A Randomized, Phase III Study Comparing Carboplatin/Paclitaxel or Carboplatin/Paclitaxel/Bevacizumab with or without Concurrent Cetuximab in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC)

Histologically or cytologically proven primary NSCLC (adenocarcinoma, large cell carcinoma, squamous cell carcinoma or unspecified). Disease must be Stage IV. Disease may be either newly diagnosed or recurrent after previous surgery and/or irradiation. Must have measurable or non-measurable disease (see Section 10.1) documented by CT or MRI. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Measurable disease must be assessed within 28 days prior to registration. Non-measurable disease must be assessed within 42 days prior to registration. Must not have brain mets unless: (1) mets have been treated and have remained controlled for at least two weeks following treatment, and (2) patient has no residual neurological dysfuntion off corticosteroids for at least 1 day. Must have a CT or MRI scan of the brain within 42 days prior to registration. Zubrod Performance Status of 0-1. May have received prior radiation therapy provided that patient has recovered from all associated toxicities at the time of registration. May have received prior surgery. Timeframe of surgery depends on whether it is planned for the patient to receive bevacizumab (see Section 5.1g). Must be no anticipation of need for major surgical procedures during protocol treatment. Must not have received prior chemotherapy for any stage non-small cell lung cancer, prior platinum-based chemotherapy for any purpose, cetuximab, gefitinib, erlotinib or other investigational agents that target the EGFR pathway; any prior VEGF-related agents or have received prior chimerized or murine monoclonal antibody (or have documented presence of HAMA). Must have an ANC >/= 1,500/mcl, platelet count of >/= 100,000/mcl and hemoblobin >/=9 g/dL obtained within 14 days prior to registration. Must have within 14 days prior to registration: serum bilirubin </= 2 x IULN, either SGOT or SGPT </= 2 x IULN, serum creatinine </= IULN AND a measured or calculated creatinine clearance >/= 50 mL/min. If patient is planned to receive bevacizumab, UPC ratio obtained within 14 days prior to registration - if UPC ratio > 0.5, 24 hour urine protein must be < 1000 mg. Must be offered participation in the additional integral translational medicine studies as outlined in Section 5.1d. Must not have >/= Grade 2 neuropathy-sensory. Must not have documented evidence of acute hepatitis or an active uncontrolled infection. Must not have history (within past 6 months) of CVA, unstable angina, myocardial infarction; or at the time of registration uncontrolled hypertension, NYHA Class 2 or greater CHF; serious cardiac arrhythmia requiring medication, or clinically significant peripheral vascular disease. Must have no know hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies. Must be willing to provide prior smoking history. No prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years. Must not be pregnant or nursing because of the increased risk of fetal harm including fetal death from the chemotherapeutic agents.