	71
American Joint Committee on Cancer (AJCC) Stage at Study Entry ^[1] [units: participants]
Stage III	2	1	3
Stage IV M1a	3	7	10
Stage IV M1b	18	17	35
Stage IV M1c	28	25	53
Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status ^[2] [units: participants]
Status 0	31	31	62
Status 1	20	19	39
Lactate dehydrogenase (LDH) at study entry ^[3] [units: participants]
Normal	33	29	62
Low	1	2	3
High	12	17	29
Missing	5	2	7

[1]	Stage III: Clinical or radiological evidence of regional metastases (M), in either the lymph nodes or intra-lymphatic. Stage IV: M at any distant site. M1a: M to the skin, subcutaneous tissue, or lymph nodes. M1b: M to the lung. M1c: M to all other visceral sites or at any site associated with an elevated serum lactate dehydrogenase.
[2]	Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale that measures how cancer affects a patient. The scale ranges from 0 (fully active) to 5 (dead). Subjects entering this study must have had an ECOG score of 0 or 1 (restricted in physically strenuous activity but ambulatory).
[3]	Lactate dehydrogenase (LDH) was assessed at study entry as part of a battery of tests to assess liver function. A typical normal range is 105 to 333 Units/Liter (U/L), but may vary across laboratories.

Outcome Measures

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1. Primary:

Progression Free Survival (PFS) [ Time Frame: Time from randomization to documented tumor progression or death (the maximum treatment duration of 71.1 weeks) ]

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2. Secondary:

Overall Survival (OS) [ Time Frame: Time from randomization to death (the maximum treatment duration of 71.1 weeks) ]

Show Outcome Measure 2

3. Secondary:

Number of Participants in Tumor Response Categories [ Time Frame: Every 6 weeks from the start of the treatment until the end of treatment visit with a median of 134 days ]

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4. Secondary:

Time to Progression (TTP) [ Time Frame: Time from randomization to documented tumor progression (median time of 148 days) ]

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5. Secondary:

Duration of Response (DOR) [ Time Frame: Time from initial response to documented tumor progression or death (median time of 188 days) ]

Show Outcome Measure 5

6. Secondary:

Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to the Visit When the Best Tumor Response Was Noted [ Time Frame: Baseline and every 6 weeks from the start of the treatment until the end of treatment visit with a median of 134 days ]

Show Outcome Measure 6

7. Secondary:

Change of European Quality of Life 5-dimensional (EQ-5D) Questionnaire Index Score From Baseline to the Visit at Which Best Response Was First Noted [ Time Frame: Baseline and every 6 weeks from the start of the treatment until the end of treatment visit with a median of 134 days ]

Show Outcome Measure 7

8. Secondary:

Change of European Quality of Life 5-dimensional (EQ-5D) Questionnaire Index Score From Baseline to the End of Treatment [ Time Frame: Baseline and every 6 weeks from the start of the treatment until the end of treatment visit with a median of 134 days ]

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Measure Type	Secondary
Measure Title	Change of European Quality of Life 5-dimensional (EQ-5D) Questionnaire Index Score From Baseline to the End of Treatment
Measure Description	European Quality of Life 5-dimensional (EQ-5D) is a self-administered questionnaire developed to measure health status across 5 dimensions: Mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. Each dimension has 3 levels of response: No problem (1), some problems (2), and extreme problems (3). The five dimensions are summarized into a single score, the EQ‑5D index score, which ranges between 0 and 1, with 0 representing the worst imaginable health state or death and 1 representing perfect health.
Time Frame	Baseline and every 6 weeks from the start of the treatment until the end of treatment visit with a median of 134 days
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.
Change of EQ-5D questionnaire index score was analyzed for the intent to treat (ITT) population, defined as all subjects randomized to treatment.

Reporting Groups

Description

Sorafenib (Nexavar, BAY43-9006) + Dacarbazine

Placebo + Dacarbazine

Measured Values

	Sorafenib (Nexavar, BAY43-9006) + Dacarbazine	Placebo + Dacarbazine
Number of Participants Analyzed [units: participants]	51	50
Change of European Quality of Life 5-dimensional (EQ-5D) Questionnaire Index Score From Baseline to the End of Treatment [units: scores on a scale] Mean ± Standard Deviation	-0.015 ± 0.124	-0.019 ± 0.161

Statistical Analysis 1 for Change of European Quality of Life 5-dimensional (EQ-5D) Questionnaire Index Score From Baseline to the End of Treatment

Groups ^[1]	All groups
Method ^[2]	t-test, 2 sided
P Value ^[3]	0.890

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

9. Secondary:

Change of European Quality of Life Visual Analogue Scale (EQ-VAS) Score From Baseline to the Visit at Which Best Response Was First Noted [ Time Frame: Baseline and every 6 weeks from the start of the treatment until the end of treatment visit with a median of 134 days ]

Show Outcome Measure 9

10. Secondary:

Change of European Quality of Life Visual Analogue Scale (EQ-VAS) Score From Baseline to the End of Treatment [ Time Frame: Baseline and every 6 weeks from the start of the treatment until the end of treatment visit with a median of 134 days ]

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:

	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.

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

Responsible Party:	Therapeutic Area Head, Bayer Healthcare Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:	NCT00110994 History of Changes
Other Study ID Numbers:	11715
Study First Received:	May 16, 2005
Results First Received:	January 26, 2011
Last Updated:	May 29, 2012
Health Authority:	United States: Food and Drug Administration

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