Tosedostat With Capecitabine in Patients With Metastatic Pancreatic Adenocarcinoma

Inclusion Criteria: * Histologically or cytologically proven metastatic or inoperable pancreatic adenocarcinoma. * Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>10 mm with CT scan or MRI, as \>20 mm by chest x-ray, or \>10 mm with calipers by clinical exam. * Must have progressed on, been intolerant to, or refused gemcitabine-based therapy. * At least 18 years of age. * ECOG performance status ≤ 2 * Normal bone marrow and organ function as defined below: * Absolute neutrophil count ≥ 1,000/mcl * Platelets ≥ 100,000/mcl * Total bilirubin ≤ 2.0 mg/dL * Creatinine ≤ 2.0 mg/dL * AST or ALT ≤2.5 IULN (≤5X IULN if liver metastases are present) * Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. * Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable). Exclusion Criteria: * Chemotherapy \< 2 weeks prior to the first planned dose of study treatment. * Radiotherapy \< 3 weeks prior to the first planned dose of study treatment. * A history of other malignancy ≤ 2 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix. * Currently receiving any other investigational agents. * Known brain metastases. Patients with known brain metastases must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. * A history of allergic reactions attributed to compounds of similar chemical or biologic composition to tosedostat or capecitabine or other agents used in the study. * Previous treatment with any aminopeptidase inhibitor. * Previous exposure to either 5-FU or capecitabine at a systemic dose except for use in concurrent chemoradiation. * Known dihydropyrimidine dehydrogenase (DPD) deficiency or severe renal impairment (creatinine clearance \< 30 mL/min by Cockcroft-Gault formula), as this would preclude use of capecitabine. * Significant cardiovascular disease defined as: * Myocardial infarction within 6 months of screening. * Unstable angina pectoris * Uncontrolled or clinically significant arrhythmia Grade ≥ 2 * LVEF ≤ below institutional limits at screening * Congestive heart failure NYHA class III or IV * Presence of clinically significant valvular heart disease * Baseline troponin I or T \> IULN and b-type natriuretic peptide \> IULN. * Prior exposure to cardiotoxic agent, such as anthracyclines, within 3 months of enrollment. * Patient must have a QTc interval on ECG ≤ 0.48 seconds by Bazett's calculation at screening. * Patient may not be taking any drugs that prolong the QT/QTc interval. If patient is on any of these drugs, patient may enroll in the study if the drugs can be discontinued for at least 5 half-lives prior to the first dose of tosedostat and capecitabine. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant and/or breastfeeding. Patients that are of childbearing age must have a negative pregnancy test at screening and agree on using contraception during the duration of the study. * Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with tosedostat or capecitabine. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.