TAS-102 (Lonsurf) in Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma Post First Line Chemotherapy (UF-STO-PANC-003)

Inclusion Criteria: * Clinical diagnosis of adenocarcinoma of the pancreas, with pathologic confirmation of adenocarcinoma. * Measurable disease per RECIST 1.1 criteria * Metastatic or locally advanced unresectable disease. Subjects without clear evidence of distant metastatic disease will be presented at multidisciplinary tumor board for discussion of disease resectability. * Refractory or intolerant to 1 or 2 prior regimens of standard chemotherapy for metastatic or locally advanced pancreatic cancer * TAS102 will be planned to start after disease progression on first-or second line chemotherapy, provided any prior chemotherapy-related toxicities have resolved to less than or equal to Grade 1 or baseline within 28 days of the date the subject signs the informed consent form. Grade 2 or greater toxicities including alopecia, skin pigmentation,and platinum induced neurotoxicity/neuropathy are acceptable for starting on trial, as these toxicities do not preclude treatment with TAS102 * ECOG Performance Status of 0-2 * Capacity to understand and sign the informed consent document * Able to take medications orally * Life expectancy at least 12 weeks * Age at least 18 years * Patients on anticoagulation need to have no evidence of uncontrolled bleeding and be on a stable anticoagulation dose for at least 2 weeks prior to the date the subject starts study drug. * Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 3 months after the last dose of study drug to minimize the risk of pregnancy. Prior to signing the informed consent form, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. * WOCBP include any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who is not post-menopausal. Post-menopause is defined as: * Amenorrhea that has lasted for ≥ 12 consecutive months without another cause, or * For women with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL. * Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 3 months following the last dose of study drug. * Baseline laboratory values (bone marrow, renal, hepatic) must include: * Adequate bone marrow function: 1. Absolute neutrophil count \>1500/mm3 2. Platelet count \>75,000/mm3 3. HGB equal to or greater than 7g/dL * Renal function: a. Serum creatinine ≤ 1.5 mg * Hepatic function: 1. Total bilirubin ≤ 1.5 mg/dL 2. AST and ALT equal to or less than 3 times the upper limit of normal for patients without hepatic involvement, or AST and ALT equal to or less than 5 times the upper limit of normal for patients with hepatic involvement 3. Serum calcium ≤ 12 mg/dl Exclusion Criteria: * Pregnant or lactating females * Previously taken TAS-102 * Myocardial infarction or ischemia within the 6 months before first dose of study drug * Uncontrolled' clinically significant dysrhythmia * Intervention for ascites or pleural effusions within 4 weeks before first dose of study drug * Previous surgery and/or radiotherapy may have been performed 2 or more weeks prior to the date the subject starts study treatment, provided that it was to a non-target lesion and there is still evidence of target lesion disease progression radiographically or intolerance to first- or second-line chemotherapy. * Major surgery within 4 weeks before first dose of study drug (the surgical incision should be fully healed prior to study medication administration). * Any anticancer therapy within 3 weeks before first dose of study drug. * Extended field radiation within 4 weeks before first dose of study drug or limited field radiation within 2 weeks before first dose of study drug. * Any investigational agent received within prior 4 weeks before first dose of study drug * Subjects must not have more than one active malignancy at the time of enrollment * Unresolved NCI-CTCAE toxicity grade 2 or higher attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation, and platinum induced neurotoxicity) * Any co morbid condition that' in the view of the attending physician' renders the patient at high risk from treatment complications including but not limited to chronic infections, uncontrolled diabetes, congestive heart failure according to the NYHA criteria, untreated brain metastases, liver or renal failure, gastrointestinal hemorrhage. * Known untreated or unstable brain metastases or leptomeningeal disease * Active infection * Prisoners or subjects who are involuntarily incarcerated or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.