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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00524186
Recruitment Status : Terminated (PI left institute)
First Posted : September 3, 2007
Last Update Posted : June 21, 2016
Information provided by (Responsible Party):
Roswell Park Cancer Institute

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.

Condition or disease Intervention/treatment Phase
Esophageal Cancer Gastric Cancer Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium Drug: sunitinib malate Other: flow cytometry Other: pharmacological study Phase 1

Detailed Description:



  • 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Sunitinib With FOLFIRI (Irinotecan, 5-Fluorouracil and Leucovorin) for Advanced Gastroesophageal Cancers
Study Start Date : May 2007
Actual Primary Completion Date : August 2013
Actual Study Completion Date : April 2016

Arm Intervention/treatment
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
Drug: fluorouracil
Given IV

Drug: irinotecan hydrochloride
Given IV

Drug: leucovorin calcium
Given IV

Drug: sunitinib malate
Taken Orally

Other: flow cytometry
Correlative Study

Other: pharmacological study
Correlative Study

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Toxicity [ Time Frame: 28 days ]
  2. Response rate as assessed by RECIST criteria [ Time Frame: Every 3 months up to 5 years ]
  3. Progression-free survival [ Time Frame: Every 3 months up to 5 years ]
  4. Overall survival [ Time Frame: up to 5 years ]
  5. Circulating endothelial precursor cell (CEC) number [ Time Frame: At baseline ]
  6. VEGF expression [ Time Frame: At Baseline ]
  7. Correlation of pre- and post-therapy changes in CEC number and VEGF expression with response rate and survival [ Time Frame: Every 3 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   up to 120 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


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


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


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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00524186

United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Sponsors and Collaborators
Roswell Park Cancer Institute
Principal Investigator: Patrick Boland, MD Roswell Park Cancer Institute

Responsible Party: Roswell Park Cancer Institute Identifier: NCT00524186     History of Changes
Other Study ID Numbers: CDR0000562762
First Posted: September 3, 2007    Key Record Dates
Last Update Posted: June 21, 2016
Last Verified: June 2016

Keywords provided by Roswell Park Cancer Institute:
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

Additional relevant MeSH terms:
Stomach Neoplasms
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances