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)

Study Overview
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Brief Summary
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A randomized controlled trial comparing safety and efficacy of carboplatin and paclitaxel plus or minus sorafenib in chemonaive patients with stage III-IV non-small cell lung cancer.

Official Title
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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)

Conditions
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Carcinoma, Non-Small Cell Lung

Intervention / Treatment
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* Drug: Nexavar (Sorafenib, BAY43-9006) + carboplatin + paclitaxel
* Drug: Carboplatin plus Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage IIIB (with effusion) or Stage IV NSCLC any histology No prior chemotherapy Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Greater than or equal to 18 years of age Life expectancy at least 12 weeks Adequate bone marrow, liver and renal function Exclusion Criteria: Prior systemic anti cancer therapy Known brain metastasis. Patients with neurological symptoms should undergo at computed tomography (CT) scan/magnetic resonance imaging (MRI) of the brain to exclude brain metastasis Pulmonary hemorrhage/bleeding event > Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 within 4 weeks of first dose of study drug Thrombotic or embolic events including Transient ischemic attack (TIA) within the past 6 months Uncontrolled hypertension Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug Major surgery within 4 weeks Evidence or history of bleeding diathesis or coagulopathy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sorafenib + C/P<br>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. | Drug: Nexavar (Sorafenib, BAY43-9006) + carboplatin + paclitaxel<br>* 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.<br>|
| Active Comparator: Placebo + C/P<br>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. | Drug: Carboplatin plus Paclitaxel<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) in Patients Treated With Carboplatin, Paclitaxel and Sorafenib to OS in Patients Treated With Carboplatin, Paclitaxel and Placebo | Overall survival determined as the time (days) from the date of randomization at start of study to the date of death, due to any cause. Outcome measure was assessed regularly, i.e. every 3 weeks during study treatment and every 3 months during post-treatment. | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS determined as time (days) from the date of randomization at start of study to disease progression (radiological or clinical) or death due to any cause, if death occurs before progression. | 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 | 
| Overall Best Response | Best overall tumor response for the ITT population was determined according to Response Evaluation Criteria in Solid Tumors (RECIST). Categories: complete response (CR, tumor disappears), partial response (PR, sum of lesion sizes decreased), stable disease (SD, steady state of disease), progressive disease (PD, sum of lesion sizes increased). | 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 | 
| Duration of Response | Duration of response (PR or better) is defined as the time from the first documented objective response of PR or CR, whichever is noted earlier, to disease progression or death (if death occurs before progression is documented). | 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 | 
| 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) | Functional Assessment of Cancer Therapy - Lung cancer subscore (FACT-L). Patient reported outcome as assessed by FACT-L score. FACT-L questionnaire comprises statements about physical, social / family, emotional and functional well-being as well as additional concerns which have to be rated by the patients (0=not at all to 4=very much). Cycle duration defined as 21 days. Change from baseline in Total FACT-L on day 1 of cycles 3,5,7,9 (weeks 7,13,19 and 25) and end of treatment (EOT); cycle 1, day 1 used as baseline. EOT is determined by patient's last visit after treatment discontinuation. | 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 | 
| 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) | Lung Cancer Symptoms (LCS) subscale ranges from 0 (severe debilitation) to 28 (asymptomatic). Cycle duration defined as 21 days. Change from baseline in LCS Subscale on day 1 of cycles 2 through 9 (weeks 4,7,10,13,16,19,22 and 25) and end of treatment (EOT); cycle 1, day 1 used as baseline. EOT is determined by patient's last visit after treatment discontinuation. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Small Cell Lung Cancer, NSCLC