Preoperative Folfirinox, Radiation Therapy for Resectable Adenocarcinoma of the Pancreas

Study Drug Administration: You will receive up to 3 phases of study therapy: the systemic chemotherapy phase, the chemoradiation phase, and surgery, if possible. During the systemic chemotherapy phase, you will receive mFolfirinox 1 time every 2 weeks (Weeks 1, 3, 5, 7, 9 and 11) for 12 weeks. You will receive oxaliplatin by vein over a 2-hour period. After receiving oxaliplatin, you will receive irinotecan by vein over a 90-minute period. After receiving irinotecan, you will then receive 5-FU through a portable pump for the next 46 hours. You will take the portable pump home with you and will receive instructions on how to use it. You will begin receiving chemoradiation within 6 weeks after you have finished receiving the Week 11 dose of mFolfirinox. However, you will not begin receiving it until you have recovered from side effects of the chemotherapy. During the chemoradiation phase, you will receive gemcitabine over about 35 minutes 1 time each week for 5 weeks. You will also receive radiation therapy 5 days a week (Monday through Friday) for 5 1/2 weeks (a total of 28 treatments). If you miss any of the days of radiation, they will be made up at the end of treatment so that you will receive the full amount of radiation. You will be given a separate consent form that explains the radiation procedure and the risks it may present. After the chemoradiation phase, you will not receive any treatment for 4-6 weeks so your body can recover. If after this time the disease has not gotten worse or spread to other parts of the body, you will have surgery to try to remove the tumor. You will be given a separate consent form for the surgery that describes how it is performed and its risks. If the disease has gotten worse or spread to other parts of the body, you will not be able to have surgery. The study doctor will discuss other therapy options with you. Study Visits: At Weeks 1, 3, 5, 7, 9, and 11 of the systemic chemotherapy phase: * You will have a physical exam, including measurement of your weight and vital signs (blood pressure and heart rate). * Blood (about 3 tablespoons) will be drawn for routine tests. Within 4 weeks before beginning the chemoradiation phase: * You will have CT or MRI scans to check the status of the disease. * Blood (about 1 tablespoon) will be drawn for tumor marker testing. At Weeks 1, 2, 3, 4, 5, and 6 of the chemoradiation phase: * You will have a physical exam, including measurement of your weight and vital signs. * Blood (about 2-3 tablespoons) will be collected for routine tests. At Week 6, an additional 2 teaspoons of blood will be drawn for CTC testing. About 4 to 6 weeks after you complete the chemoradiation phase: * Blood (about 1 tablespoon) will be drawn for tumor marker testing. * You will have CT or MRI scans to check the status of the disease. If you are eligible to have surgery after the chemoradiation phase, the following tests and procedures will also be performed: * Blood (about 4 teaspoons total) will be drawn within 2 weeks before surgery for CTC testing. Blood will also be collected during surgery, if the surgeon thinks it is safe and feasible. * Tumor tissue collected during a previous procedure will be used for biomarker testing. An additional sample of tumor tissue will be collected from the tissue removed during surgery and used for biomarker testing. Biomarkers are found in the blood/tissue and may be related to your reaction to the study drug. Length of Study: You will receive study treatment over the course of up to 30 weeks. You will be taken off study if the disease gets worse, the study doctor thinks it is in your best interest, or if you do not follow the study directions. You may choose to stop receiving the study treatment at any time. If you choose to stop, you should tell the study doctor or a member of the staff right away. They will make sure that proper procedures are followed and a final visit will be scheduled for your safety. Follow-up: Blood (about 2 teaspoons) will be collected for CTC testing 2-3 months after your surgery, if you were one of the first 30 participants enrolled in the study. You will have a CT or MRI scan of the abdomen and pelvis every 4 months for 2 years to check the status of the disease. This is an investigational study. 5-FU, oxaliplatin, irinotecan, and gemcitabine are each FDA approved and commercially available to treat different types of cancer: * 5-FU: pancreatic, gastric, breast, colon/rectum, and skin cancer (basal cell carcinoma) * Oxaliplatin: colon and rectal cancer * Irinotecan: colorectal cancer * Gemcitabine: pancreatic, lung, ovarian, and breast cancer. The use of these 4 drugs together and in combination with radiation therapy for the treatment of pancreatic cancer is investigational. Up to 33 patients will be enrolled in this study. All will be enrolled at MD Anderson.