Inclusion Criteria

• Age ≥18 years old
• Patients with unresectable, locally advanced adenocarcinoma of the pancreas proven by biopsy or cytology (defined as direct extension to the SMA and/or celiac axis with absence of a fat plane between the low-density tumor and these arterial structures, or loss of patent superior mesenteric-portal vein confluence), who have not received previous treatment for pancreatic cancer. Patients who have been surgically explored and deemed unresectable on that basis are eligible, provided other entry criteria are met
• Informed consent
• Karnofsky performance status = or >70%
• Life expectancy greater than 3 months
• Measurable disease

Exclusion Criteria

• Metastatic (stage IV) disease (including involvement of the colon, adrenals, or kidney, or radiographic evidence of peritoneal seeding)
• Patients with ascites detected by CT, US or MRI
• Patients with bulky celiac adenopathy (i.e., > 2.5 cm)
• Diagnosis of islet cell tumor of the pancreas, lymphoma of the pancreas
• History of other malignancy in the past 2 years except carcinoma in situ of the cervix or bladder, non-melanomatous skin cancer or localized early stage prostate cancer
• Previous chemotherapy or radiation for pancreatic cancer or previous radiation to the target field
• Liver enzymes >3 x ULN (ALT, AST, total bilirubin, alkaline phosphatase)
• Coagulopathy (INR >1.5, PTT ratio >1.5)
• Renal insufficiency (serum creatinine >2.0 mg/dL)
• Significant anemia (e.g. hematocrit <28% or hemoglobin <9 g/dL) (may have RBC transfusion), or thrombocytopenia (platelet count <100,000/µL); or neutropenia (ANC <1500/µL)
• Patients with clinically significant pancreatitis within 12 weeks of treatment
• Pancreatic pseudocyst
• Contraindication to both percutaneous- and endoscopic- guided delivery
• Patients with history of deep venous thrombosis or pulmonary embolus
• Patients with doppler evidence of deep venous thrombosis at screening
• Patients with history of coagulopathy or known thrombophilic disorders
• Patients receiving hormone replacement therapy including oral contraceptives within 2 weeks prior to Day 1.
• Clinical evidence of active infection of any type, including hepatitis B or C virus
• Pregnant or lactating women. It is recommended that both men and women use condoms or another barrier method of birth control for at least 8 weeks following the last administration of TNFerade™ biologic and some form of birth control for at least 1 year
• Experimental medications within the last 4 weeks prior to Day 1
• Surgery within the last 4 weeks prior to Day 1 (if patient was ambulatory within 48 hours of surgery, patient may be considered eligible)
• Chronic systemic corticosteroid use at superphysiologic doses (greater than 10mg prednisone per day or equivalent)
• Significant concurrent medical or psychiatric illness which, in the opinion of the investigator, would interfere with the patient's ability to participate in the trial

Please note that there are additional entry criteria. The study center will determine if you meet all criteria. If you do qualify to participate, study personnel will explain the study and answer any questions you may have. You can decide whether or not you wish to participate but if you do not qualify for this trial, study staff will explain the reasons. Please contact your local center listed below, or call the toll free PACT study line for assistance at 1-888-344-6096