Biomarker-Integrated Approach of Targeted Therapy for Lung Cancer Elimination Plus External Beam Radiation Therapy (BATTLE-XRT)

Study Groups: If you are found to be eligible to take part in this study and you have an EGFR mutation, you will be enrolled in Arm A. If you have the wild-type EGFR, you will be randomly assigned (as in the flip of a coin) to either Arm B or C. You will have an equal chance of being enrolled in either arm. * If you are in Arm A, you will receive standard chemoradiation, erlotinib, and onartuzumab. * If you are in Arm B, you will receive standard chemoradiation, erlotinib, and onartuzumab. * If you are in Arm C, you will receive standard chemoradiation and onartuzumab only. If you are assigned to Arm A or B, you will receive standard chemoradiation, erlotinib, and onartuzumab. You will be assigned to a dose level of onartuzumab based on when you join this study. After the first dose level of onartuzumab is given, you will be watched for 2 weeks after the end of radiation treatment to check for any serious side effects at that dose level. If any participants in this first group have intolerable side effects, a lower dose combination of the study drugs may be tested. Once the highest tolerable dose is found, extra participants will receive onartuzumab at that dose level. All participants in Arms A and B will receive the same dose level of erlotinib. Study Drug Administration: All participants will receive onartuzumab by vein on Day 1 of each 3-week cycle. The first infusion should be given over about 60 minutes. If the infusion is tolerated, other doses will be given over about 30 minutes. You will receive paclitaxel and carboplatin by vein over about 6 hours 1 time a week for 7 weeks. You will receive a separate consent form for chemoradiation, which will describe the procedure and risks in more detail. If you are taking erlotinib, it should be taken by mouth with about 1 cup of water. You should take erlotinib at about the same time every day, at least 1 hour before a meal and at least 2 hours after a meal. Study Visits: One (1) time each week: * You will have a physical exam. * Blood (about 2 teaspoons) will be drawn for routine tests. If you are taking Coumadin or a similar drug, this blood will also be used to check how well your blood clots. Length of Study: You may continue taking onartuzumab until you complete radiation therapy. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Your participation on the study will be over 4 years after your last dose of study drug. Follow-Up: You will have follow-up visits around 30 days after your last dose of study drug, every 3 months for 2 years, and then every 4 months for the next 2 years. During these visits: * You will have a physical exam. * You will have a CT or PET scan to check the status of the disease. * If you are taking Coumadin or a similar drug, blood (about 2 teaspoons) will be drawn to check how well your blood clots. You will be called about every 4 weeks and asked how you are doing for as long as your doctor thinks it is needed. This is an investigational study. Onartuzumab is not FDA approved or commercially available. It is currently being used for research purposes only. Erlotinib, carboplatin, and paclitaxel are all FDA approved and commercially available for the treatment of NSCLC, but their use in this study is investigational. Radiation therapy is delivered using FDA-approved and commercially available methods. The study doctor can explain how the study drugs are designed to work. Up to 90 participants will take part in this study. All will be enrolled at MD Anderson.