Intra-patient Dose Escalation Study of Sorafenib in Advanced Non-small Cell Lung Cancer

Inclusion Criteria:

Histologically or cytologically confirmed, advanced (stage IIIB with pleural effusion, stage IV, or recurrent), kras mutation positive, non-small cell lung cancer (NSCLC)
Measurable disease per RECIST criteria
Patients must have received one + prior chemotherapy regimens for NSCLC
Patients may have treated and clinically stable brain metastases
Adequate bone marrow, liver and renal function
Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to the start of treatment
Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation, and for 3 months after last administration of sorafenib
Patients must have the ability to understand and willingness to sign a written informed consent
International normalized ratio(INR) < 1.5 or prothrombin time/ partial thromboplastin time (PT/PTT) within normal limits

Exclusion Criteria:

Prior exposure to a Ras pathway inhibitor
Any other anti-tumor therapy within 3 weeks of enrollment
Prior bevacizumab within the past 6 weeks
An active secondary malignancy except non-melanoma skin cancer
Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have unstable angina or new onset angina or myocardial infarction within the past 6 months
Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
Uncontrolled hypertension, defined as systolic blood pressure > 150mm Hg or diastolic pressure > 90mm Hg, despite optical medical management
Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C
Active clinically serious infection > Common Terminology Criteria for Adverse Events (CTCAE) Grade 2
Thrombolic or embolic events such as cerebrovascular accident including transient ischemic attack within the past 6 months
Pulmonary hemorrhage/bleeding event >/= CTCAE Grade 2 within 4 weeks of first dose of study drug
Any other hemorrhage/bleeding event >/= CTCAE Grade 3 within 4 weeks of first dose of study drug
Serious non-healing wound, ulcer, or bone fracture
Evidence or history of bleeding diathesis or coagulopathy
Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug
Use of St. John's Wort or rifampin
Known or suspected allergy to sorafenib or any agent given in the course of the trial
Any condition that impairs patient's ability to swallow whole pills
Any malabsorption problem