Phase I Dose Escalation of Gleevec in Combination With PTK787/ZK 222584 (PTK/ZK) Plus Hydroxyurea
- Determine the maximum tolerated dose and dose-limiting toxicity of imatinib mesylate
and vatalanib when administered with hydroxyurea in patients with recurrent or relapsed
grade 3 or 4 malignant glioma.
- Determine the safety and tolerability of this regimen in these patients.
- Determine the single-dose and repeated-dose pharmacokinetic profiles of imatinib
mesylate (in serum) and vatalanib in these patients.
- Determine the pre- and post-treatment antiangiogenic effects of this regimen in these
patients, using dynamic contrast-enhanced MRI to evaluate changes in the extent of
vascular permeability, perfusion, and relative tumor blood volume.
- Determine whether changes in diffusion-weighted images MRI (quantitated by apparent
diffusion coefficient maps) correlate with tumor cellularity and tumor cell death in
patients treated with this regimen.
- Determine antitumor activity of this regimen, in terms of radiographic response,
progression-free survival, and overall survival, in these patients.
OUTLINE: This is an open-label, dose-escalation study of imatinib mesylate and vatalanib.
Patients receive oral vatalanib once daily, oral imatinib mesylate once daily, and oral
hydroxyurea twice daily on days 1-28*. Treatment repeats every 28 days in the absence of
disease progression or unacceptable toxicity.
NOTE: *Patients receive vatalanib alone daily on days 1-7 followed by vatalanib, imatinib
mesylate, and hydroxyurea on days 8-35 in course 1 only.
Cohorts of 3-6 patients receive escalating doses of imatinib mesylate and vatalanib 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. At least 6
patients are treated at the MTD.
After completion of study treatment, patients will be evaluated for 28 days.
PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose and dose-limiting toxicity of imatinib mesylate and vatalanib when administered with hydroxyurea
David A. Reardon, MD
Duke Cancer Institute
United States: Federal Government
|Duke Comprehensive Cancer Center||Durham, North Carolina 27710|