Dose Escalating Study With BAY43-9006 With Carboplatin, Paclitaxel and Bevacizumab in Untreated Stage IIIb Non-small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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To determine the tolerability, maximum tolerated dose and pharmacokinetics of this drug.

Official Title
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Study of BAY43-9006 (Sorafenib) in Combination With Carboplatin, Paclitaxel and Bevacizumab in Previously Untreated Patients With Stage IIIB (With Malignant Pleural Effusions) or Stage IV Non-small Cell Lung Cancer (NSCLC)

Conditions
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Carcinoma, Non-Small-Cell Lung, Lung Cancer

Intervention / Treatment
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* Drug: Nexavar (Sorafenib, BAY43-9006)
* Drug: Nexavar (Sorafenib, BAY43-9006)
* Drug: Bevacizumab
* Drug: Bevacizumab
* Drug: Bevacizumab
* Drug: Bevacizumab
* Drug: Paclitaxel
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have Stage IIIB (with malignant pleural effusions) or Stage IV histological or cytological confirmation of non-small cell carcinoma (excluding squamous) Age >/= 18 years old Patients must have at least 1 evaluable lesion. Lesions must be evaluated by CT scan or MRI ECOG Performance Status of 0 to 1 Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of first dose: Hemoglobin >/= 9.0 g/dL White blood cell (WBC) count >/= 2,500/mm3 Absolute neutrophil count (ANC) >/= 1,500/mm3 Platelet count >/= 100,000/mm3 Total bilirubin </= 1.5 times the upper limit of normal (ULN) ALT and AST </= 2.5 X ULN (</= 5 X ULN for patients with liver involvement) INR </= 1.5 and aPTT within normal limits Serum creatinine </= ULN or creatinine clearance (CrCl) >/= 45 mL/min (CrCl = Wt (kg) x (140-age)/72 x Cr level, female x 0.85) for patients with creatinine levels above institutional normal Urinalysis (UA) must show less than 1+ protein in urine, or the patient will require a repeat UA. If repeat UA shows 1+ protein or more, a 24 hour urine collection will be required and must show total protein </= 1000 mg/24 hour to be eligible Exclusion Criteria: Patients with squamous histology Cardiac disease: Congestive heart failure > Class II NYHA; active coronary artery disease (MI more than 6 months prior to study entry is allowed); or serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management HIV infection or chronic hepatitis B or C Active clinically serious infections (> Grade 2 NCI-CTC Version 3.0) Evidence or history of CNS disease, including primary brain tumors, seizures disorders, or any brain metastasis

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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: Nexavar (Sorafenib, BAY43-9006)<br>* Sorafenib 200 mg orally BID interrupted dosing<br>Drug: Bevacizumab<br>* Bevacizumab 5 mg/kg intravenously<br>Drug: Paclitaxel<br>* Paclitaxel 200 mg/m² intravenously<br>Drug: Carboplatin<br>* Carboplatin AUC 6 intravenously<br>|
| Experimental: Arm 2<br> | Drug: Nexavar (Sorafenib, BAY43-9006)<br>* Sorafenib 200 mg orally BID interrupted dosing<br>Drug: Bevacizumab<br>* Bevacizumab 10 mg/kg intravenously<br>Drug: Paclitaxel<br>* Paclitaxel 200 mg/m² intravenously<br>Drug: Carboplatin<br>* Carboplatin AUC 6 intravenously<br>|
| Experimental: Arm 3<br> | Drug: Nexavar (Sorafenib, BAY43-9006)<br>* Sorafenib 400 mg orally BID interrupted dosing<br>Drug: Bevacizumab<br>* Bevacizumab 2.5 mg/kg intravenously<br>Drug: Paclitaxel<br>* Paclitaxel 200 mg/m² intravenously<br>Drug: Carboplatin<br>* Carboplatin AUC 6 intravenously<br>|
| Experimental: Arm 4<br> | Drug: Nexavar (Sorafenib, BAY43-9006)<br>* Sorafenib 400 mg orally BID interrupted dosing<br>Drug: Bevacizumab<br>* Bevacizumab 5 mg/kg intravenously<br>Drug: Paclitaxel<br>* Paclitaxel 200 mg/m² intravenously<br>Drug: Carboplatin<br>* Carboplatin AUC 6 intravenously<br>|
| Experimental: Arm 5<br> | Drug: Nexavar (Sorafenib, BAY43-9006)<br>* Sorafenib 400 mg orally BID interrupted dosing<br>Drug: Bevacizumab<br>* Bevacizumab 7.5 mg/kg intravenously<br>Drug: Paclitaxel<br>* Paclitaxel 200 mg/m² intravenously<br>Drug: Carboplatin<br>* Carboplatin AUC 6 intravenously<br>|
| Experimental: Arm 6<br> | Drug: Nexavar (Sorafenib, BAY43-9006)<br>* Sorafenib 400 mg orally BID interrupted dosing<br>Drug: Bevacizumab<br>* Bevacizumab 10 mg/kg intravenously<br>Drug: Paclitaxel<br>* Paclitaxel 200 mg/m² intravenously<br>Drug: Carboplatin<br>* Carboplatin AUC 6 intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary objective of this study is to define the safety profile and maximum tolerated dose (MTD) of BAY43-9006 (sorafenib) administered in combination with, carboplatin, paclitaxel and bevacizumab |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary objectives include evaluation of pharmacokinetics, biomarkers, pharmacodynamics and tumor response of patients treated with BAY43-9006 (sorafenib) in combination with bevacizumab, paclitaxel and carboplatin |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung, cancer, NSCLC