Phase II trial to study the effectiveness of combining imatinib mesylate with bevacizumab in treating patients who have advanced melanoma or other metastatic or unresectable cancer. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Bevacizumab may stop the growth of tumor cells by stopping blood flow to the tumor. Combining imatinib mesylate with bevacizumab may kill more tumor cells
OBJECTIVES: 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Abramson Cancer Center of The University of Pennsylvania
Philadelphia, Pennsylvania, United States
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
Progression-free Survival at 16 Weeks (Phase II)
Progression Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: 16 weeks
Response Rate at 8 Weeks, Evaluated Using RECIST (Phase II)
Response and progression was evaluated in this study using Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Time frame: 8 weeks
Overall Survival (Phase II)
Kaplan-Meier estimates of overall survival and 95% confidence intervals will be calculated.
Time frame: Up to 6 years
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