A Treatment Combination for Patients With Unresectable Stage III or Stage IV Melanoma

This study has been completed.

Sponsor:

Collaborator:

Onyx Pharmaceuticals

Information provided by:

Bayer

ClinicalTrials.gov Identifier:

NCT00111007

First received: May 16, 2005

Last updated: May 29, 2012

Last verified: May 2012

History of Changes

Results First Received: January 27, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition:	Melanoma
Interventions:	Drug: Sorafenib (Nexavar, BAY43-9006) Drug: Carboplatin/Paclitaxel 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
The study was conducted from May 4 2005 to Jan 08 2009 (first subject’s first visit to last subject's last visit) at 54 centers in 7 countries: Australia (6), Canada (6), France (6), Germany (10), Netherlands (2), United Kingdom (8), and United States (16).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of 315 screened subjects, 270 were randomized (45 failed screening) and were valid for Intent-To-Treat (ITT) analyses (135 in each treatment group). One subject in each group did not receive treatment: 1 died and 1 withdrew consent. Thus, 268 subjects received treatment (134 in each group) and were valid for the safety analyses.

Reporting Groups

Description

Sorafenib (Nexavar, BAY43-9006)

Sorafenib, 400 mg orally, 2 tablets (200 mg each) bid (bis in die [twice daily]) on Study Days 2 to 19 + Paclitaxel (225 mg/m^2 iv [Intravenous]) and Carboplatin (AUC [area under the curve] 6 iv) 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.

Carboplatin/Paclitaxel (C/P)

Placebo, 2 tablets bid on Study Days 2-19 + Paclitaxel (225 mg/m^2 iv) and Carboplatin (AUC 6 iv) 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)	Carboplatin/Paclitaxel (C/P)
STARTED	135 ^[1]	135 ^[1]
Received Treatment	134 ^[2]	134 ^[2]
COMPLETED	27	24
NOT COMPLETED	108	111
Adverse Event	12	4
Death	5	2
Protocol Violation	0	1
Withdrawal by Subject	6	8
Disease progression/recurrence/relapse	1	0
Relapse	1	0
Progression by clinical judgement	0	2
Radiological and symptomatic progression	83	93
Primary reason with other category	0	1

[1]	ITT population
[2]	Safety population

Period 2: Active Follow-up

	Sorafenib (Nexavar, BAY43-9006)	Carboplatin/Paclitaxel (C/P)
STARTED	6 ^[1]	4 ^[1]
COMPLETED	0	2
NOT COMPLETED	6	2
Adverse Event	1	0
Death	2	0
Disease progression/recurrence/relapse	3	2

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

Period 3: Long Term Follow-up

	Sorafenib (Nexavar, BAY43-9006)	Carboplatin/Paclitaxel (C/P)
STARTED	101 ^[1]	107 ^[1]
COMPLETED	54	62
NOT COMPLETED	47	45
Death	34	39
Lost to Follow-up	1	1
Withdrawal by Subject	0	1
Disease progression/recurrence/relapse	2	1
Missing	10	3

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

Baseline Characteristics

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Reporting Groups

	Description
Sorafenib (Nexavar, BAY43-9006)	Sorafenib, 400 mg orally, 2 tablets (200 mg each) bid (bis in die [twice daily]) on Study Days 2 to 19 + Paclitaxel (225 mg/m^2 iv [Intravenous]) and Carboplatin (AUC [area under the curve] 6 iv) 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.
Carboplatin/Paclitaxel (C/P)	Placebo, 2 tablets bid on Study Days 2-19 + Paclitaxel (225 mg/m^2 iv) and Carboplatin (AUC 6 iv) 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)	Carboplatin/Paclitaxel (C/P)	Total
Number of Participants [units: participants]	135	135	270
Age [units: years] Mean ± Standard Deviation	56.0 ± 12.8	55.1 ± 13.0	55.5 ± 57.0
Age, Customized [units: participants]
<65 years	97	92	189
65 to 74 years	29	39	68
>=75 years	9	4	13
Gender [units: participants]
Female	51	48	99
Male	84	87	171
American Joint Committee on Cancer (AJCC) Stage at Study Entry ^[1] [units: participants]
Stage III or IV M1a	16	11	27
Stage IV M1b	27	31	58
Stage IV M1c	92	93	185
Baseline Eastern Cooperative Oncology Group (ECOG) Performance ^[2] [units: participants]
Status 0	76	70	146
Status 1	59	65	124

[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). 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. Subjects entering this study must have had an ECOG score of 0 or 1 (restricted in physically strenuous activity but ambulatory).

[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). 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. Subjects entering this study must have had an ECOG score of 0 or 1 (restricted in physically strenuous activity but ambulatory).

Outcome Measures

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1. Primary:

Progression Free Survival (PFS) [ Time Frame: Time from randomization to documented tumor progression or death (median time of 124 days) ]

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2. Secondary:

Overall Survival (OS) [ Time Frame: Time from randomization to death (median time of 294 days) ]

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3. Secondary:

Time to Progression (TTP) [ Time Frame: Time from randomization to documented tumor progression (median time of 126 days) ]

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4. Secondary:

Duration of Response (DOR) [ Time Frame: Time from initial response to documented tumor progression or death (median time of 197 days) ]

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5. Secondary:

Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status to the Visit When the Best Tumor Response Was Noted [ Time Frame: baseline and at visit when best response was noted (maximum treatment duration of 68.3 weeks) ]

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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.

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
Metastatic melanoma is notorious for its resistance to chemotherapy. Thus, it is unlikely that inhibition of a single factor or pathway would produce a sustained clinical effect in patients with previously treated, highly refractory disease.

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:	NCT00111007 History of Changes
Obsolete Identifiers:	NCT00262912
Other Study ID Numbers:	11718, 2005-000941-12
Study First Received:	May 16, 2005
Results First Received:	January 27, 2011
Last Updated:	May 29, 2012
Health Authority:	United States: Food and Drug Administration

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