Sorafenib and Thoracic Radiation for Patients With Non-Small Cell Lung Cancer

• 1. Pathologically proven previously untreated or systemically treated poor prognosis NSCLC patients for whom palliative thoracic irradiation is the treatment of choice per standard of care. 2. Patients for whom palliative thoracic irradiation therapy to 45 Gy/15 FX is the recommended treatment by their treating radiation oncologist. 3. The primary tumor and/or regional lymphatic metastases must be evaluable radiographically. 4. Age \>/= 18 years or older. 5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 or greater, weight loss \</= 30% or less. 6. No prior radiation to the thorax. 7. Adequate bone marrow, liver and renal function as assessed by the following: \
• Hemoglobin \>/= 9.0 g/dl \
• Absolute neutrophil count (ANC) \>/=1,000/mm\^3 \*Platelet count \>/ =100,000/mm\^3 \
• Total bilirubin \</= 1.5 times ULN or greater \
• ALT and AST \</= 2.5 times the ULN (\</= 5 \
• ULN for patients with liver involvement) \
• Creatinine \</= 1.5 \
• ULN 8. Patients with distant metastasis are eligible. 9. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment 10. 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. Men should use adequate birth control for at least three months after the last administration of sorafenib. 11. Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures. 12. INR \< 1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable. 13. Patients must sign an informed consent indicating that they are aware of the investigational nature of the study in keeping with the policy of M.D. Anderson Cancer Center. The only approved consent form is attached to this protocol.

1. Cardiac disease: Congestive heart failure \> class II NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months. 2. Known hemorrhagic brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude hemorrhagic brain metastasis. 3. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy. 4. Uncontrolled hypertension defined as systolic blood pressure \> 140 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management. 5. Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C. 6. Active clinically serious infection \> CTCAE Grade 3. 7. Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months. 8. Pulmonary hemorrhage/bleeding event \> CTCAE Grade 2 within 4 weeks of first dose of study drug. 9. Any other hemorrhage/bleeding event \> CTCAE Grade 3 within 4 weeks of first dose of study drug. 10. Serious non-healing wound, ulcer, or bone fracture. 11. Evidence or history of bleeding diathesis or coagulopathy 12. Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug. 13. Current use of St. John's Wort or rifampin (rifampicin). 14. Known or suspected allergy to sorafenib. 15. Any malabsorption problem. 16. Patients with squamous cell carcinoma.