Clinical Protocol for Wild Type p53 Gene Induction in Premalignancies of Squamous Epithelium of the Oral Cavity and Oral Pharynx Via an Adenoviral Vector [NCI Supplied Agent Ad-p53, (INGN 201) (Advexin®) NSC 683550, IND# 7135]
I. Determine the acute toxic effects of Ad5CMV-p53 gene administered as an oral rinse and as
an intramucosal injection in patients with diffuse premalignant carcinoma of the oral cavity
or oral pharynx.
II. Determine the maximum tolerated dose of this drug in these patients. III. Determine the
topical transduction efficiency of adenoviral-mediated wild type p53 gene transfer in
patients treated with this drug.
IV. Determine the efficacy of this drug in reversing the histology of oral premalignancies
in these patients.
V. Determine the distribution of transgenic protein within the area of the premalignant
lesion in patients treated with this drug.
OUTLINE: This is an open-label, dose-escalation study of Ad5CMV-p53 gene administered as an
Phase I: Patients receive Ad5CMV-p53 gene by intramucosal injection into the area of the
lesion followed at least 2 hours later by Ad5CMV-p53 gene as an oral rinse on day 1.
Patients then receive Ad5CMV-p53 gene as an oral rinse twice daily on days 2-5. Treatment
repeats every 28 days for 6 courses in the absence of disease progression or unacceptable
toxicity. Cohorts of 3-6 patients receive escalating doses of Ad5CMV-p53 gene as an oral
rinse until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Phase II: Patients receive treatment with intramucosal Ad5CMV-p53 gene as in phase I and
Ad5CMV-p53 gene as an oral rinse at the MTD. Patients are followed every 3 months for 1
year, every 6 months for 1 year, and then annually for 3 years. Patients then receive
long-term follow-up annually for an additional 10 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
Frequency of adverse events
Up to 15 years
Gary L. Clayman
M.D. Anderson Cancer Center
United States: Food and Drug Administration
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