Phase I Study of Combination Therapy With Oral 9-Nitrocamptothecin and Oral Etoposide
OBJECTIVES: I. Determine the maximum tolerated dose, dose limiting toxicity, and safety of
nitrocamptothecin when administered with etoposide in patients with advanced solid tumors.
II. Determine the changes in expression and activity of topoisomerase I and II which occur
during administration of this treatment regimen in these patients. III. Determine the plasma
pharmacokinetics of this treatment regimen in these patients. IV. Compare the hematologic
and nonhematologic toxicities with this treatment regimen in patients 70 years of age and
older versus patients younger than 70 years of age.
OUTLINE: This is a dose escalation study of nitrocamptothecin. Patients receive oral
nitrocamptothecin on days 1-3 and oral etoposide on days 4-5 each week. Treatment continues
in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients
receive escalating doses of nitrocamptothecin until the maximum tolerated dose (MTD) is
determined. The MTD is defined as the dose preceding that at which 2 of 6 patients
experience dose limiting toxicities. Patients are followed every 4 weeks until toxicities
PROJECTED ACCRUAL: Approximately 40-60 patients will be accrued for this study over 18 to 24
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD)
Determine the MTD of nitrocamptothecin. Cohorts of 3-6 patients receive escalating doses of nitrocamptothecin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities.
Daniel M. Sullivan, M.D.
H. Lee Moffitt Cancer Center and Research Institute
United States: Food and Drug Administration
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|