Clinical trial NCT00524186: Sunitinib, Irinotecan, Fluorouracil, and Leucovorin In Treating Patients With Advanced Stomach Cancer or Gastroesophageal Cancer
Official title: Phase I Study of Sunitinib With FOLFIRI (Irinotecan, 5-Fluorouracil and Leucovorin) for Advanced Gastroesophageal Cancers
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Esophageal Cancer
Gastric Cancer
Keywords: 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
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2007-09-03
Enrollment: 23
Sex: ALL
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Maximum tolerated dose of sunitinib malate when administered with FOLFIRI chemotherapy (i.e., irinotecan hydrochloride, fluorouracil, and leucovorin calcium)
timeFrame: 30 days after treatment
Secondary outcomes:
measure: Toxicity
timeFrame: 28 days
measure: Response rate as assessed by RECIST criteria
timeFrame: Every 3 months up to 5 years
measure: Progression-free survival
timeFrame: Every 3 months up to 5 years
measure: Overall survival
timeFrame: up to 5 years
measure: Circulating endothelial precursor cell (CEC) number
timeFrame: At baseline
measure: VEGF expression
timeFrame: At Baseline
measure: Correlation of pre- and post-therapy changes in CEC number and VEGF expression with response rate and survival
timeFrame: Every 3 months
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: Patrick Boland, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.