Preoperative Chemotherapy (Gemcitabine and Erlotinib) With or Without Radiation Therapy

The Study Drugs: Gemcitabine is designed to disrupt the growth of cancer cells, which may cause cancer cells to die. Erlotinib is designed to block the activity of a protein found on the surface of many tumor cells that may control tumor growth and survival. This may stop tumors from growing. Screening Tests: Signing this consent form does not mean that you will be able to take part in this study. You will have "screening tests" to help the doctor decide if you are eligible to take part in this study. The following tests and procedures will be performed: * You will have a complete physical exam. * Blood (about 2 tablespoons) will be drawn for routine tests. This routine blood draw will include a pregnancy test for women who are able to have children. To take part in this study, the pregnancy test must be negative. * You will be asked about any side effects you may have experienced. * Urine will be collected for routine tests. * You will have chest x-rays and computed tomography (CT) scans of the abdomen to check the status of the disease. The study doctor will discuss the screening test results with you. If the screening tests show that you are not eligible to take part in the study, you will not be enrolled. Other treatment options will be discussed with you. Study Groups: If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to receive either chemotherapy without radiation (Group A) or chemotherapy with radiation (Group B). You will have an equal chance of being in either group. Pre-Surgery Study Drug Administration: * If you are in Group A, you will receive gemcitabine over about 90 minutes 1 time each week (Days 1, 8, 15, 22, 29, 36 \[+/- 2 Days\]. You will take erlotinib by mouth, with water, 1 hour before eating or 2 hours after eating 1 time daily on Days 1-42. * If you are in Group B, you will receive gemcitabine over about 40 minutes 1 time each week (Days 1, 8, 15, 22, 29, 36, \[+/- 2 Days\]). You will take erlotinib by mouth, with water, 1 hour before eating or 2 hours after eating 1 time daily on Days 1-42. You will also receive radiation therapy 1 time each day for 5 days in a row (Monday through Friday) for 5 1/2 weeks starting on Day 1. You will sign a separate consent form for the radiation therapy. If any days of radiation therapy are missed, you will make up the missed day(s) at the end of therapy so you receive the full amount of radiation therapy. Post-Surgery Study Drug Administration: For all participants, starting within 12 weeks after the surgery, you will receive gemcitabine over 100 minutes on Days 1, 8, and 15 \[+/- 2 Days\]) of each 4 weeks cycle. You will also take erlotinib by mouth with water 1 hour before eating or 2 hours after eating 1 time daily for 4 weeks. You may be able to receive your postoperative therapy closer to home by an outside cancer doctor. This will be up to the treating cancer doctor at M. D. Anderson. A research nurse will contact you at least every other week by telephone. Participants who need radiation treatment will only be allowed to receive radiation treatment at M. D. Anderson Cancer Center. Surgery: All participants will have chest x-rays and CT scans performed approximately 4 weeks after the last dose of the study drug combination to check the status of the disease. If the disease has not gotten worse, and the study doctor thinks it is in your best interest, you will be scheduled to have surgery to remove the pancreas and duodenum. You will sign a separate consent form for the surgery. If you are not found to be eligible for surgery, your participation on this study end at this time. Length of Study: You will be taken off study early if the disease gets worse, you experience intolerable side effects, or the study doctor thinks it is no longer in your best interest to continue to receive the study drug. You will remain on the study for approximately 10 months. Follow-Up Visit: After your participation on this study is complete, you will have a chest x-ray and a CT scan every 4 months for 2 years. This is an investigational study. Gemcitabine and Erlotinib are both FDA and commercially available, but their use together with radiation therapy is investigational. Up to 190 patients will take part in the study. All will be enrolled at M. D. Anderson.