A 3rd/4th Line Placebo-controlled Trial of Sorafenib in Patients With Predominantly Non Squamous Non-Small Cell Lung Cancer NSCLC. (MISSION)

Inclusion Criteria:

• Ability to understand and willingness to sign a written Informed Consent
• Advanced relapsed or refractory predominantly non squamous NSCLC. The diagnosis must have been confirmed cyto-/ histologically
• Patients must have measurable or non-measurable disease
• At least two but not more than three prior standard treatment regimens for NSCLC
• ECOG Performance Status of 0 or 1
• Male or female subjects >/= 18 years of age (>/=20 for Japan) at the time of Informed Consent
• Life expectancy of at least 12 weeks
• Ability to swallow oral medication
• Both men and women using adequate barrier birth control measures during the course of the trial and 4 weeks after the completion of trial

• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of the study drug:

  • Haemoglobin > 9.0 g/dl
  • Absolute neutrophil count (ANC) >1,500/mm3
  • Platelet count >/= 100,000/µl
  • Total bilirubin </=1.5 x the upper limit of normal
  • ALT < 2.5 x upper limit of normal (</= 5 x upper limit of normal in patients with liver metastases) AST < 2.5 x upper limit of normal (</= 5 x upper limit of normal in patients with liver metastases)
  • Alkaline phosphatase < 4 x upper limit of normal (</= 5 x upper limit of normal in patients with liver metastases)
  • PT-INR or PTT < 1.5 x upper limit of normal
  • Serum creatinine < 1.5 x upper limit of normal
  • Calculated creatinine clearance of >/= 50 mL/min

Exclusion Criteria:

• NSCLC patients with predominantly squamous cell carcinoma histology

Excluded medical conditions:

• History of cardiac disease: Congestive heart failure, Active coronary artery disease (CAD), Cardiac arrhythmias (>Grade 2 NCI-CTCAE vers. 3.0)
• Uncontrolled hypertension despite two anti-hypertensive medications
• History of HIV infection or chronic hepatitis B or C
• History of organ allograft
• Active clinically serious infections (> grade 2 NCI-CTCAE vers. 3.0)
• Patients with seizure disorder requiring medication
• Patients with evidence or history of bleeding diathesis or coagulopathy
• Patients undergoing renal dialysis
• Pulmonary hemorrhage/ bleeding event >/= CTCAE grade 2 within four weeks prior to the first dose of the study drug
• Any other hemorrhage/ bleeding event >/= CTCAE grade 3 within four weeks prior to the first dose of the study drug
• Thrombotic or embolic venous or arterial events such as cerebrovascular accident
• Pregnant or breast-feeding women.
• Any condition which could affect the absorption or pharmacokinetics of the study drug
• Prior treatment with other VEGF(R) inhibitors, including compounds that impact vascularity (i.e. sunitinib, thalidomide, vandetanib, vascular disrupting agents [VDA], VEGF-trap and other experimental agents of this class). Only bevacizumab (Avastin) is permitted.