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

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)

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

Study Overview

• Status: Completed
• Conditions: Carcinoma, Non-Small-Cell Lung; Lung Cancer
• Intervention / Treatment: Drug: Nexavar (Sorafenib, BAY43-9006); Drug: Nexavar (Sorafenib, BAY43-9006); Drug: Bevacizumab; Drug: Bevacizumab; Drug: Bevacizumab; Drug: Bevacizumab; Drug: Paclitaxel; Drug: Carboplatin

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
  • Texas
    • Houston, Texas, United States, 77030

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: February 15, 2010
• First Submitted That Met QC Criteria: February 16, 2010
• First Posted (Estimate): February 17, 2010

Study Record Updates

• Last Update Posted (Estimate): November 13, 2013
• Last Update Submitted That Met QC Criteria: November 12, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: NSCLC; cancer; Lung
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Carboplatin; Paclitaxel; Sorafenib; Bevacizumab
• Other Study ID Numbers: 11956