Esophageal Cancer, Gastric Cancer
Conditions
Keywords
stage III gastric cancer, stage IV gastric cancer, adenocarcinoma of the esophagus, stage IV esophageal cancer, recurrent gastric cancer, recurrent esophageal cancer, adenocarcinoma of the stomach
Brief summary
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.
Detailed description
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.
Interventions
DRUGfluorouracil
Given IV
DRUGirinotecan hydrochloride
Given IV
DRUGleucovorin calcium
Given IV
DRUGsunitinib malate
Taken Orally
OTHERflow cytometry
Correlative Study
OTHERpharmacological study
Correlative Study
Sponsors
Pfizer
Roswell Park Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: Inclusion criteria: * Histologically confirmed diagnosis of 1 of the following: * Locally advanced or unresectable gastric cancer * Metastatic gastric adenocarcinoma * Metastatic gastroesophageal junction (GEJ) adenocarcinoma * Esophageal adenocarcinomas with involvement of GEJ allowed
Exclusion criteria
* Symptomatic, uncontrolled CNS metastases PATIENT CHARACTERISTICS: Inclusion criteria: * ECOG performance status 0-1 * Life expectancy \> 12 weeks * WBC ≥ 3,000/μL * Platelet count ≥ 100,000/μL * Creatinine ≤ 1.5 mg/dL * Bilirubin ≤ 1.5 mg/dL * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose of sunitinib malate when administered with FOLFIRI chemotherapy (i.e., irinotecan hydrochloride, fluorouracil, and leucovorin calcium) | 30 days after treatment |
Secondary
| Measure | Time frame |
|---|---|
| Response rate as assessed by RECIST criteria | Every 3 months up to 5 years |
| Progression-free survival | Every 3 months up to 5 years |
| Overall survival | up to 5 years |
| Toxicity | 28 days |
| VEGF expression | At Baseline |
| Correlation of pre- and post-therapy changes in CEC number and VEGF expression with response rate and survival | Every 3 months |
| Circulating endothelial precursor cell (CEC) number | At baseline |
Countries
United States
Outcome results
None listed