Proglumide and Chemotherapy for Metastatic Pancreatic Cancer

Inclusion Criteria:

1. Written informed consent and any locally-required authorization (e.g., HIPAA in theUSA) 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 whichcase 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 forfemale pre-menopausal patients. Women will be considered post-menopausal if theyhave been amenorrheic for 12 months without an alternative medical cause. Thefollowing age-specific requirements apply: Women <50 years of age would be considered post-menopausal if they have beenamenorrheic for 12 months or more following cessation of exogenous hormonaltreatments, or if they have luteinizing hormone and follicle-stimulating hormonelevels in the post-menopausal range for the institution or underwent surgicalsterilization (bilateral oophorectomy or hysterectomy).

5. Patients must have measurable disease by RECIST v1.1 and disease amenable to serialbiopsy.

6. Subjects may not have received prior therapy with GEM/NAB-P.

7. Patients must have metastatic pancreatic ductal adenocarcinoma with adenocarcinomaas the dominant histology (biopsy-proven, primary tumor biopsy is acceptable foreligibility)

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 thestudy including undergoing treatment and scheduled visits and examinations includingfollow up.

Exclusion Criteria:

1. Subjects with a concurrent malignancy or malignancy within 3 years prior to startingstudy drug, with the exception of adequately treated basal or squamous cellcarcinoma, non-melanomatous skin cancer or curatively resected cervical cancer, orlocalized 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 amyocardial 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, chronicobstructive pulmonary disease, diabetes, seizure disorders, hepatic or renalfailure.

5. Pregnant or nursing women.

6. Men or women of childbearing potential who are unwilling to employ adequatecontraception (condoms, diaphragm, birth control pills, injections, intrauterinedevice [IUD], or abstinence) prior to study entry, for the duration of studyparticipation, 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 tothe first dose of IP. Note: Local surgery of isolated lesions for palliative intentis acceptable.

9. History of allogenic organ transplantation.

10. Uncontrolled intercurrent illness, including but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, uncontrolled hypertension, unstableangina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronicgastrointestinal conditions associated with diarrhea or inability to digest andabsorb pills, or psychiatric illness/social situations that would limit compliancewith study requirement, substantially increase risk of incurring AEs or compromisethe ability of the patient to give written informed consent

11. Active infection including tuberculosis (clinical evaluation that includes clinicalhistory, physical examination and radiographic findings, and TB testing in line withlocal 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 ofhepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible.

• Patients positive for hepatitis C (HCV) antibody are eligible only ifpolymerase chain reaction is negative for HCV RNA.

• Testing for tuberculosis, hepatitis B and C and HIV is not a requirement forscreening for the clinical trial.

12. Receipt of live attenuated vaccine within 30 days prior to the first dose ofinvestigational drug. Note: Patients, if enrolled, should not receive live vaccinewhile 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 ofreproductive potential who are not willing to employ effective birth control fromscreening 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 drugexcipients.

15. Patient is unable to swallow pills or has a malabsorption syndrome that would notenable the patient to properly absorb proglumide.