Biomarker-Guided Fluorouracil in Treating Patients With Colorectal Cancer Receiving Combination Chemotherapy
7. oktober 2015 opdateret af: UNC Lineberger Comprehensive Cancer Center
Multicenter Study Investigating Utilization of Pharmacokinetic-Guided 5-Fluorouracil in Patients Receiving mFOLFOX6 With or Without Bevacizumab
RATIONALE: Drugs used in chemotherapy, such as fluorouracil, oxaliplatin, and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug, combination chemotherapy, may kill more tumor cells. Studying samples of blood in the laboratory from patients with cancer receiving fluorouracil in combination with oxaliplatin and leucovorin calcium may help doctors learn how fluorouracil works in the body and how patients will respond to treatment.
PURPOSE: This phase I trial is studying biomarker-guided fluorouracil in treating patients with colorectal cancer receiving combination chemotherapy.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
OBJECTIVES:
Primary
- To determine whether 4 courses of pharmacokinetic (PK)-guided 5-fluorouracil chemotherapy improves the ability to achieve a targeted area under the curve (20 to 25 mg*hr/L) in patients with colorectal cancer receiving mFOLFOX6 chemotherapy as compared to historical non-PK-guided therapy in patients treated with a similar FOLFOX regimen.
Secondary
- To determine and compare the incidence of neutropenia and diarrhea in patients treated with these regimens.
OUTLINE: This is a multicenter study.
- Standard mFOLFOX6 (course 1): Patients receive fluorouracil IV bolus over 1-5 minutes followed by fluorouracil IV continuously over 46 hours, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours on day 1.
Patients undergo plasma sample collection periodically during study for pharmacokinetic (PK)-guided fluorouracil dose determination for courses 2-4.
- PK-guided mFOLFOX6 (courses 2-4): Patients receive fluorouracil bolus, oxaliplatin, and leucovorin calcium as in course 1. Patients also receive fluorouracil* IV continuously as determined by the PK-guided analysis.
NOTE: *The continuous infusion fluorouracil dose adjustment is calculated based on the results of PK plasma concentrations and the corresponding AUC from the preceding course.
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
76
Fase
- Fase 1
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
-
-
North Carolina
-
Asheville, North Carolina, Forenede Stater, 28801
- Cancer Care of Western North Carolina
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Greensboro, North Carolina, Forenede Stater, 27403-1198
- Moses Cone Regional Cancer Center at Wesley Long Community Hospital
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Greenville, North Carolina, Forenede Stater, 27834
- Leo W. Jenkins Cancer Center at ECU Medical School
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Raleigh, North Carolina, Forenede Stater, 27607
- Rex Cancer Center at Rex Hospital
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Washington, North Carolina, Forenede Stater, 27889
- Marion L. Shepard Cancer Center
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-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
- Barn
- Voksen
- Ældre voksen
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
DISEASE CHARACTERISTICS:
- Histologically confirmed colorectal cancer
- Patients scheduled to receive mFOLFOX6 (in the adjuvant setting or for metastatic disease) as part of their chemotherapy regimen
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy > 6 months
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Serum creatinine ≤ 1.5 mg/dL
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver metastases)
- Fertile patients must use effective contraception
- Negative pregnancy test
- Not pregnant or nursing
- No serious concomitant systemic disorders, including active infection that, in the opinion of the investigator, would compromise the patient's safety or ability to complete the study
- No altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies
- Must be able to follow protocol requirements and give informed consent
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Concurrent bevacizumab allowed
No concurrent warfarin (Coumadin®)
- Concurrent enoxaparin (Lovenox®) allowed
- No concurrent theophylline or aminophylline
- No chocolate beginning 12 hours before day 1 of each course and through the end of that course's fluorouracil continuous IV
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: mFOLFOX6
Patients will receive cycle 1 of standard dose mFOLFOX6, with the same dose of mFOLFOX6 continued in subsequent cycles, once patient achieves the target AUC. mFOLFOX 6 is a regimen comprised of Oxaliplatin + Leucovorin +5-Fluorouracil (FU) |
200-400 mg/m2 intravenously, 1 -5 minutes, once every 2 weeks 2400 mg/m2 intravenously over a period of 46 hours, once every 2 weeks
Andre navne:
200-400 mg/m2, intravenously over a period of 2 hours, once every 2 weeks
Andre navne:
85 mg/m2, intravenously for 2 hours, once every 2 weeks
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Achievement of targeted AUC using pharmacokinetic (PK)-guided 5 fluorouracil as part of mFOLFOX6 therapy
Tidsramme: During first 4 cycles of drug therapy
|
During first 4 cycles of drug therapy
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Toxicity differences between PK-guided therapy versus non-PK-guided therapy
Tidsramme: 24 months
|
24 months
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Samarbejdspartnere
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
- Williams GR, Deal AM, Shachar SS, Walko CM, Patel JN, O'Neil B, McLeod HL, Weinberg MS, Choi SK, Muss HB, Sanoff HK. The impact of skeletal muscle on the pharmacokinetics and toxicity of 5-fluorouracil in colorectal cancer. Cancer Chemother Pharmacol. 2018 Feb;81(2):413-417. doi: 10.1007/s00280-017-3487-2. Epub 2017 Nov 20.
- Patel JN, O'Neil BH, Deal AM, Ibrahim JG, Sherrill GB, Olajide OA, Atluri PM, Inzerillo JJ, Chay CH, McLeod HL, Walko CM. A community-based multicenter trial of pharmacokinetically guided 5-fluorouracil dosing for personalized colorectal cancer therapy. Oncologist. 2014 Sep;19(9):959-65. doi: 10.1634/theoncologist.2014-0132. Epub 2014 Aug 12.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. februar 2010
Primær færdiggørelse (Faktiske)
1. november 2012
Studieafslutning (Faktiske)
1. september 2013
Datoer for studieregistrering
Først indsendt
15. juli 2010
Først indsendt, der opfyldte QC-kriterier
15. juli 2010
Først opslået (Skøn)
16. juli 2010
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
9. oktober 2015
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
7. oktober 2015
Sidst verificeret
1. oktober 2015
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Sygdomme i fordøjelsessystemet
- Neoplasmer
- Neoplasmer efter sted
- Hæmatologiske sygdomme
- Tegn og symptomer, fordøjelsessystemet
- Gastrointestinale neoplasmer
- Neoplasmer i fordøjelsessystemet
- Gastrointestinale sygdomme
- Tyktarmssygdomme
- Tarmsygdomme
- Intestinale neoplasmer
- Endetarmssygdomme
- Agranulocytose
- Leukopeni
- Leukocytlidelser
- Kolorektale neoplasmer
- Diarré
- Neutropeni
- Lægemidlers fysiologiske virkninger
- Molekylære mekanismer for farmakologisk virkning
- Antimetabolitter, Antineoplastisk
- Antimetabolitter
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Beskyttelsesagenter
- Mikronæringsstoffer
- Vitaminer
- Modgift
- Vitamin B kompleks
- Fluorouracil
- Oxaliplatin
- Leucovorin
- Levoleucovorin
Andre undersøgelses-id-numre
- LCCC 0918
- P30CA016086 (U.S. NIH-bevilling/kontrakt)
- CDR0000681338 (Anden identifikator: PDQ number)
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .