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
      University of California, Irvine, Orange,  California,  92868,  United States
      University of California, Irvine, Orange,  California,  92868,  United States
      UCSD Cancer Center, La Jolla,  California,  92093-0064,  United States
Illinois
      The University of Chicago Medical Center, Chicago,  Illinois,  60637-1470,  United States
Maryland
      Johns Hopkins School of Medicine, Baltimore,  Maryland,  21231-2410,  United States
Missouri
      St. Louis University, St. Louis,  Missouri,  63110,  United States
Ohio
      University Hospitals of Cleveland, Cleveland,  Ohio,  44106,  United States
Texas
      US Oncology, Mary Crowley Center, Dallas,  Texas,  75246,  United States
      Tyler Cancer Center, Tyler,  Texas,  75702,  United States
      University of Texas/MD Anderson, Houston,  Texas,  77030-4009,  United States
      Scott & White Center for Cancer Prevention and Care, Temple,  Texas,  76508,  United States
Virginia
      Medical College of Virginia, Richmond,  Virginia,  23298-0058,  United States

Study ID Numbers:  GV-001.005
Record last reviewed:  December 2004
Last Updated:  December 21, 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 2005-04-08