Phase I/II Study of SU11248 (Sutent) in Combination With Metronomic Dosing of Cyclophosphamide and Methotrexate in Patients With Metastatic Breast Cancer
- To determine the maximum tolerated dose of the combination of metronomic dose
cyclophosphamide and methotrexate with continuous dosing sunitinib malate. (Phase I)
- To determine the time to disease progression in patients with metastatic breast cancer
treated with metronomic dose chemotherapy with cyclophosphamide and methotrexate
combined with continuous dosing of sunitinib malate. (Phase II)
- To determine the response rate in patients receiving this treatment.
- To determine the duration of response in patients receiving this treatment.
- To determine the toxicity of this regimen in these patients.
- To determine the feasibility by assessment of toxicities of this regimen and number of
voluntary withdrawals from the study.
- To correlate outcome measures with possible surrogate markers including serial
measurements of circulating tumor cells and circulating endothelial cells.
OUTLINE: This is a dose-escalation study of sunitinib malate.
- Phase I: Patients receive oral sunitinib malate once daily. Beginning 14 days later,
patients also receive oral cyclophosphamide once daily on days 1-21 and oral
methotrexate twice daily on days 1, 2, 8, 9, 15, and 16. Treatment with sunitinib
malate, cyclophosphamide, and methotrexate repeats every 21 days* in the absence of
disease progression or unacceptable toxicity.
- Phase II: Patients receive sunitinib malate at the maximum tolerated dose determined in
phase I and cyclophosphamide and methotrexate as in phase I.
NOTE: *Course 1 includes 2 weeks of sunitinib malate alone followed by sunitinib malate,
cyclophosphamide, and methotrexate for 21 days
Blood samples are collected periodically for measurement of circulating tumor cells,
circulating endothelial cells, and VEGF levels.
After completion of study treatment, patients are followed for 30 days and then every 2
months for 1 year.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (Phase I)
until disease progression up to 13 months post treatment
Hope S. Rugo, MD
University of California, San Francisco
United States: Food and Drug Administration
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|