A 3rd/4th Line Placebo-controlled Trial of Sorafenib in Patients With Predominantly Non Squamous Non-Small Cell Lung Cancer (NSCLC).
Condition: Carcinoma; Non-Small-Cell Lung
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Sorafenib (Nexavar, BAY43-9006); Placebo
Intervention description: Sorafenib 400 mg twice daily (BID); Placebo - 2 tablets twice daily (BID)
Intervention MeSH terms: Sorafenib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 703.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-Small Cell Lung Cancer (NSCLC); Sorafenib

Summary:

      The purpose of the study is to see if sorafenib plus best supportive care (i.e. in addition
      to the non-cancer treatments patients would normally receive) is an effective treatment for
      lung cancer compared to best supportive care alone. The safety and tolerability of the two
      treatment groups will also be compared. The goal of the study is to test the ability of
      sorafenib to improve survival compared to best supportive care alone.
    

Eligibility criteria:

        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

          -  Eastern Cooperative Oncology Group (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

               -  Alanine aminotransferase (ALT) < 2.5 x upper limit of normal (</= 5 x upper limit
                  of normal in patients with liver metastases) Aspartate aminotransferase (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)

               -  Prothrombin Time (PT)-International Normalized Ratio (INR) or Partial
                  Thromboplastin Time (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 [National Cancer Institute-Common
             Terminology Criteria for Adverse Events] vers. 3.0)

          -  Uncontrolled hypertension despite two anti-hypertensive medications

          -  History of Human immunodeficiency virus (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 Vascular Endothelial Growth Factor (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.