A Randomized, Phase II/III, Study of TNFerade™ Biologic With 5-FU and Radiation Therapy for First-line Treatment of Unresectable Locally Advanced Pancreatic Cancer

Inclusion Criteria

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