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

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

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.

Study Overview

• Status: Completed
• Conditions: Esophageal Cancer
• Intervention / Treatment: Genetic: TNFerade

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093-0064
      • UCSD Cancer Center
    • Orange, California, United States, 92868
      • University of California, Irvine
    • Palo Alto, California, United States, 94304
      • Palo Alto VA Health Care Systems
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • The University of Chicago Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Johns Hopkins School of Medicine
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • St. Louis University
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland
  • Texas
    • Dallas, Texas, United States, 75246
      • US Oncology, Mary Crowley Center
    • Houston, Texas, United States, 77030-4009
      • University of Texas/MD Anderson
    • Temple, Texas, United States, 76508
      • Scott & White Center for Cancer Prevention and Care
    • Tyler, Texas, United States, 75702
      • Tyler Cancer Center
  • Virginia
    • Richmond, Virginia, United States, 23298-0058
      • Medical College of Virginia

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: GenVec

Publications and helpful links

General Publications

• 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.

Study record dates

Study Registration Dates

• First Submitted: January 10, 2003
• First Submitted That Met QC Criteria: January 10, 2003
• First Posted (Estimate): January 13, 2003

Study Record Updates

• Last Update Posted (Estimate): May 12, 2011
• Last Update Submitted That Met QC Criteria: May 11, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms
• Other Study ID Numbers: GV-001.005