A Modified Conditionally Replicative Adenovirus Vector (RGDCRAdCOX2F) for the Treatment of Pancreatic Cancer

Inclusion Criteria

• Histologically documented pancreatic adenocarcinoma that is confined to the pancreas and regional lymph nodes after staging by CT or MRI and endoscopic ultrasound.
• One prior line of therapy is permitted (i.e. neo-adjuvant therapy); however, at least 4 weeks must have elapsed between the last dose of drug and the injection of RGDCRAdCOX2F.
• Must be able to tolerate esophagogastroduodenoscopy (EGD) and the tumor must be accessible by endoscopic ultrasound. Participants will be excluded if obtaining biopsies are deemed unsafe or not feasible. * The tumor for RGDCRAdCOX2F injection should not encase or be inseparable from vital structures such as major nerves or blood vessels. However, tumor involvement of the portal/mesenteric veins and celiac/mesenteric arteries is permitted.
• If surgical resection is planned, must be scheduled for resection 10 days (± 1 day) after injection of RGDCRAdCOX2F.
• If prior chemotherapy, must be at least 4 weeks from the last treatment.
• Biliary obstruction must be relieved by stenting or surgical bypass prior to enrollment.
• Age 18 years of age or older at the time of consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• White blood cells (WBC) > 3,000 /mm^3 (within 14 days prior to day 1 [day of RGDCRAdCOX2F injection]).
• Absolute neutrophil count (ANC) > 1,500 /mm^3 (within 14 days prior to day 1 [day of RGDCRAdCOX2F injection]).
• Platelets > 100,000 /mm^3 (within 14 days prior to day 1 [day of RGDCRAdCOX2F injection]).
• International normalized ratio (INR) ≤ 1.5 or partial thromboplastin time (PTT) within normal limits (WNL) of the institution (within 14 days prior to day 1 [day of RGDCRAdCOX2F injection]).
• Estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m^2 or serum creatinine < 2.0 (within 14 days prior to day 1 [day of RGDCRAdCOX2F injection]).
• Serum transaminases < 2.5 x upper limits of normal (within 14 days prior to day 1 [day of RGDCRAdCOX2F injection]).
• Normal serum bilirubin (within 14 days prior to day 1 [day of RGDCRAdCOX2F injection]).
• Normal cardiac and pulmonary function based on history and physical exam. If there is clinical concern of significant cardiopulmonary disease, participant must have an echocardiogram documenting a left ventricular ejection fraction (LVEF) of > 45% and resting oxygen saturation of > 90% on room air within 14 days prior to day 1.
• Participants with partners of childbearing potential must be willing to use at least two forms of effective birth control (one form must be a barrier method) for at least 1 month after day 1. Persons are considered to be of childbearing potential unless one or the following applies: * Is postmenopausal, defined as no menses for at least 12 months without an alternative medical cause. * Considered permanently sterile. Permanent sterilization includes hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy.
• Voluntary written consent prior to the performance of any research related activity.

Exclusion Criteria

• Pregnant or breastfeeding. Persons of child-bearing potential must have a negative pregnancy test (serum or urine) with 14 days of study enrollment.
• Other pancreatic malignancies (e.g., neuroendocrine tumors and mucinous cystic) and adenocarcinomas of the ampulla, bile ducts, and duodenum.
• Tumors in mucosal regions or close to an airway, major blood vessel, or spinal cord that in the opinion of the enrolling investigator could cause occlusion or compression in the case of tumor swelling or erosion into a major vessel in the case of necrosis. However, the following exception applies: * Tumors with involvement of the portal/mesenteric veins and celiac/mesenteric arteries are permitted.
• Known history of human immunodeficiency virus (HIV) infection.
• Known history of or active acute or chronic active hepatitis B or C infection.
• Serious concurrent infection or medical illness, which in the enrolling investigator’s opinion would jeopardize the ability of the participant to receive the treatment outlined in this protocol with reasonable safety.
• Requires immunosuppression ≥ 10mg/day of prednisone for more than 1 week.
• History of or active known or suspected autoimmune disease, or a syndrome that requires systemic or immunosuppressive agents.
• Disease beyond the regional lymph nodes.
• Active diffuse pancreatitis.
• Active inflammatory conditions.
• Prior gastrojejunostomy.