The primary purpose of this study is to assess the safety and feasibility of giving TNFerade™ with 5-FU and radiation therapy to patients with locally advanced, unresectable pancreatic cancer that have not received prior treatment. TNFerade™ is a replication deficient (E1, E3 and E4 deleted) adenovirus vector containing the gene for TNF-alpha controlled by a radiation inducible promoter. This allows the expression of TNF-alpha to be greatest in the area receiving radiation. TNF-alpha is a potent cytokine that has been shown to have potent anti-cancer activities but, due to systemic toxicity, could not be delivered at effective doses. TNFerade™ is a novel way of selective delivery of TNF-alpha to tumor cells.

TNFerade™ will be delivered once a week for five weeks by direct intratumoral injection by using CT or ultrasound guidance or Endoscopic Ultrasound. 5-FU (200 mg/m2/day) will be delivered via continuous infusion 5 days/week for the duration of radiation treatments. The dose of radiation delivered will be 50.4 Gy in 1.8 Gy fractions for 5.5 weeks.

Condition	Treatment or Intervention	Phase
Pancreatic Cancer	Gene Transfer: TNFerade	Phase II

Ages Eligible for Study:  18 Years   -   80 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

• Age between 18 and 80 years old
• Biopsy proven locally advanced adenocarcinoma of the pancreas assessed to be unresectable, who have not received previous treatment for pancreatic cancer
• Signed informed consent
• Karnofsky performance status equal or greater to 70%
• Life expectancy greater than 3 months

Exclusion Criteria

• 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
• Metastatic (stage IV) disease
• Liver enzymes greater than 3 x ULN (ALT, AST, bilirubin, alkaline phosphatase)
• Coagulopathy (INR greater than 1.5, PTT ratio grater than 1.5)
• Renal insufficiency (serum creatinine greater than 2.0 mg/mL)
• Significant anemia or thrombocytopenia or leukopenia
• Pancreatitis
• Contraindication to EUS-guided and percutaneous-guided delivery
• Pancreatic pseudocyst
• Clinical evidence of active infection of any type, including hepatitis B or C virus
• Pregnant or lactating women
• Experimental medications within the last 4 weeks prior to Day 1
• Chronic systemic corticosteroid use, orally or parenterally administered
• Significant concurrent medical or psychiatric illness as defined by the investigator

California
      UCLA Department of Medicine, Los Angeles,  California,  90095-7077,  United States; Recruiting
      Palo Alto VA Health Care Systems, Palo Alto,  California,  94304,  United States; Suspended
      San Francisco General Hospital, San Francisco,  California,  94110,  United States; Recruiting
      University of California, Irvine, Orange,  California,  92868,  United States; Recruiting
      UCSD Cancer Center, La Jolla,  California,  92093-0064,  United States; Recruiting
Florida
      Tampa General Hospital, Tampa,  Florida,  33606,  United States; Recruiting
Illinois
      The Universtiy of Chicago Medical Center, Chicago,  Illinois,  60637,  United States; Recruiting
Missouri
      Washington University, St. Louis,  Missouri,  63110,  United States; Recruiting
New York
      Roswell Park Cancer Institute, Buffalo,  New York,  14263,  United States; Recruiting
      Weill Cornell Medical Center, New York,  New York,  10021,  United States; Recruiting
Ohio
      University Hospitals of Cleveland, Cleveland,  Ohio,  44106-3878,  United States; Recruiting
South Carolina
      Cannon Park Place, Charleston,  South Carolina,  29187,  United States; Recruiting
Texas
      US Oncology, Mary Crowley Medical Center, Dallas,  Texas,  75246,  United States; Recruiting
      Tyler Cancer Center, Tyler,  Texas,  75702,  United States; Recruiting
      Scott & White Center for Cancer Prevention and Care, Temple,  Texas,  76508,  United States; Recruiting
Virginia
      Medical College of Virginia, Richmond,  Virginia,  23298-0058,  United States; Recruiting

Study ID Numbers:  GV-001.004
Record last reviewed:  October 2004
Record first received:  January 10, 2003
ClinicalTrials.gov Identifier:  NCT00051467
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-11-10