Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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
  Hide Participant Flow

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
  Hide Baseline Characteristics

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 
Overall Participants Analyzed 
[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 
[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.
Baseline Eastern Cooperative Oncology Group (ECOG) Performance [1] 
[Units: Participants]
     
Status 0   76   70   146 
Status 1   59   65   124 
[1] 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
  Show All Outcome Measures

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
  Hide 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.


  More Information
  Hide More Information

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 ( EudraCT Number )
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