Role of Proglumide in Combination with Gemcitabine and Nab Paclitaxel on the Tumor Microenvironment in Patients with Metastatic Pancreatic Cancer

Inclusion Criteria

• In this study, subjects are eligible if they have metastatic histological or cytologic confirmation of adenocarcinoma of the pancreas
• Both male and female patients of at least 18 years of age will be eligible
• Patients must have an ECOG (Eastern Cooperative Oncology Group) Performance status 0-or 1 and an estimated life expectancy of > 3 months
• Patients or legal representative must be able to give written consent.
• Female patients who are menopausal, or of childbearing age that are surgically sterile or practicing birth control (chemical or mechanical) are eligible. All females of child-bearing potential must have a serum pregnancy test upon entry into the study. At least four weeks must pass from significant surgery and the subject must be physically recovered.
• Written informed consent and any locally-required authorization (e.g., Health Insurance Portability and Accountability Act [HIPAA] in the United States of America [USA], European Union [EU] Data Privacy Directive in the EU) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations
• Age ≥ 18 years at time of study entry
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1500 per mm^3
• Platelet count ≥ 100,000 per mm^3
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN of normal unless liver metastases are present, in which case it must be ≤ 5x ULN
• Creatinine clearance (CL) > 40 mL/min using the Cockroft-Gault formula
• Evidence of post-menopausal status or negative urinary 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)
• Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 and disease amenable to serial biopsy
• Subjects may not have received prior therapy with gemcitabine/NAB-P
• Pregnant or nursing women

Exclusion Criteria

• Subjects with a concurrent malignancy or malignancy within 5 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
• Subjects with uncontrolled cardiovascular diseases (congestive heart failure, symptoms of coronary artery disease, cardiac arrhythmias) or have suffered a myocardial infarction in the preceding 6 months
• Blood anticoagulation that cannot be safely stopped for biopsy
• Prior anti-tumor therapy with gemcitabine/ NAB-P and not prior anti-cancer therapy within 1-days prior to the biopsy and first dose of study drug
• Subjects with poorly controlled medical conditions including asthma, chronic obstructive pulmonary disease, diabetes, seizure disorders, known brain metastases, hepatic or renal failure
• 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 and for the duration of study participation
• Any concurrent chemotherapy, investigational product (IP), biologic, or hormonal therapy for cancer treatment
• 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
• History of allogenic organ transplantation
• 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 psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events (AEs) or compromise the ability of the patient to give written informed consent
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice), hepatitis B (known positive hepatitis B virus [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 ribonucleic acid (RNA)
• 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 whilst receiving IP and up to 30 days after the last dose of IP
• 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
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
• Known allergy or hypersensitivity to proglumide or any excipient
• 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