Sunitinib, Irinotecan, Fluorouracil, and Leucovorin In Treating Patients With Advanced Stomach Cancer or Gastroesophageal Cancer

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Esophageal Cancer, Gastric Cancer

Intervention / Treatment
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* Drug: fluorouracil
* Drug: irinotecan hydrochloride
* Drug: leucovorin calcium
* Drug: sunitinib malate
* Other: flow cytometry
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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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 Exclusion criteria: Uncontrolled infection Uncontrolled serious medical disease Uncontrolled hypertension Coagulopathy or bleeding disorder History of allergic reactions attributed to compounds of similar chemical or biological composition to sunitinib malate or other agents used in study PRIOR CONCURRENT THERAPY: Inclusion criteria: No prior chemotherapy for metastatic disease Concurrent therapeutic anticoagulation allowed Exclusion criteria: Other concurrent investigational therapy Concurrent combination antiretroviral therapy in HIV-positive patients Major surgery or radiotherapy within the past 3 weeks

Ages Eligible for Study
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Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral Sunitinib<br>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 | Drug: fluorouracil<br>* Given IV<br>Drug: irinotecan hydrochloride<br>* Given IV<br>Drug: leucovorin calcium<br>* Given IV<br>Drug: sunitinib malate<br>* Taken Orally<br>Other: flow cytometry<br>* Correlative Study<br>Other: pharmacological study<br>* Correlative Study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  | 28 days | 
| 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 | 
| Circulating endothelial precursor cell (CEC) number |  | At baseline | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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