Tolfenamic Acid, Gemcitabine and Radiation for Locally Advanced or Metastatic Pancreatic Cancer Requiring Radiation

Primary Inclusion Criteria: 1. Patients must have histologically or cytologically confirmed: 1. Locally advanced (potentially resectable) pancreatic adenocarcinoma requiring neoadjuvant radiation or 2. Locally advanced (nonresectable) or metastatic pancreatic adenocarcinoma requiring definitive or palliative radiation therapy 2. Patients may have either measurable or non-measurable disease (according to RECIST criteria, Version 1.1). 3. Age ≥ 18 years 4. ECOG performance status of 0 or 1. 5. A life expectancy of at least 12 weeks. 6. No other concurrent radiotherapy, chemotherapy or immunotherapy. 7. A minimum of 4 weeks must have elapsed since completion of any prior chemotherapy or immunotherapy. 8. Patient must have: 1. Absolute neutrophil count (ANC) ≥1,000/mm3 2. Platelets ≥100,000/mm3 3. Hemoglobin ≥10 g/dL \[Transfusion to meet the hemoglobin requirement is acceptable\] 4. Serum creatinine ≤ 1.5 X ULN 5. Total bilirubin ≤ 1.5 X ULN 6. Aspartate aminotransferase (AST) ≤ 2.5 X ULN 7. Alanine aminotransferase (ALT) ≤ 2.5 X ULN 8. Alkaline phosphatase ≤ 2.5 X ULN 9. PT/INR ≤ 1.5 X ULN 10. aPTT ≤ 1.5 X ULN 11. Urine Protein ≤ Grade 1 9. For patients on warfarin: Must have maintained a stable INR on a stable dose of warfarin for at least 4 weeks prior to start of treatment. Primary Exclusion Criteria: 1. Patients who have received prior radiation for their current malignancy at the location of interest. 2. Patients who have not recovered (to Grade 1 or less) from adverse events, other than alopecia and neuropathy, caused by previously administered chemotherapeutic agents, at the discretion of the PI/treating physician. 3. Tolfenamic acid use concurrent with, or within 8 weeks prior to the diagnosis of pancreatic cancer. 4. Current use of any non-steroidal anti-inflammatory agents (NSAIDs), including aspirin, (other than tolfenamic acid) within 4 weeks prior to the start of active treatment. 5. Previous history of hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin or other NSAIDs. 6. History of recurrent peptic ulcer/hemorrhage (two or more distinct episodes). 7. History of gastrointestinal bleeding or perforation related to previous use of NSAIDS. 8. New York Heart Association Functional Classification of 3 or 4. 9. Known autoimmune disease that could preclude the use of radiation, at the discretion of the treating physician. 10. History or evidence of CNS disease (e.g., any brain metastases, primary brain tumor, seizures not controlled with standard medical therapy, or history of stroke). 11. Known HIV positive. 12. Active systemic infection requiring parenteral antibiotic therapy. 13. Receiving systemic steroid therapy. (Inhaled steroid therapy is allowable.) 14. History of other malignancies within the last 5 years with the exception of non- melanoma skin cancer or cervical cancer in situ that has been successfully treated.