Oral ST1481 in Adults With Malignant Glioma: A Phase I-II Clinical Trial
- Determine the maximum tolerated dose (MTD) of gimatecan in patients with recurrent or
progressive primary malignant glioma treated with or without concurrent enzyme-inducing
- Determine whether this drug has sufficient activity to warrant further development in
these patients. (phase II)
- Determine the qualitative and quantitative toxic effects of this drug in these
- Determine the pharmacokinetic behaviors of this drug in these patients.
- Correlate the principal toxic effects with the pertinent pharmacokinetic parameters of
this drug in these patients.
- Determine the antitumor activity of this drug in these patients.
OUTLINE: This is an open-label, dose-escalation, multicenter study. Patients are stratified
according to the concurrent use of enzyme-inducing anticonvulsant drugs (yes vs no).
- Phase I: Patients receive oral gimatecan once daily on days 1-5. Courses repeat every
28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of gimatecan 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 gimatecan as in phase I at the MTD. Patients are followed
for at least 1 month and then every 2 months thereafter.
PROJECTED ACCRUAL: Approximately 30-83 patients (30-42 for phase I [15-21 per stratum] and
21-41 for phase II) will be accrued for this study within 24 months.
Masking: Open Label, Primary Purpose: Treatment
Timothy F. Cloughesy, MD
Jonsson Comprehensive Cancer Center
United States: Federal Government
|Jonsson Comprehensive Cancer Center at UCLA||Los Angeles, California 90095-1781|