A Phase I/II Study Of Imatinib Mesylate And Bevacizumab In Patients With Advanced Melanoma And Other Advanced Cancers
I. Determine the tolerability, maximum tolerated dose, and lowest biologically active dose
of imatinib mesylate and bevacizumab in patients with advanced melanoma or other advanced
II. Determine the response rate, time to progression, and survival of patients treated with
III. Correlate clinical activity with inhibition of platelet-derived growth factor receptor
beta, vascular endothelial growth factor receptor, flt-1, and markers of angiogenesis in
patients treated with this regimen.
IV. Correlate clinical activity with alterations in tumor perfusion as assessed by dynamic
contrast-enhanced MRI and Doppler ultrasound in patients treated with this regimen.
V. Correlate toxicity, clinical activity, and correlative endpoints with the steady-stage
plasma concentration of imatinib mesylate in patients treated with this regimen.
OUTLINE: This is a dose-escalation, open-label study.
PHASE I (closed to accrual as of 8/23/04): Patients receive oral imatinib mesylate once or
twice daily on days 1-28 and bevacizumab IV over 30-90 minutes on days 1 and 14. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of imatinib mesylate and bevacizumab 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 imatinib mesylate and bevacizumab as in phase I at the MTD.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD, defined as one dose level below the dose that induced DLT in at least one third of patients at a dose level, graded according to NCI CTCAE version 3.0 (Phase I)
Up to 28 days
Abramson Cancer Center of the University of Pennsylvania
United States: Food and Drug Administration
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