Esophageal Cancer
Conditions
Brief summary
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.
Interventions
GENETICTNFerade
Sponsors
GenVec
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Countries
United States
Outcome results
None listed