Sunitinib, Irinotecan, Fluorouracil, and Leucovorin In Treating Patients With Advanced Stomach Cancer or Gastroesophageal Cancer
| Status: | Terminated |
|---|---|
| Conditions: | Cancer, Gastrointestinal |
| Therapuetic Areas: | Gastroenterology, Oncology |
| Healthy: | No |
| Age Range: | Any - 120 |
| Updated: | 6/22/2016 |
| Start Date: | May 2007 |
| End Date: | April 2016 |
Phase I Study of Sunitinib With FOLFIRI (Irinotecan, 5-Fluorouracil and Leucovorin) for Advanced Gastroesophageal Cancers
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.
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.
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.
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.
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
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