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

NCT ID: NCT00524186

Last Updated: 2016-06-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2016-04-30

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.

Conditions

Esophageal Cancer; Gastric Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

fluorouracil

Intervention Type: DRUG

Given IV

irinotecan hydrochloride

Intervention Type: DRUG

Given IV

leucovorin calcium

Intervention Type: DRUG

Given IV

sunitinib malate

Intervention Type: DRUG

Taken Orally

flow cytometry

Intervention Type: OTHER

Correlative Study

pharmacological study

Intervention Type: OTHER

Correlative Study

Interventions

fluorouracil

Given IV

Intervention Type: DRUG

irinotecan hydrochloride

Given IV

Intervention Type: DRUG

leucovorin calcium

Given IV

Intervention Type: DRUG

sunitinib malate

Taken Orally

Intervention Type: DRUG

flow cytometry

Correlative Study

Intervention Type: OTHER

pharmacological study

Correlative Study

Intervention Type: OTHER

Eligibility Criteria

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

• 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

• No prior chemotherapy for metastatic disease
• Concurrent therapeutic anticoagulation allowed

Exclusion Criteria

• Symptomatic, uncontrolled CNS metastases

PATIENT CHARACTERISTICS:

• 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:

• Other concurrent investigational therapy
• Concurrent combination antiretroviral therapy in HIV-positive patients
• Major surgery or radiotherapy within the past 3 weeks

• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Roswell Park Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patrick Boland, MD

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Locations

Roswell Park Cancer Institute

Buffalo, New York, United States

Countries

United States

References

Mukherjee S, Fountzilas C, Boland PM, Gosain R, Attwood K, Tan W, Khushalani N, Iyer R. Phase I Study of Irinotecan/5-Fluorouracil/Leucovorin (FOLFIRI) with Sunitinib for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma. Target Oncol. 2020 Feb;15(1):85-92. doi: 10.1007/s11523-019-00692-y.

Reference Type: DERIVED

PMID: 31802410 (View on PubMed)

Other Identifiers

RPCI-I-69605

Identifier Type: -

Identifier Source: secondary_id

CDR0000562762

Identifier Type: -

Identifier Source: org_study_id