Proglumide and Chemotherapy for Metastatic Pancreatic Cancer

Inclusion Criteria: 1. Written informed consent and any locally-required authorization (e.g., HIPAA in the USA) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations 2. Age \> 18 years at time of study entry. 3. Adequate normal organ and marrow function as defined below: * Hemoglobin ≥ 9.0 g/dL * Absolute neutrophil count (ANC) \> 1500 per mm3 * Platelet count ≥100,000 per mm3) * Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). * AST and ALT ≤2.5 x ULN of normal unless liver metastases are present, in which case it must be ≤5x ULN * Creatinine clearance (CL) \>60 mL/min using the Cockroft-Gault formula. 4. Evidence of post-menopausal status or negative urine or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments, or if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). 5. Patients must have measurable disease by RECIST v1.1 and disease amenable to serial biopsy. 6. Subjects may not have received prior therapy with GEM/NAB-P. 7. Patients must have metastatic pancreatic ductal adenocarcinoma with adenocarcinoma as the dominant histology (biopsy-proven, primary tumor biopsy is acceptable for eligibility) 8. No prior systemic treatment contain GEM or NAB-P. 9. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. Exclusion Criteria: 1. Subjects with a concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of adequately treated basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer, or localized prostate cancer following definitive therapy. 2. Subjects with uncontrolled cardiovascular diseases (congestive heart failure, symptoms of coronary artery disease, cardiac arrhythmias) or who have suffered a myocardial infarction in the preceding 6 months. 3. Blood anticoagulation that cannot be safely stopped for biopsy. 4. Subjects with poorly controlled medical conditions including asthma, chronic obstructive pulmonary disease, diabetes, seizure disorders, hepatic or renal failure. 5. Pregnant or nursing women. 6. Men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device \[IUD\], or abstinence) prior to study entry, for the duration of study participation, and for 6 months thereafter. 7. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. 8. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable. 9. History of allogenic organ transplantation. 10. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea or inability to digest and absorb pills, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent 11. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). * Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. * Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. * Testing for tuberculosis, hepatitis B and C and HIV is not a requirement for screening for the clinical trial. 12. Receipt of live attenuated vaccine within 30 days prior to the first dose of investigational drug. Note: Patients, if enrolled, should not receive live vaccine while receiving IP and up to 30 days after the last dose of IP. 13. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of proglumide therapy. 14. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. 15. Patient is unable to swallow pills or has a malabsorption syndrome that would not enable the patient to properly absorb proglumide.