Predictive Value of Drug Elimination Gene Polymorphisms on Clearance and Dose Adjustment of Sunitinib in Cancer Patients (CLEARSUN)
11 juli 2012 uppdaterad av: Heinz-Josef Klumpen, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Predictive Value of Drug Elimination Gene Polymorphisms on Clearance and Dose Adjustment of Sunitinib (Sutent, SU11248) in Patients With Cancer
Sunitinib is an anticancer drug, but like most drugs, the effect varies from person to person.
This is partly due to a variation in how well each person eradicates the drug from the body.
This can lead to toxicity if the drug is eliminated slowly.
Just as important is inadvertent underdosing in people who eliminate the drug quickly which may lead to a reduced anti-cancer effect.
The investigators group has developed a battery of tests that may measure how an individual clears a drug from their body.
The investigators intend to apply these tests to a group of patients taking sunitinib to see whether any test will help predict the level of sunitinib in the body and also the side effects.
If a test seems to be promising from this study it may be possible to do a simple test on patients before they receive sunitinib so the best dose is chosen.
The tests involve identifying the genes that are involved with drug elimination (CYP3A, ABCB1, ABCG2, OCT1, OATP) as well as directly measuring elimination using marker drugs (midazolam clearance and sestamibi liver clearance).
Studieöversikt
Status
Avslutad
Betingelser
Studietyp
Observationell
Inskrivning (Faktisk)
52
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
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New South Wales
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Westmead, New South Wales, Australien, 2145
- Westmead Hospital
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Amsterdam, Nederländerna, 1105AZ
- Academic Medical Center Amsterdam
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Rotterdam, Nederländerna, 3075EA
- Erasmus Medical Center, Daniel Den Hoed Cancer Center
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Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år och äldre (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Testmetod
Sannolikhetsprov
Studera befolkning
Patients with a malignancy treated with sunitinib
Beskrivning
Inclusion Criteria:
- Age >18
- A malignancy treated with single agent sunitinib
- ECOG 0, 1 or 2 at time of study accruement
- Any stable dose of therapy with sunitinib (defined as no dose change within 3 weeks prior to blood collection for pharmacokinetics)
- Adequate liver and renal function defined as serum bilirubin concentration less than 2 x ULN, AST and ALT less than 2.5 x ULN, serum creatinine concentration less than 2 x ULN
- No known primary liver disease and no other severe or uncontrolled concurrent medical condition within the first 3 months of treatment with sunitinib.
- Patients who have participated on other clinical studies of sunitinib will be suitable for this study.
- Signed informed consent
- Patients must not have Class ¾ cardiac problems as defined by the New York Heart Association criteria or any other severe or uncontrolled concurrent medical disease.
- Patients must not be pregnant or nursing and must be using an effective contraception method
Exclusion Criteria:
- Patients who are unable to sign informed consent
- Patients unable to give blood
- Patients with known midazolam allergies will not be included
- Patients must not be pregnant or nursing and must be using an effective contraception method
- Patients who had a bone-marrow-transplantation prior to sunitinib treatment
- Patients must not be taking routine systemic corticoid therapy
- Patients must not be taking therapeutic warfarin or warfarin derivates doses as anticoagulation at the time of study tests with an at least 2 weeks warfarin free period of time prior. Patients requiring anticoagulation may use low-molecular weight heparin
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
Kohorter och interventioner
Grupp / Kohort |
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Sunitinib
Patients with a malignancy treated with sunitinib
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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To observe the correlation between ABCB1 polymorphisms in Exons 13, 22 and 27 and the clearance of sunitinib at steady state.
Tidsram: 4 weeks
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A blood sample will be drawn on day 1 of any treatment cycle and at steady state of the same cycle (between Day 21 and 28 inclusive)
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4 weeks
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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To determine whether ABCB1 genotype correlates with toxicity-adjusted dose of sunitinib
Tidsram: 3 months
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Toxicity adjustments will be collected within the first 3 months and correlated with the ABCB1 genotypes.
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3 months
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To determine the pharmacokinetics at steady state of the sunitinib treatment.
Tidsram: 4 weeks
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A blood sample will be drawn on day 1 of treatment cycle and at steady state of the same cycle (between Day 21 and 28 inclusive).
The time of the blood collection are at day1 and in the 4th week: pre-drug administration then at 4 hours, 8 hours and 24 hours after drug intake.
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4 weeks
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To examine correlations between ABCB1 genotype and toxicity grade according to CTC criteria.
Tidsram: 3 months
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The toxicity data of the first 3 months of treatment will be collected.
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3 months
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To examine the correlation between genotype haplotype of other drug elimination genes, such as organic anion transporter proteins (OATP) and other biliary efflux proteins such as MRP2, BCRP with sunitinib clearance and toxicity adjusted dose.
Tidsram: 3 months
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Investigations of drugelimination and clearance taken with in the first 4 weeks of the study will be collected as well as the toxicity data and dose adjustments within the first 3 month of treatment.
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3 months
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Correlation of drug elimination phenotype test (sestamibi liver scan and Midazolam clearance) with sunitinib clearance
Tidsram: 4 weeks
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sestamibi liver scan and midazolam clearance test will be performed pre-treatment and at steady state (sometime between day 21-28)of study participation.
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4 weeks
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Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 januari 2009
Primärt slutförande (Faktisk)
1 juni 2011
Avslutad studie (Faktisk)
1 december 2011
Studieregistreringsdatum
Först inskickad
16 mars 2010
Först inskickad som uppfyllde QC-kriterierna
2 april 2010
Första postat (Uppskatta)
5 april 2010
Uppdateringar av studier
Senaste uppdatering publicerad (Uppskatta)
12 juli 2012
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
11 juli 2012
Senast verifierad
1 juli 2012
Mer information
Termer relaterade till denna studie
Nyckelord
Andra studie-ID-nummer
- HGWH0008
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