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

Gastric Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00524186
• Other study ID #: CDR0000562762
• Secondary ID: RPCI-I-69605
• Status: Terminated
• Phase: Phase 1
• First received: August 31, 2007
• Last updated: June 20, 2016
• Start date: May 2007
• Est. completion date: April 2016

Study information

• Verified date: June 2016
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: April 2016
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 120 Years

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms
• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• fluorouracil
Given IV
• irinotecan hydrochloride
Given IV
• leucovorin calcium
Given IV
• sunitinib malate
Taken Orally

Other:
• flow cytometry
Correlative Study
• pharmacological study
Correlative Study

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York

Sponsors (2)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute	Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of sunitinib malate when administered with FOLFIRI chemotherapy (i.e., irinotecan hydrochloride, fluorouracil, and leucovorin calcium)		30 days after treatment	Yes
Secondary	Toxicity		28 days	Yes
Secondary	Response rate as assessed by RECIST criteria		Every 3 months up to 5 years	No
Secondary	Progression-free survival		Every 3 months up to 5 years	No
Secondary	Overall survival		up to 5 years	No
Secondary	Circulating endothelial precursor cell (CEC) number		At baseline	No
Secondary	VEGF expression		At Baseline	No
Secondary	Correlation of pre- and post-therapy changes in CEC number and VEGF expression with response rate and survival		Every 3 months	No