A Phase I Trial of Imatinib, Bevacizumab, & Metronomic Cyclophosphamide as Antiangiogenic Therapy in Refractory Metastatic Solid Tumors
OBJECTIVES:
Primary
- 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.
Secondary
- 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
transit time).
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.
Interventional
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.
Yes
Emily K. Bergsland, MD
Study Chair
University of California, San Francisco
United States: Institutional Review Board
06991
NCT00390156
August 2006
January 2011
Name | Location |
---|---|
UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco, California 94115 |