A Phase I Trial of Imatinib, Bevacizumab, & Metronomic Cyclophosphamide as Antiangiogenic Therapy in Refractory Metastatic Solid Tumors
- Determine the maximum tolerated dose of imatinib when given together with bevacizumab
and metronomic cyclophosphamide in patients with refractory metastatic solid tumors.
- Determine the safety profile of this regimen in these patients.
- Determine the effects of cyclophosphamide and bevacizumab on imatinib pharmacokinetics.
- Determine if patients treated with this regimen achieve plasma levels of
cyclophosphamide that are predicted to be antiangiogenic.
- Determine the effects of this regimen on the number of circulating endothelial cells,
endothelial progenitor cells, activated endothelial cells, and circulating tumor cells.
- Determine the effects of this regimen on parameters measured by CT scan perfusion
(e.g., regional blood flow, blood volume, permeability-surface area product, and mean
OUTLINE: This is a nonrandomized, open-label, pilot, dose-escalation study of imatinib.
Patients receive oral cyclophosphamide and oral imatinib once daily on days 1-28 and
bevacizumab IV on days 1 and 15. Treatment repeats every 28 days in the absence of disease
progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of imatinib 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. At least 6 patients are treated at the MTD.
PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of imatinib when given together with bevacizumab and metronomic cyclophosphamide
Safety data will be assessed after 3 patients and 6 patients complete 42 days of study treatment to determine whether to dose escalate to the next cohort.
Emily K. Bergsland, MD
University of California, San Francisco
United States: Institutional Review Board
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|