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A Randomized Controlled Trial Comparing Safety and Efficacy of Carboplatin and Paclitaxel Plus or Minus Sorafenib (BAY 43-9006) in Chemonaive Patients With Stage IIIB-IV Non-Small Cell Lung Cancer (NSCLC)

This study has been terminated.
(Based on the results of the interim analysis, it was determined that the study would not meet its primary efficacy endpoint and the study was terminated early.)
Sponsor:
Information provided by:
Bayer
ClinicalTrials.gov Identifier:
NCT00300885
First received: March 8, 2006
Last updated: December 3, 2012
Last verified: December 2012
History of Changes
Results First Received: November 4, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double-Blind;   Primary Purpose: Treatment
Condition: Carcinoma, Non-Small Cell Lung
Interventions: Drug: Nexavar (Sorafenib, BAY43-9006) + carboplatin + paclitaxel
Drug: Carboplatin plus Paclitaxel

  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
This study was conducted at 150 centers across 20 countries, which enrolled and randomized at least one subject. From a total of 1043 subjects who were screened, 926 subjects were randomized between 15 February 2006 and 9 May 2007 in 20 countries.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of the 926 subjects who were randomized, 922 received at least one dose of study drug. All 926 subjects were included in the ITT population (intent-to-treat; defined as all randomized patients), all but four subjects did receive study drug. They were not included in the safety population.

Reporting Groups
  Description
Sorafenib + C/P Chemotherapy Phase up to 6 cycles: Sorafenib (Nexavar, BAY43-9006), [400 mg orally, twice daily] on Study Days 2-19 and paclitaxel (P) (200 mg/m2, intravenous (IV)) and carboplatin (C) (area under the curve (AUC) =6 mg/ml*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib 400 mg orally twice daily was administered on Days 1-21 of each 21-day cycle.
Placebo + C/P Chemotherapy Phase up to 6 cycles: Sorafenib Placebo (2 tablets orally twice daily] on Study Days 2-19 and paclitaxel (200 mg/m2, intravenous (IV)) and carboplatin (area under the curve (AUC) =6 mg/ml*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib Placebo 2 tablets orally twice daily was administered on Days 1-21 of each 21-day cycle.

Participant Flow for 2 periods

 Period 1:   Treatment
    Sorafenib + C/P     Placebo + C/P  
STARTED     464     462 [1]
Received Treatment     463     459  
COMPLETED     91     88  
NOT COMPLETED     373     374  
Adverse Event                 134                 82  
Death                 20                 7  
Lack of Efficacy                 1                 1  
Lost to Follow-up                 3                 2  
Physician Decision                 4                 5  
Protocol Violation                 11                 11  
Withdrawal by Subject                 26                 23  
Disease progression                 171                 238  
Random code broken (subject died)                 0                 1  
Non-compliant with study medication                 3                 4  
[1] ongoing in double -blind treatment at data cut-off

Period 2:   Follow-up
    Sorafenib + C/P     Placebo + C/P  
STARTED     354 [1]   369 [1]
COMPLETED     176 [2]   174 [2]
NOT COMPLETED     178     195  
Death                 141                 163  
Lost to Follow-up                 11                 7  
Withdrawal by Subject                 26                 25  
[1] Subjects entered Follow-up period after termination of Treatment period due to any reason.
[2] Subjects still in Follow up period at data cut-off date.



  Baseline Characteristics
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Reporting Groups
  Description
Sorafenib + C/P Chemotherapy Phase up to 6 cycles: Sorafenib (Nexavar, BAY43-9006), [400 mg orally, twice daily] on Study Days 2-19 and paclitaxel (P) (200 mg/m2, intravenous (IV)) and carboplatin (C) (area under the curve (AUC) =6 mg/ml*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib 400 mg orally twice daily was administered on Days 1-21 of each 21-day cycle.
Placebo + C/P Chemotherapy Phase up to 6 cycles: Sorafenib Placebo (2 tablets orally twice daily] on Study Days 2-19 and paclitaxel (200 mg/m2, intravenous (IV)) and carboplatin (area under the curve (AUC) =6 mg/ml*min-1, IV) on Study Day 1. The cycle duration 21 days. Maintenance Phase: Sorafenib Placebo 2 tablets orally twice daily was administered on Days 1-21 of each 21-day cycle.
Total Total of all reporting groups

Baseline Measures
    Sorafenib + C/P     Placebo + C/P     Total  
Number of Participants  
[units: participants]
 		  464     462     926  
Age  
[units: years]
Median ( Full Range ) 		  62  
  ( 34 to 86 )   		  63  
  ( 34 to 82 )   		  62  
  ( 34 to 86 )  
Gender  
[units: participants]
 		     
Female     171     174     345  
Male     293     288     581  
ECOG (Eastern Cooperative Oncology Group) Performance Status [1]
[units: Participants]
 		     
0     190     188     378  
1     274     274     548  
Geographic region [2]
[units: Participants]
 		     
core     325     323     648  
non-core     139     139     278  
NSCLC Classification [3]
[units: Participants]
 		     
Adenocarcinoma NSCLC     263     271     534  
Bronchoalveolar     6     5     11  
Non-Microcellulare carcinoma     0     1     1  
Large cell carcinoma     23     30     53  
Squamous cell carcinoma     109     114     223  
Non-Small cell lung cancer carcinoma     10     10     20  
Undifferentiated carcinoma     46     26     72  
Poorly differentiated non-small cell carcinoma     4     3     7  
Neuro-Endocrine carcinoma     0     1     1  
Low differentiated carcinoma (neuro-endocrine)     1     0     1  
Unknown or unspecified histology     2     1     3  
Stage at Study Entry [4]
[units: Participants]
 		     
Stage III B     44     47     91  
Stage IV     420     415     835  
[1] ECOG 0 versus 1 was a stratification factor for randomization. ECOG Performance Status is a rating of daily living abilities, from 0 to 5: 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.
[2] Geographic region (core versus non-core) was stratification factor for randomization. Core region comprises North America, Northern/Western Europe, and Australia. Non-core region comprises South America, Eastern Europe, and Asia-Pacific.
[3] Histology (squamous versus non-squamous) was a stratification factor for randomization.
[4] Stage IIIB (according to American Joint Committee on Cancer): primary tumor any stage, regional lymph node stage N3, no distant metastasis OR primary tumor stage T4, regional lymph node any stage, no distant metastasis. Stage IV: primary tumor any stage, regional lymph node any stage, distant metastasis present.



  Outcome Measures
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1.  Primary:   Overall Survival (OS) in Patients Treated With Carboplatin, Paclitaxel and Sorafenib to OS in Patients Treated With Carboplatin, Paclitaxel and Placebo   [ Time Frame: Outcome measure was assessed every 3 weeks starting from randomization, during treatment period and every 3 months during follow-up period until death was recorded or up to data cutoff (1Oct2007) used for planned formal interim analysis ]
  Show Outcome Measure 1

2.  Secondary:   Progression Free Survival (PFS)   [ Time Frame: Tumor measurements and assessments based on RECIST criteria were performed every 6 weeks for the first 18 weeks of therapy ( week 6, 12, and 18) and every 12 weeks thereafter up to data cutoff (1Oct2007) used for planned formal interim analysis ]
  Show Outcome Measure 2

3.  Secondary:   Overall Best Response   [ Time Frame: Tumor measurements and assessments based on RECIST criteria were performed every 6 weeks for the first 18 weeks of therapy ( week 6, 12, and 18) and every 12 weeks thereafter up to data cutoff (1Oct2007) used for planned formal interim analysis ]
  Show Outcome Measure 3

4.  Secondary:   Duration of Response   [ Time Frame: Tumor measurements and assessments based on RECIST criteria were performed every 6 weeks for the first 18 weeks of therapy ( week 6, 12, and 18) and every 12 weeks thereafter up to data cutoff (1Oct2007) used for planned formal interim analysis ]
  Show Outcome Measure 4

5.  Secondary:   Patient Reported Outcome as Assessed by FACT-L Score. Change From Baseline in Total FACT-L at Cycles 3,5,7,9 and End of Treatment (EOT)   [ Time Frame: Outcome measure was assessed on Day 1 of Cycle 1 and Day 1 of every other cycle (i.e. Cycle 3, 5, 7 etc.) during treatment and at end of treatment visit or up to data cutoff (10ct2007) used for planned formal interim analysis ]
  Show Outcome Measure 5

6.  Secondary:   Patient Reported Outcome as Assessed by LCS Subscale Score. Change From Baseline in LCS Subscale at Cycles 2 Through 9 and at End of Treatment (EOT)   [ Time Frame: Outcome measure was assessed on Day 1 of Cycle 1 and Day 1 of every cycle (i.e. Cycle 2, 3, 4, 5 etc.) during treatment and at end of treatment visit or up to data cutoff (10ct2007) used for planned formal interim analysis ]
  Show Outcome Measure 6


  Serious Adverse Events
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  Other Adverse Events
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  More Information
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