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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) ]
  Show Outcome Measure 1

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 ]
  Show Outcome Measure 3

4.  Secondary:   Time to Progression (TTP)   [ Time Frame: Time from randomization to documented tumor progression (median time of 148 days) ]
  Show Outcome Measure 4

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 ]
  Show Outcome Measure 8

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
  Show Serious Adverse Events


  Other Adverse Events
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Time Frame No text entered.
Additional Description Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), National Cancer Institute (NCI), Not Otherwise Specified (NOS)

Frequency Threshold
Threshold above which other adverse events are reported   5%  

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.

Other Adverse Events
    Sorafenib (Nexavar, BAY43-9006) + Dacarbazine     Placebo + Dacarbazine  
Total, other (not including serious) adverse events      
# participants affected / at risk     49/51     45/50  
Blood and lymphatic system disorders      
platelets * 1    
# participants affected / at risk     30/51 (58.82%)     14/50 (28.00%)  
neutrophils * 1    
# participants affected / at risk     23/51 (45.10%)     9/50 (18.00%)  
hemoglobin * 1    
# participants affected / at risk     18/51 (35.29%)     12/50 (24.00%)  
leukocytes * 1    
# participants affected / at risk     13/51 (25.49%)     7/50 (14.00%)  
lymphopenia * 1    
# participants affected / at risk     3/51 (5.88%)     1/50 (2.00%)  
edema: limb * 1    
# participants affected / at risk     3/51 (5.88%)     0/50 (0.00%)  
Cardiac disorders      
hypertension * 1    
# participants affected / at risk     5/51 (9.80%)     0/50 (0.00%)  
hypotension * 1    
# participants affected / at risk     4/51 (7.84%)     0/50 (0.00%)  
Gastrointestinal disorders      
nausea * 1    
# participants affected / at risk     29/51 (56.86%)     26/50 (52.00%)  
diarrhea * 1    
# participants affected / at risk     29/51 (56.86%)     8/50 (16.00%)  
anorexia * 1    
# participants affected / at risk     17/51 (33.33%)     11/50 (22.00%)  
vomiting * 1    
# participants affected / at risk     15/51 (29.41%)     8/50 (16.00%)  
constipation * 1    
# participants affected / at risk     8/51 (15.69%)     12/50 (24.00%)  
heartburn * 1    
# participants affected / at risk     5/51 (9.80%)     5/50 (10.00%)  
GI - other * 1    
# participants affected / at risk     6/51 (11.76%)     2/50 (4.00%)  
flatulence * 1    
# participants affected / at risk     4/51 (7.84%)     2/50 (4.00%)  
taste alteration * 1    
# participants affected / at risk     5/51 (9.80%)     1/50 (2.00%)  
mucositis (functional / symptomatic), oral cavity * 1    
# participants affected / at risk     5/51 (9.80%)     0/50 (0.00%)  
dry mouth * 1    
# participants affected / at risk     3/51 (5.88%)     0/50 (0.00%)  
General disorders      
fatigue * 1    
# participants affected / at risk     29/51 (56.86%)     27/50 (54.00%)  
weight loss * 1    
# participants affected / at risk     9/51 (17.65%)     4/50 (8.00%)  
rigors / chills * 1    
# participants affected / at risk     5/51 (9.80%)     3/50 (6.00%)  
sweating * 1    
# participants affected / at risk     5/51 (9.80%)     2/50 (4.00%)  
fever * 1    
# participants affected / at risk     2/51 (3.92%)     3/50 (6.00%)  
pain, head / headache * 1    
# participants affected / at risk     10/51 (19.61%)     7/50 (14.00%)  
pain, joint * 1    
# participants affected / at risk     11/51 (21.57%)     2/50 (4.00%)  
pain, muscle * 1    
# participants affected / at risk     6/51 (11.76%)     4/50 (8.00%)  
pain, extremity - limb * 1    
# participants affected / at risk     3/51 (5.88%)     1/50 (2.00%)  
pain, pain NOS * 1    
# participants affected / at risk     3/51 (5.88%)     1/50 (2.00%)  
pain, other * 1    
# participants affected / at risk     3/51 (5.88%)     0/50 (0.00%)  
Immune system disorders      
allergic reaction * 1    
# participants affected / at risk     3/51 (5.88%)     0/50 (0.00%)  
Metabolism and nutrition disorders      
lipase * 1    
# participants affected / at risk     13/51 (25.49%)     8/50 (16.00%)  
ALT * 1    
# participants affected / at risk     6/51 (11.76%)     4/50 (8.00%)  
amylase * 1    
# participants affected / at risk     5/51 (9.80%)     4/50 (8.00%)  
AST * 1    
# participants affected / at risk     4/51 (7.84%)     3/50 (6.00%)  
hypokalemia * 1    
# participants affected / at risk     3/51 (5.88%)     1/50 (2.00%)  
hypophosphatemia * 1    
# participants affected / at risk     3/51 (5.88%)     1/50 (2.00%)  
metabolic / lab - other * 1    
# participants affected / at risk     3/51 (5.88%)     1/50 (2.00%)  
hypomagnesemia * 1    
# participants affected / at risk     3/51 (5.88%)     0/50 (0.00%)  
Nervous system disorders      
neuropathy: sensory * 1    
# participants affected / at risk     8/51 (15.69%)     7/50 (14.00%)  
dizziness * 1    
# participants affected / at risk     6/51 (11.76%)     3/50 (6.00%)  
Respiratory, thoracic and mediastinal disorders      
voice changes * 1    
# participants affected / at risk     3/51 (5.88%)     1/50 (2.00%)  
Skin and subcutaneous tissue disorders      
rash / desquamation * 1    
# participants affected / at risk     19/51 (37.25%)     6/50 (12.00%)  
pruritus * 1    
# participants affected / at risk     12/51 (23.53%)     2/50 (4.00%)  
hand-foot skin reaction * 1    
# participants affected / at risk     11/51 (21.57%)     1/50 (2.00%)  
alopecia * 1    
# participants affected / at risk     9/51 (17.65%)     2/50 (4.00%)  
injection site reaction * 1    
# participants affected / at risk     6/51 (11.76%)     4/50 (8.00%)  
dermatology - other * 1    
# participants affected / at risk     6/51 (11.76%)     4/50 (8.00%)  
flushing * 1    
# participants affected / at risk     5/51 (9.80%)     3/50 (6.00%)  
dry skin * 1    
# participants affected / at risk     3/51 (5.88%)     2/50 (4.00%)  
acne * 1    
# participants affected / at risk     4/51 (7.84%)     0/50 (0.00%)  
* Events were collected by non-systematic assessment
1 Term from vocabulary, NCI-CTCAE v.3.0



  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.


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