Conditions: Recurrent Melanoma Stage III Melanoma Stage IV Melanoma Unspecified Adult Solid Tumor, Protocol Specific
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 40
Healthy volunteers: no

Brief summary:
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

Detailed description:
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.

Arms:
arm 1: 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.

Interventions: intervention 1: imatinib mesylate intervention 2: bevacizumab intervention 3: pharmacological study intervention 4: laboratory biomarker analysis
Intervention descriptions: intervention 1: Given orally intervention 2: Given IV intervention 3: Correlative studies intervention 4: Correlative studies

Protocol document: