Study of TNFerade™ Gene Therapy, Radiation, 5-FU and Cisplatin in Esophageal Cancer

Study Overview
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Brief Summary
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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.

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

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Genetic: TNFerade


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Genetic: TNFerade|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |