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

Phase 1

Terminated

• Conditions: Gastric Cancer; Esophageal Cancer
• Interventions: Drug: fluorouracil; Drug: irinotecan hydrochloride; Drug: leucovorin calcium; Drug: sunitinib malate; Other: flow cytometry; Other: pharmacological study

• Registration Number: NCT00524186
• Lead Sponsor: 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.

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.

Study Timeline

• Study Start: 2007-05
• Study First Submitted: 2007-08-31
• Study First Submitted QC: 2007-08-31
• Study First Posted: 2007-09-03
• Primary Completion: 2013-08
• Study Completion: 2016-04
• Status Verified: 2016-06
• Last Update Submitted: 2016-06-20
• Last Update Posted: 2016-06-21

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Oral Sunitinib	pharmacological study	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
Oral Sunitinib	leucovorin calcium	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
Oral Sunitinib	flow cytometry	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
Oral Sunitinib	fluorouracil	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
Oral Sunitinib	irinotecan hydrochloride	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
Oral Sunitinib	sunitinib malate	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

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose of sunitinib malate when administered with FOLFIRI chemotherapy (i.e., irinotecan hydrochloride, fluorouracil, and leucovorin calcium)	30 days after treatment

Secondary Outcome Measures

Name	Time	Method
Overall survival	up to 5 years
VEGF expression	At Baseline
Toxicity	28 days
Response rate as assessed by RECIST criteria	Every 3 months up to 5 years
Progression-free survival	Every 3 months up to 5 years
Circulating endothelial precursor cell (CEC) number	At baseline
Correlation of pre- and post-therapy changes in CEC number and VEGF expression with response rate and survival	Every 3 months

Trial Locations

Locations (1)

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States