BATTLE-FL: Front-Line Biomarker-Integrated Treatment Study in Non Small Cell Lung Cancer

The Study Drugs: Carboplatin is designed to interfere with the growth of cancer cells by stopping cell division, which may cause the cells to die. Pemetrexed is designed to block enzymes in the body that play a part in tumor growth. Bevacizumab is designed to block the growth of blood vessels that supply nutrients necessary for tumor growth. This may prevent or slow down the growth of cancer cells. Cixutumumab is a monoclonal antibody, which means that it attaches to specific targets on cancer cells. These targets are called IGF-1R and help the cancer cells grow and divide. Cixutumumab is designed to block these receptors on tumor cells that may cause tumors to grow. Study Groups and Drug Administration (Combination Therapy): If you are found to be eligible to take part in this study, you will be randomly assigned (as in the roll of dice) to 1 of 3 groups. You will have an equal chance of being assigned to each group. Each cycle is 21 days (+/- 5 days). * If you are in Group 1, you will receive carboplatin and pemetrexed on Day 1 of each cycle. Carboplatin will be given by vein over 10 minutes. Pemetrexed will be given by vein over 30 minutes. * If you are in Group 2, you will receive bevacizumab, carboplatin, and pemetrexed on Day 1 of each cycle. Bevacizumab will be given by vein over about 90 minutes for the first dose, about 60 minutes for the second dose, and about 30 minutes for all other doses. Carboplatin will be given by vein over 10 minutes. Pemetrexed will be given by vein over 30 minutes. * If you are in Group 3, you will receive cixutumumab, carboplatin, and pemetrexed on Day 1 of each cycle. Cixutumumab is given by vein over 60 minutes. Carboplatin will be given by vein over 10 minutes. Pemetrexed will be given by vein over 30 minutes. Study Visits During Combination Therapy: If you are in Group 3, before you begin receiving study drugs, you will have a hearing test. On Day 1 (+/- 5 days) of Cycles 1, 2, and 4: * You will have a physical exam, including measurement of your weight and vital signs. * You will be asked about any drugs you may be taking and any side effects you may be having. * Your performance status will be recorded. * Blood (about 3 teaspoons) will be drawn for routine tests. * If you are in Group 2, urine will be collected for routine tests. On Days 8 and 15 of Cycle 1: °If you are in Group 3, blood (about 1 teaspoon) will be drawn for routine tests. On Day 1 of Cycle 3: * You will have a physical exam, including measurement of your weight and vital signs. * You will be asked about any drugs you may be taking and any side effects you may be having. * Your performance status will be recorded. * Blood (about 3 teaspoons) will be drawn for routine tests. * You will have a CT scan and/or MRI scan of the chest (and abdomen if the doctor thinks it is needed) to check the status of the disease. * You will have an MRI scan of the brain. * You will have a chest x-ray to check the status of the disease. * If you are in Group 2, urine will be collected for routine tests. At any time your doctor thinks it may be needed, blood (about 1 teaspoon) will be drawn to check how well your blood clots. Maintenance Therapy: After you have completed 4 cycles of combination therapy, you may be eligible for maintenance therapy. If you are in Group 1,you will receive pemetrexed by vein over 10 minutes on Day 1 (± 5 days) of every 21-day cycle. If you are in Group 2, you will receive pemetrexed by vein over 10 minutes and bevacizumab over about 30 minutes on Day 1 (± 5 days) of every 21-day cycle. If you are in Group 3, you will receive pemetrexed by vein over about 10 minutes and cixutumumab by vein over about 60 minutes on Day 1 (± 5 days) of every 21-day cycle. Study Visits During Maintenance Therapy: On Day 1 of each cycle: * You will have a physical exam, including measurement of your weight and vital signs. * You will be asked about any drugs you may be taking and any side effects you may be having. * Your performance status will be recorded. * Blood (about 3 teaspoons) will be drawn for routine tests. * You will have a CT scan and/or MRI scan of the chest (and abdomen if the doctor thinks it is needed) to check the status of the disease. * You will have an MRI scan of the brain. * You will have a chest x-ray to check the status of the disease. * If you are in Group 2, urine will be collected for routine tests. Length of Study: You may continue taking the study drug(s) for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse or intolerable side effects occur. Your participation on the study will be over once you have completed the end-of-dosing visit and follow-up. End-of-Dosing Visit: When you go off study for any reason, you will have an end-of-dosing visit. The following tests and procedures will be performed: * Your medical history will be recorded. * You will have a complete physical exam, including measurement of your weight and vital signs. * You will be asked about any drugs you may be taking and any side effects you may be having. * Your performance status will be recorded. * Blood (about 3 teaspoons) and urine will be collected for routine tests. * You will have a CT scan and/or MRI of the chest (and abdomen if the doctor thinks it is needed) to check the status of the disease. * You will have an MRI scan of the brain. * You will have a chest x-ray. * You will have an ECG. * If you are in Group 3, you will have a hearing test. Follow-Up: You will have follow-up every 4 weeks after you are no longer taking the study drugs. You will be contacted at a clinic visit or by phone. You will be called every 3 months for up to 3 years and asked about any cancer treatments you may be receiving. This phone call should take about 10 minutes. This is an investigational study. Carboplatin and pemetrexed are FDA approved and commercially available for the treatment of certain types of NSCLC. Bevacizumab is FDA approved and commercially available for treatment of certain types of colon or rectal cancer, NSCLC, and renal cell carcinoma. Cixutumumab is not FDA approved or commercially available. At this time, cixutumumab is only being used in research. Up to 225 patients will take part in this study. All will be enrolled at MD Anderson.