Sunitinib, Irinotecan, Fluorouracil, and Leucovorin In Treating Patients With Advanced Stomach Cancer or Gastroesophageal Cancer
Phase I Study of Sunitinib With FOLFIRI (Irinotecan, 5-Fluorouracil and Leucovorin) for Advanced Gastroesophageal Cancers
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.
Studieoversikt
Status
Forhold
Detaljert beskrivelse
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.
Studietype
Registrering (Faktiske)
Fase
- Fase 1
Kontakter og plasseringer
Studiesteder
-
-
New York
-
Buffalo, New York, Forente stater, 14263-0001
- Roswell Park Cancer Institute
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: 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
|
Gitt IV
Gitt IV
Gitt IV
Korrelativ studie
Korrelativ studie
Taken Orally
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Maximum tolerated dose of sunitinib malate when administered with FOLFIRI chemotherapy (i.e., irinotecan hydrochloride, fluorouracil, and leucovorin calcium)
Tidsramme: 30 days after treatment
|
30 days after treatment
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Total overlevelse
Tidsramme: opptil 5 år
|
opptil 5 år
|
|
Toxicity
Tidsramme: 28 days
|
28 days
|
|
Response rate as assessed by RECIST criteria
Tidsramme: Every 3 months up to 5 years
|
Every 3 months up to 5 years
|
|
Progression-free survival
Tidsramme: Every 3 months up to 5 years
|
Every 3 months up to 5 years
|
|
Circulating endothelial precursor cell (CEC) number
Tidsramme: At baseline
|
At baseline
|
|
VEGF expression
Tidsramme: At Baseline
|
At Baseline
|
|
Correlation of pre- and post-therapy changes in CEC number and VEGF expression with response rate and survival
Tidsramme: Every 3 months
|
Every 3 months
|
Samarbeidspartnere og etterforskere
Sponsor
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Patrick Boland, MD, Roswell Park Cancer Institute
Publikasjoner og nyttige lenker
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Sykdommer i fordøyelsessystemet
- Neoplasmer
- Neoplasmer etter nettsted
- Gastrointestinale neoplasmer
- Neoplasmer i fordøyelsessystemet
- Gastrointestinale sykdommer
- Magesykdommer
- Neoplasmer i hode og nakke
- Esophageal sykdommer
- Neoplasmer i magen
- Neoplasmer i spiserøret
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Enzymhemmere
- Antimetabolitter, antineoplastisk
- Antimetabolitter
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Beskyttende agenter
- Topoisomerasehemmere
- Angiogenese-hemmere
- Angiogenesemodulerende midler
- Vekststoffer
- Veksthemmere
- Mikronæringsstoffer
- Proteinkinasehemmere
- Vitaminer
- Kalsiumregulerende hormoner og midler
- Topoisomerase I-hemmere
- Motgift
- Vitamin B kompleks
- Fluorouracil
- Sunitinib
- Leucovorin
- Irinotekan
- Kalsium
- Levoleucovorin
Andre studie-ID-numre
- CDR0000562762
- RPCI-I-69605
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