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

Esophageal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00051480
• Other study ID #: GV-001.005
• Status: Completed
• Phase: Phase 2
• First received: January 10, 2003
• Last updated: May 11, 2011

Study information

• Verified date: May 2011
• Source: GenVec
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Genetic:
• TNFerade

Locations

Country	Name	City	State
United States	Johns Hopkins School of Medicine	Baltimore	Maryland
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	US Oncology, Mary Crowley Center	Dallas	Texas
United States	University of Texas/MD Anderson	Houston	Texas
United States	UCSD Cancer Center	La Jolla	California
United States	University of California, Irvine	Orange	California
United States	Palo Alto VA Health Care Systems	Palo Alto	California
United States	Medical College of Virginia	Richmond	Virginia
United States	St. Louis University	St. Louis	Missouri
United States	Scott & White Center for Cancer Prevention and Care	Temple	Texas
United States	Tyler Cancer Center	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
GenVec

Country where clinical trial is conducted

United States,