Imatinib Mesylate, Vatalanib, and Hydroxyurea in Treating Patients With Recurrent or Relapsed Malignant Glioma
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|ClinicalTrials.gov Identifier: NCT00387933|
Recruitment Status : Completed
First Posted : October 13, 2006
Last Update Posted : October 14, 2015
RATIONALE: Imatinib mesylate, vatalanib, and hydroxyurea may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vatalanib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving imatinib mesylate and vatalanib together with hydroxyurea may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of imatinib mesylate and vatalanib when given together with hydroxyurea in treating patients with recurrent or relapsed malignant glioma.
|Condition or disease||Intervention/treatment||Phase|
|Brain and Central Nervous System Tumors||Drug: hydroxyurea Drug: imatinib mesylate Drug: vatalanib||Phase 1|
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||37 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Dose Escalation of Gleevec in Combination With PTK787/ZK 222584 (PTK/ZK) Plus Hydroxyurea|
|Study Start Date :||July 2005|
|Actual Primary Completion Date :||January 2009|
Experimental: Gleevec + PTK787/ZK 22584 + Hydroxyurea
Patients with recurrent or relapsing glioblastoma multiforme (GBM) will be given daily doses of Gleevec and PTK787/ZK 22584 orally in combination with fixed doses of hydroxyurea.
Drug: imatinib mesylate
Other Name: Gleevec
Other Name: PTK787
- Maximum tolerated dose and dose-limiting toxicity of imatinib mesylate and vatalanib when administered with hydroxyurea [ Time Frame: 1 Year ]
- Safety [ Time Frame: 1.5 Years ]
- Tolerability [ Time Frame: 1 Year ]
- Pharmacokinetic [ Time Frame: 1.5 Years ]To characterize the single-dose and repeated-dose pharmacokinetic (PK) profiles of imatinib mesylate (in serum) and PTK787/ZK 22584 combination therapy in this patient population.
- Antiangiogenic effects [ Time Frame: 1 Year ]
pre- and post-treatment, of imatinib mesylate, PTK787/ZK 22584 and hydroxyurea combination therapy, using Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) to evaluate changes in the extent of vascular permeability, perfusion and relative tumor blood volume; to explore assessment of tumor cellularity and tumor cell death by changes in diffusion weighted imaging magnetic resonance imaging (DWI-MRI) as quantitated by apparent diffusion coefficient maps (ADC maps).
To note the anti-tumor activity of this regimen in terms of radiographic response, progression-free survival and overall survival.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00387933
|United States, North Carolina|
|Duke Comprehensive Cancer Center|
|Durham, North Carolina, United States, 27710|
|Study Chair:||David A. Reardon, MD||Duke Cancer Institute|