A Single Arm, Phase II Study of TNFerade™ Biologic Gene Therapy + Radiation + 5-FU and Cisplatin in Locally Advanced, Resectable, Esophageal Cancer

Inclusion 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.