The primary purpose of this study is to assess the safety and feasibility of giving TNFerade™ with 5-FU, Cisplatin and radiation therapy to patients with locally advanced, esophageal cancer prior to surgical resection. 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 endoscopy or Endoscopic Ultrasound. 5-FU (1000 mg/m2/day) will be delivered via continuous infusion for 96 hours during weeks 1 and 4. Cisplatin (75 mg/m2) will be delivered on Day 1 and Day 29 intravenously. The dose of radiation delivered will be 45 Gy in 1.8 Gy fractions for 5 weeks.

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

Ages Eligible for Study:  18 Years   -   75 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion criteria:

• 18-75 years for age;
• Patients with biopsy proven locally advanced adenocarcinoma or squamous cell carcinoma of the esophagus, stage II, III, who have not received previous treatment and are considered to have resectable carcinoma;
• Informed consent;
• Karnofsky performance status ≥ 70%;
• Life expectancy greater than 6 months.

Exclusion criteria:

• Diagnosis of lymphoma of the esophagus;
• 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 with patients continuously disease-free;
• Previous chemotherapy or radiation for esophageal cancer or previous radiation therapy to the target field;
• T4 disease, metastatic (stage IV) disease or confirmed invasion of the bronchial tree;
• Extension beyond 2 cm into stomach;
• Liver enzymes >2.0 x ULN (ALT, AST, bilirubin, alkaline phosphatase);
• Coagulopathy (INR >1.5, PTT ratio >1.5);
• Renal insufficiency (creatinine >2.0 mg/dL; calculated creatinine clearance <50 ml/min);
• Significant anemia (hematocrit <28% or hemoglobin <9 g/dL) (may have RBC transfusion), or thrombocytopenia (platelet count <100,000/μL)l or leukopenia (WBC <3,000/µL; ANC <1,500 μL);
• Contraindication to endoscopic or EUS-guided delivery including obstructive lesions that can not be dilated to pass endoscope;
• Clinical evidence of active infection of any type, including hepatitis B or C virus;
• Due to the embryotoxic effects of chemotherapy, pregnant or lactating women, or men unable or unwilling to practice contraception are excluded;
• Experimental medications within the last four weeks prior to Day 1;
• Chronic systemic corticosteriod use (orally or parenterally administered);
• Significant concurrent medical or psychiatric illness as defined by the investigator.

California
      Palo Alto VA Health Care Systems, Palo Alto,  California,  94304,  United States; Suspended
      University of California, Irvine, Orange,  California,  92868,  United States; Recruiting
      University of California, Irvine, Orange,  California,  92868,  United States; Recruiting
      UCSD Cancer Center, La Jolla,  California,  92093-0064,  United States; Recruiting
Illinois
      The University of Chicago Medical Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
Maryland
      Johns Hopkins School of Medicine, Baltimore,  Maryland,  21231-2410,  United States; Recruiting
Missouri
      St. Louis University, St. Louis,  Missouri,  63110,  United States; Recruiting
Ohio
      University Hospitals of Cleveland, Cleveland,  Ohio,  44106,  United States; Recruiting
Texas
      US Oncology, Mary Crowley Center, Dallas,  Texas,  75246,  United States; Recruiting
      Tyler Cancer Center, Tyler,  Texas,  75702,  United States; Recruiting
      University of Texas/MD Anderson, Houston,  Texas,  77030-4009,  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-001.005
Record last reviewed:  October 2004
Record first received:  January 10, 2003
ClinicalTrials.gov Identifier:  NCT00051480
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-11-10