A Phase I Trial of Intravesical Ad-p53 Treatment in Locally Advanced and Metastatic Bladder Cancer
I. Determine the safety and toxicity of adenovirus p53 (Ad-p53) gene therapy in patients
with locally advanced or metastatic bladder cancer.
II. Measure infection with Ad-p53 and confirm expression of p53 after infection.
III. Characterize clinical response of measurable tumor in these patients. IV. Determine the
duration of effect of this treatment in these patients. V. Define the time course of
elimination of vector from urinary bladder.
OUTLINE: This is a dose escalation study.
Group 1 patients receive adenovirus p53 (Ad-p53) intravesically on days 1 and 4. Treatment
continues every 4 weeks for a maximum of 6 courses in the absence of disease progression or
Cohorts of 3 patients in group 1 receive escalating doses of Ad-p53. In the absence of grade
3 or worse toxicity in the first 3 patients treated, subsequent cohorts of 3 patients each
receive escalating doses of Ad-p53 on the same schedule. If 1 of 3 patients experiences
grade 3 toxicity, an additional 3 patients are treated at that dose level and dose
escalation continues. If 1 of 3 patients experience grade 4 toxicity or 2 of 3 patients
experience grade 3 toxicity, dose escalation ceases and the MTD is defined as the previous
dose level. Group 2 patients receive Ad-p53 at the MTD on days 1-4, and group 3 patients
receive Ad-p53 at the MTD on days 1-4 and 8-11.
Patients are followed on day 28, then every 3 months for 1 year or until disease
PROJECTED ACCRUAL: A maximum of 24 patients will be accrued for this study (3-12 patients
for group 1; 3-6 patients for group 2; and 6 patients for group 3).
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum-tolerated dose as assessed by NCI Common Terminology Criteria (CTC) version 2.0
M.D. Anderson Cancer Center
United States: Food and Drug Administration
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