Primary Outcome Measures:
- Progression-free survival as measured by Cox Proportional Hazards Model at 6 months [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Overall survival as measured by Cox Proportional Hazards Model [ Designated as safety issue: No ]
- Response probabilities in subset of patients with measurable disease [ Designated as safety issue: No ]
- Frequency and severity of toxicities as measured by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
- Correlation between growth factor/receptor levels, positron-emission tomography imaging, and immunohistochemistry for p16, VEGF, and VEGFR with kinase mutation status and clinical outcomes [ Designated as safety issue: No ]
- Pharmacokinetics of imatinib mesylate [ Designated as safety issue: No ]
OBJECTIVES:
- Compare the progression-free survival of patients with metastatic or unresectable gastrointestinal stromal tumor treated with imatinib mesylate with vs without bevacizumab.
- Compare the response probabilities (in patients with measurable disease) and overall survival rates in patients treated with these regimens.
- Compare the frequency and severity of toxicities associated with these regimens in these patients.
- Correlate soluble vascular endothelial growth factor (VEGF), VEGF-D, VEGF receptor (VEGFR)-1, VEGFR-2, angiopoietin-2, platelet-derived growth factor receptor (PDGFR)-AA and PDGFR-BB levels, positron-emission tomography imaging, and immunohistochemistry for p16, VEGF, and VEGFR with kinase mutation status and clinical outcomes.
- Examine the pharmacokinetics of imatinib mesylate with single nucleotide polymorphisms involving the ABCG2 and CYP3A4 genes, as well as other genes that are reported to influence the absorption, distribution, metabolism, and elimination of imatinib mesylate.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to Zubrod performance status (0 vs 1-3) and disease status (measurable vs non-measurable). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral imatinib mesylate once daily on days 1-21 and bevacizumab IV over 30-90 minutes on day 1.
- Arm II: Patients receive oral imatinib mesylate once daily on days 1-21. In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood is obtained at baseline, periodically during study treatment, and at disease progression. Blood is analyzed for angiogenesis-related soluble factors, kinase genotyping, pharmacokinetics, and pharmacogenomics.
After completion of study treatment, patients are followed periodically for up to 7 years.
PROJECTED ACCRUAL: A total of 572 patients will be accrued for this study.