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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT00524186
First received: August 31, 2007
Last updated: January 31, 2014
Last verified: January 2014
  Purpose

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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Sunitinib With FOLFIRI (Irinotecan, 5-Fluorouracil and Leucovorin) for Advanced Gastroesophageal Cancers

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Toxicity [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Response rate as assessed by RECIST criteria [ Time Frame: Every 3 months up to 5 years ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: Every 3 months up to 5 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
  • Circulating endothelial precursor cell (CEC) number [ Time Frame: At baseline ] [ Designated as safety issue: No ]
  • VEGF expression [ Time Frame: At Baseline ] [ Designated as safety issue: No ]
  • Correlation of pre- and post-therapy changes in CEC number and VEGF expression with response rate and survival [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: May 2007
Estimated Study Completion Date: December 2014
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00524186

Locations
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Sponsors and Collaborators
Roswell Park Cancer Institute
Pfizer
Investigators
Principal Investigator: Nikhil Khushalani, MD Roswell Park Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT00524186     History of Changes
Other Study ID Numbers: CDR0000562762, RPCI-I-69605
Study First Received: August 31, 2007
Last Updated: January 31, 2014
Health Authority: United States: Food and Drug Administration

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:
Esophageal Neoplasms
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Stomach Diseases
Fluorouracil
Irinotecan
Sunitinib
Camptothecin
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on April 17, 2014