Phase II Study of Sorafenib + Carboplatin and Docetaxel in First Line Treatment of Stage IIIB/IV NSCLC

Study Overview
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Brief Summary
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This is an open-label, single institution, phase II study of Sorafenib in combination with docetaxel and carboplatin in patients with advanced non-small cell lung cancer. Docetaxel and carboplatin will be given on day 1 of every three week cycle. Patients will take Sorafenib twice a day on the 1st day of treatment and continue to take the medication every day until progression of disease, prohibitive toxicity, or patient withdrawal from the study. Chemotherapy courses will repeat every 21 days in the absence of disease progression or unacceptable toxicity for a total of four cycles.

Detailed Description
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Patients will be monitored after every two cycles (6 weeks) for tumor response, stability, or progression by radiographic imaging studies. The primary goal of this study is to determine the clinical response rate of this regimen in patients with advanced lung cancer. Secondary endpoints include time to progression, overall survival, and toxicity. Blood levels of ERK-phosphorylation, activated caspase 3, cyclin D1, anti -cIAP2, p-Akt, and Mcl1 activity will be measured at the beginning, middle and end of therapy to help identify predictors of drug response and toxicity during the first cycle of treatment.

Official Title
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A Phase II Study of Sorafenib in Combination With Carboplatin and Docetaxel in the First Line Treatment of Stage IIIB/IV Non-Small Cell Lung Cancer

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Sorafenib + Docetaxel/Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed NSCLC with clinical or radiological evidence of advanced disease (Stage IIIB/IV) Uni-dimensionally measurable disease Age => 18 years ECOG performance status of 0-1 Life expectancy > 3 months Exclusion Criteria: Small-cell or mixed histologies including a small cell component Prior chemotherapy, biotherapy, radiotherapy to an area of measurable disease Patients with peripheral neuropathy grade => 2

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sorafenib + Docetaxel/Carboplatin<br>400 mg po BID Sorafenib + 75 mg/m2 IV Docetaxel on day 1 plus AUC 6 on Carboplatin on day 1 of each 21 day cycle | Drug: Sorafenib + Docetaxel/Carboplatin<br>* 400 mg po BID Sorafenib + 75 mg/m2 IV Docetaxel on day 1 plus AUC 6 on Carboplatin on day 1 of each 21 day cycle<br>* Other names: Carboplatin: Paraplatin, CBDCA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Patients With Stage IIIB/IV NSCLC Response Rate to the Combination Therapy of Sorafenib and Docetaxel/Carboplatin | The response rate from the combination therapy of Sorafenib and Docetaxel/carboplatin for patients with Stage IIIB/IV NSCLC.The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria (see section 9.3.1).Tumor Response: Evaluation of target lesions Complete Response (CR): Disappearance of all target lesions Partial Response (PR): a) At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): a) At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants the Progression-free Survival (PFS) . | Disease progression is based on RECIST documentation. Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions | 30 months | 
| Number of Participants With Serious Adverse Events | Assessment of adverse events related to the combination infusion, These include a Serious Adverse Event (SAE) is an adverse event occurring at any dose that results in any of the following outcomes: Death Life-threatening Persistent or significant disability/incapacity In patient hospitalization or prolongation of existing hospitalization Congenital anomaly/birth defect or • blood dyscrasia without inpatient hospitalization convulsions without inpatient hospitalization intensive treatment in an emergency room or at home for allergic bronchospasm without inpatient hospitalization development of drug dependency drug abuse overdose with an associated serious event, or required intervention to prevent impairment/damage | 30 months | 
| The Number of Participants With Biomarkers of Sorafenib Activity and Toxicity | Monitored at designated timepoints.All patients will be evaluable for toxicity from the time of their first treatment with SORAFENIB. | 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stage IIIB/IV