Chemotherapy and Radiation Therapy Before Surgery Followed by Gemcitabine in Treating Patients with Pancreatic Cancer

Pre-Registration Eligibility Criteria * Documentation of Disease and Radiographic Staging * Cytologic or histologic proof of adenocarcinoma of the pancreatic head or uncinate process * Objective radiographic staging with a) contrast-enhanced, helical thin-cut computed tomography (CT)/magnetic resonance imaging (MRI) scan of the abdomen and b) CT scan/MRI of the chest * Note: echoendoscopic staging will be permitted as an adjunctive modality, but all stage definitions below will be determined using CT/MRI as outlined below. In the event echoendoscopic stage and CT/MRI stage are discordant, the CT/MRI stage will be used. Significant discordance should be discussed with the study principal investigator (PI) prior to enrollment * Borderline resectable primary tumor, defined by the presence of any one or more of the following on CT/MRI, and confirmed by central radiographic review: * An interface between the primary tumor and the superior mesenteric vein or portal vein (SMV-PV) measuring ≥ 180 degrees of the circumference of the vessel wall * Short-segment occlusion of the SMV-PV with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction * Short segment interface (of any degree) between tumor and hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and reconstruction * An interface between the tumor and superior mesenteric artery (SMA) measuring \< 180 degrees of the circumference of the vessel wall * No potentially resectable disease defined as primary tumors with all of the following: * An interface between the primary tumor and the superior mesenteric vein or portal vein (SMV-PV) measuring \< 180 degrees of the circumference of the vessel wall * No radiographic interface between the tumor and the (superior mesenteric artery) SMA, hepatic artery or celiac axis * No radiographic evidence of metastatic disease * No metastatic disease defined as any one or more of the following: * Suspicious lymphadenopathy outside the standard surgical field (i.e., aortocaval nodes, distant abdominal nodes) * Radiographic evidence for metastatic disease in distant organs, such as masses in distant organs or ascites * No locally advanced and/or unresectable disease clearly defined by any one or more of the following by CT/MRI: * An interface between the tumor and the SMA measuring ≥ 180 degrees of the circumference of the vessel wall * No interface between the tumor and the aorta * Occlusion of the SMV or portal vein without a sufficient cuff of normal vein above and below the level of obstruction with which to perform venous reconstruction * Long-segment interface (of any degree) between the tumor and the common hepatic artery or its major tributaries with insufficient artery proximal and distal to the interface to perform reconstruction * No prior chemotherapy or chemoradiation for pancreatic cancer * No patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for ≥ 3 years * Baseline peripheral sensory neuropathy must be grade \< 2 * No patients with known Gilbert's Syndrome or homozygosity for UGT1A1\*28 polymorphism * No history of pulmonary embolism in the past 6 months * Age ≥ 18 years of age * Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status 0-1 * Pregnancy/Nursing Status: Non-pregnant and non-breast-feeding. Female participants of child-bearing potential must have a negative urine or serum pregnancy test prior to registration. Perimenopausal participants must be amenorrheic \> 12 months to be considered not of childbearing potential. * Required Pre-Registration Laboratory Values: * Granulocytes ≥ 2,000/ul * Hemoglobin \> 9 g/dL * Platelets ≥ 100,000/ul * Albumin \> 3.0 g/dL * Creatinine ≤1.5 x upper limit of normal (ULN) Registration Eligibility Criteria * Confirmation of pre-registration eligibility criteria as described under "Documentation of Disease and Radiographic Staging" by the Alliance Central Radiographic Review * Required Registration Laboratory Values: * Bilirubin ≤2 mg/dl * AST (SGOT) \& ALT (SGPT) ≤ 2.5 x ULN