Sunitinib, Irinotecan, Fluorouracil, and Leucovorin In Treating Patients With Advanced Stomach Cancer or Gastroesophageal Cancer
RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan, fluorouracil, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sunitinib together with combination chemotherapy may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of sunitinib when given together with irinotecan, fluorouracil, and leucovorin in treating patients with advanced stomach cancer or gastroesophageal cancer.
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Drug: sunitinib malate
Other: flow cytometry
Other: pharmacological study
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Sunitinib With FOLFIRI (Irinotecan, 5-Fluorouracil and Leucovorin) for Advanced Gastroesophageal Cancers|
- Maximum tolerated dose of sunitinib malate when administered with FOLFIRI chemotherapy (i.e., irinotecan hydrochloride, fluorouracil, and leucovorin calcium) [ Time Frame: 30 days after treatment ] [ Designated as safety issue: Yes ]
- Toxicity [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
- Response rate as assessed by RECIST criteria [ Time Frame: Every 3 months up to 5 years ] [ Designated as safety issue: No ]
- Progression-free survival [ Time Frame: Every 3 months up to 5 years ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
- Circulating endothelial precursor cell (CEC) number [ Time Frame: At baseline ] [ Designated as safety issue: No ]
- VEGF expression [ Time Frame: At Baseline ] [ Designated as safety issue: No ]
- Correlation of pre- and post-therapy changes in CEC number and VEGF expression with response rate and survival [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
|Study Start Date:||May 2007|
|Estimated Study Completion Date:||December 2015|
|Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
Experimental: Oral Sunitinib
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
Given IVDrug: irinotecan hydrochloride
Given IVDrug: leucovorin calcium
Given IVDrug: sunitinib malate
Taken OrallyOther: flow cytometry
Correlative StudyOther: pharmacological study
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00524186
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263-0001|
|Principal Investigator:||Nikhil Khushalani, MD||Roswell Park Cancer Institute|