Trial Information

Phase I Study of Sunitinib With FOLFIRI (Irinotecan, 5-Fluorouracil and Leucovorin) for Advanced Gastroesophageal Cancers

OBJECTIVES:

Primary

- Determine the maximum tolerated dose of sunitinib malate when administered with FOLFIRI
chemotherapy comprising irinotecan hydrochloride, fluorouracil, and leucovorin calcium
in patients with advanced gastroesophageal cancer.

Secondary

- Determine the response rates, overall survival, and progression-free survival of
patients treated with this regimen.

- Determine if there is a change in circulating endothelial precursor cell number and
VEGF expression as a result of this therapy and if these changes correlate with
improved response and survival.

- Document any pharmacokinetic interactions between irinotecan hydrochloride and
sunitinib malate.

- Study pharmacokinetics of sunitinib malate on day 14 (steady state) and day 42 (after 6
weeks of continuous dosing).

OUTLINE: Patients receive oral sunitinib malate on day -7 and then once daily on days 2-28
in course 1 and on days 1-28 in all subsequent courses. Patients also receive FOLFIRI
chemotherapy comprising irinotecan hydrochloride IV over 90 minutes, fluorouracil IV
continuously over 46 hours, and leucovorin calcium IV over 2 hours beginning on days 1 and
15. Treatment repeats every 4 weeks for up to 12 months in the absence of disease
progression or unacceptable toxicity.

Blood is collected at baseline and periodically during study for pharmacokinetic and
biomarker correlative studies. Samples are analyzed by flow cytometry to assess circulating
endothelial cells and VEGF expression.

After completion of study treatment, patients are followed for 4 weeks.