Combination Chemotherapy Followed by Ipilimumab and Vaccine Therapy in Treating Patients with Metastatic Pancreatic Cancer

Inclusion Criteria

• Have histologically proven adenocarcinoma of the pancreas; patients with mixed histology will be excluded
• Have stable metastatic pancreatic cancer after receiving 8-12 doses of FOLFIRINOX (measurable disease is not required)
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Karnofsky > 60%)
• Life expectancy of greater than 3 months
• White blood cells (WBC) >= 3500/uL
• Absolute neutrophil count (ANC) >= 1500/uL
• Platelets >= 90 x 10^3/uL
• Hemoglobin >= 9 g/dL
• Total bilirubin =< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (=< 5 x ULN for patients with documented liver metastases)
• Creatinine =< 2.0 x ULN
• Women of child-bearing potential (WOCBP) 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; WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea >= 12 consecutive months; or women on hormone replacement therapy [HRT] with documented serum follicle stimulating hormone [FSH] level > 35 mIU/mL); even women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential
• Ability to understand and the willingness to sign a written informed consent document
• Oxygen saturation on room air > 92 % by pulse oximetry; (patients on intermittent or continuous supplemental oxygen are not allowed)

Exclusion Criteria

• Patients in whom histologic diagnosis is not consistent with ductal adenocarcinoma such as adenosquamous, squamous cell, colloid, islet cell, serous or mucinous cystadenoma or cystadenocarcinoma, carcinoid, small or large cell carcinoma, intraductal oncocytic papillary neoplasms (IOPN), osteoclast-like giant cell tumors, acinar cell carcinoma, pancreatoblastoma, solid pseudopapillary tumors, undifferentiated small cell carcinoma and non-epithelial tumors (sarcomas, gastrointestinal [GI] stromal tumor, lymphoma)
• Patients who have adenocarcinomas of the ampulla, distal bile duct, and duodenum
• Patients who have had surgery within 4 weeks of dosing of investigational agent, excluding minor procedures (dental work, skin biopsy, etc), celiac plexus block, and biliary stent placement
• Patients who have been off of FOLFIRINOX more than 70 days prior to treatment on study
• Patients who have had prior chemotherapy for metastatic pancreatic cancer (other than FOLFIRINOX); prior radiation is allowed; chemotherapy for non-metastatic disease is allowed
• Patients with a history of prior treatment with ipilimumab, anti-programmed cell death 1 (PD1) antibody, cluster of differentiation (CD)137 agonist or anti-CD 40 antibody
• Patients who have received any non-oncology live vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of ipilimumab/vaccine)
• Patients who are receiving any other investigational agents
• Patients who have received any of the following concomitant therapy: interleukin (IL)-2, interferon; immunosuppressive agents; or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses)
• Autoimmune disease: patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn’s disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener’s granulomatosis]); central nervous system (CNS) or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis, multiple sclerosis); patients with thyroid disease will be allowed; autoimmune diagnoses not listed here must be approved by the protocol chair, following discussion with the study sponsor and Cancer Therapy Evaluation Program (CTEP)
• Patients with known immune impairment who may be unable to respond to anti-cytotoxic T-lymphocyte antigen 4 (CTLA 4) antibody
• Patients with known brain metastases should be excluded from early clinical trials
• Patients with radiographic ascites that is apparent on physical exam or requiring medical intervention (medication or procedures) in the 2 months prior to enrollment
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or obscure the interpretation of adverse events (AEs)
• Patients with a known or suspected hypersensitivity to GM-CSF, hetastarch, corn, dimethyl sulfoxide (DMSO), fetal bovine serum, or trypsin (porcine origin)
• Patients with chronic human immunodeficiency virus (HIV), hepatitis B or hepatitis C infections should be excluded
• WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of investigational product
• Women who are pregnant or breastfeeding
• Women with a positive pregnancy test on enrollment or prior to investigational product administration
• Sexually active fertile men not using effective birth control if their partners are WOCBP