Test the safety, immune response and efficacy of GVAX pancreas vaccine (with cyclophosphamide) and CRS-207 compared to GVAX pancreas vaccine (with cyclophosphamide) alone in adults who have failed or refused prior treatment for metastatic pancreatic cancer.

Inclusion Criteria:

• Have histologically proven malignant adenocarcinoma of the pancreas; measurable disease is not required. (Subjects with mixed histology will be included if the predominant component is adenocarcinoma. Subjects must have metastatic disease.)
• Have received or refused at least one chemotherapy regimen
• At least 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Anticipated life expectancy of >12 weeks
• For women and men of childbearing potential, a medically acceptable method of highly effective contraception (oral hormonal contraceptive, condom plus spermicide, or hormone implants) must be used throughout the study period and for 28 days after their final vaccine administration. (A barrier method of contraception must be employed by all subjects [male and female], regardless of other methods.)
• Be willing and able to give written informed consent, and be able to comply with all study procedures
• Have adequate organ function as defined by specified laboratory values

Exclusion Criteria:

• Currently have or have history of certain study-specified heart, liver, kidney, lung, neurological, immune or other medical conditions
• Known history or evidence of brain metastases
• Have any evidence of hepatic cirrhosis or clinical or radiographic ascites
• Have clinically significant and/or malignant pleural effusion
• Known or suspected hypersensitivity to any component of GVAX Pancreas vaccine or CRS-207, or known allergy to both penicillin and sulfa
• Received an investigational product within 28 days of study treatment or planned to receive within 28 days after vaccine administration
• Used any systemic steroids within 28 days of study treatment
• Use more than 3 g/d of acetaminophen
• Prosthetic joint or other artificial implant or device that cannot be easily removed (there are some exceptions)
• Major surgery or significant traumatic injury (or unhealed surgical wounds) occurring within 28 days prior to receiving study drug, or planned surgery requiring general anesthesia
• Infection with HIV or hepatitis B or C at screening
• Any immunodeficiency disease or immunocompromised state or active autoimmune disease or history of autoimmune disease requiring systemic steroids or other immunosuppressive treatment
• Be pregnant or breastfeeding
• Unable to avoid close contact with another individual known to be at high risk of listeriosis (e.g., newborn infant, pregnant woman, HIV-positive individual) during the course of CRS-207 treatment until completion of antibiotic regimen
• Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures