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

• ClinicalTrials.gov Identifier: NCT00051480
• Recruitment Status: Completed
• First Posted: January 13, 2003
• Last Update Posted: May 12, 2011
• Sponsor: GenVec
• Information provided by: GenVec

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Esophageal Cancer	Genetic: TNFerade	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Primary Purpose: Treatment
• Official Title: A Single Arm, Phase II Study of TNFerade™ Biologic Gene Therapy + Radiation + 5-FU and Cisplatin in Locally Advanced, Resectable, Esophageal Cancer

Arms and Interventions

Outcome Measures

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, California

UCSD Cancer Center

La Jolla, California, United States, 92093-0064

University of California, Irvine

Orange, California, United States, 92868

Palo Alto VA Health Care Systems

Palo Alto, California, United States, 94304

United States, Illinois

The University of Chicago Medical Center

Chicago, Illinois, United States, 60637-1470

United States, Maryland

Johns Hopkins School of Medicine

Baltimore, Maryland, United States, 21231-2410

United States, Missouri

St. Louis University

St. Louis, Missouri, United States, 63110

United States, Ohio

University Hospitals of Cleveland

Cleveland, Ohio, United States, 44106

United States, Texas

US Oncology, Mary Crowley Center

Dallas, Texas, United States, 75246

University of Texas/MD Anderson

Houston, Texas, United States, 77030-4009

Scott & White Center for Cancer Prevention and Care

Temple, Texas, United States, 76508

Tyler Cancer Center

Tyler, Texas, United States, 75702

United States, Virginia

Medical College of Virginia

Richmond, Virginia, United States, 23298-0058

Sponsors and Collaborators

GenVec

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Chang KJ, Reid T, Senzer N, Swisher S, Pinto H, Hanna N, Chak A, Soetikno R. Phase I evaluation of TNFerade biologic plus chemoradiotherapy before esophagectomy for locally advanced resectable esophageal cancer. Gastrointest Endosc. 2012 Jun;75(6):1139-46.e2. doi: 10.1016/j.gie.2012.01.042. Epub 2012 Apr 18.

• Responsible Party: Paul Fischer, PhD, GenVec
• ClinicalTrials.gov Identifier: NCT00051480
• Other Study ID Numbers: GV-001.005
• First Posted: January 13, 2003
• Last Update Posted: May 12, 2011
• Last Verified: May 2011

Additional relevant MeSH terms:

Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases