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

Roswell Park Comprehensive Cancer Center

Status and phase: Terminated; Phase 1

Conditions: Gastric Cancer; Esophageal Cancer

Treatments: Other: pharmacological study; Drug: sunitinib malate; Drug: fluorouracil; Other: flow cytometry; Drug: irinotecan hydrochloride; Drug: leucovorin calcium

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00524186

CDR0000562762

RPCI-I-69605

Details and patient eligibility

About

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.

Full 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.

Enrollment: 23 patients

Sex: All

Ages: Under 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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23 participants in 1 patient group

Oral Sunitinib

Experimental group

Description:

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

Treatment:

Drug: fluorouracil

Other: pharmacological study

Drug: sunitinib malate

Other: flow cytometry

Drug: leucovorin calcium

Drug: irinotecan hydrochloride