Imatinib Mesylate and Bevacizumab in Treating Patients With Advanced Melanoma or Other Advanced Cancers
Stage III Melanoma
Stage IV Melanoma
Unspecified Adult Solid Tumor, Protocol Specific
Drug: imatinib mesylate
Other: pharmacological study
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study Of Imatinib Mesylate And Bevacizumab In Patients With Advanced Melanoma And Other Advanced Cancers|
- 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) [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
- Progression-free survival at 8 weeks (Phase II) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]We will evaluate the percentage of patients who are progression-free at 8 weeks. Kaplan-Meier estimates of progression free survival and 95% confidence intervals will be calculated.
- Response rate at 8 weeks, evaluated using RECIST (Phase II) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]We will estimate response rates and 95% confidence intervals.
- Overall survival (Phase II) [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]Kaplan-Meier estimates of overall survival and 95% confidence intervals will be calculated.
|Study Start Date:||October 2003|
|Primary Completion Date:||July 2009 (Final data collection date for primary outcome measure)|
Experimental: Arm I
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.
Drug: imatinib mesylate
Other Names:Biological: bevacizumab
Other Names:Other: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
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 cancers.
II. Determine the response rate, time to progression, and survival of patients treated with this regimen.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00074308
|United States, Pennsylvania|
|Abramson Cancer Center of The University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Keith Flaherty||Abramson Cancer Center of the University of Pennsylvania|