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

Sponsor

Bayer (Industry)

Overall Status

Completed

CT.gov ID

NCT01069328

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

16.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To determine the tolerability, maximum tolerated dose and pharmacokinetics of this drug.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung Lung Cancer	Drug: Nexavar (Sorafenib, BAY43-9006) Drug: Nexavar (Sorafenib, BAY43-9006) Drug: Bevacizumab Drug: Bevacizumab Drug: Bevacizumab Drug: Bevacizumab Drug: Paclitaxel Drug: Carboplatin	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

33 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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)

Study Start Date :

Jul 1, 2006

Actual Primary Completion Date :

Sep 1, 2011

Actual Study Completion Date :

Oct 1, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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