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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 (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00111007
First received: May 16, 2005
Last updated: October 23, 2014
Last verified: October 2014
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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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.
No text entered.

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).



  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) ]

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

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

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

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) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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.


  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:
unchecked 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.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Therapeutic Area Head
Organization: BAYER
e-mail: clinical-trials-contact@bayerhealthcare.com


Publications of Results:

Responsible Party: Bayer
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: October 23, 2014
Health Authority: United States: Food and Drug Administration