Phase I, Initial Safety/Toxicity Study on the Transfer of Adenovirus With the CD40 Ligand Gene (AdCUCD40L) to Patients With Stage III or IV Esophageal Carcinoma
Esophageal cancer is a deadly disease, with only slow advances in therapy over several
decades, despite a rapid increase in incidence. Esophageal cancer is estimated to be the
seventh most common malignancy worldwide, with incidence rates reaching epidemic proportions
in select regions in Asia and Africa. In the United States, it is estimated that 12,300 new
cases were diagnosed in 2000, however, the incidence of adenocarcinoma of the esophagus is
currently rising faster than that of any other human malignant tumor in this country.
Despite advances in surgical technique, chemotherapy, radiotherapy and early detection, only
12% of patients diagnosed with esophageal cancer will survive more than five years, a cure
rate more dismal than that seen with cancers of the breast, prostate, colon, and even lung.
Survival following treatment for esophageal cancer is stage dependent. This study is
directed towards augmenting host anti-tumor immunity by using gene transfer to activate
dendritic cells (DC; cells of our immune system that play a central role in initiating
immune responses) in tumors of patients with esophageal cancer. Based on extensive
pre-clinical data, two proposed clinical trial protocols will evaluate the concept that
transient modification of the genetic repertoire of esophageal tumors to express CD40 Ligand
(CD40L; a potent activator of DC) will induce the accumulation of activated DC within the
tumor, and the in vivo interaction of DC with the tumor cells/tumor antigens will induce
tumor-specific immunity. To assess this concept, an adenovirus (Ad) vector (AdcuCD40L) will
be used to transfer and transiently express the human CD40L cDNA in esophageal carcinoma by
direct injection into the tumor. Phase I represents a dose escalation study to determine the
maximum tolerated dose of the vector and will include 12 individuals with unresectable,
stage III or IV esophageal cancer. Phase II is a randomized, double-blinded assessment of
biologic efficacy and will include 24 individuals with resectable, stage I-III disease who
will be undergoing potentially curative resection. Together, both protocols are designed to
assess two hypotheses. First, that it is safe to administer the AdcuCD40L vector to
individuals with esophageal cancer. Second, that intratumoral administration of the
AdCUCD40L vector will induce both the accumulation, in the tumor and in regional lymph
nodes, of activated DC, and CD8+ T cells (and other inflammatory cells), including T cells
exhibiting tumor-specific responses, as well as systemic antitumor immunity.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Since this is a dose escalation, phase I design to evaluate toxicity, the analysis for this section will be purely descriptive. Adverse events will be considered on an individual basis.
8 months
Yes
Ronald G Crystal, MD
Principal Investigator
Weill Medical College of Cornell University
United States: Food and Drug Administration
0011004683
NCT00328887
July 2011
June 2029
Name | Location |
---|---|
Weill Medical College of Cornell University | New York, New York 10021 |
The Valley Hospital | Paramus, New Jersey 07652 |