Amendment (5-apr-2013): Dosing-time of sunitinib may alter the pharmacokinetics
ID
Bron
Aandoening
Patients with advanced clear cell renal cell carcinoma, metastatic GIST or advanced p-NET treated with sunitinib
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
Difference in pharmacokinetics of sunitinib in morning intake compared to evening intake.
Achtergrond van het onderzoek
Since metabolism of sunitinib is dependant of different cytochrome P450
enzymes, including CYP3A4, which in cell-lines and rodents show a
circadian rhythm in expression, it is very likely that pharmacokinetics
of sunitinib is time dependant. The activity of CYP3A4 probably drops in
night time. Higher concentrations of sunitinib and its active metabolite
may be reached when sunitinib is taken in the evening.
Patients participating in this cross-over study will be followed, during
two courses of sunitinib. In one of both courses, they will take
sunitinib at 08.00 AM, and during the other course at 18.00 PM. During
both courses, they will behospiatlized during 24 hours for
pharmacokinetic measurements of sunitinib.
To investigate the circadian rhythm of CYP3A4, patients will be
administered a low dose of midazolam. Pharmacokinetics of midazolam and
1OH-midazolam will be measured. In addition, also the endogenous marker
4beta-hydroxycholesterol will be studied as an extra test to study
CYP3A4 dynamics.
After completing these two courses, patients are free to decide at wich
time they will continue sunitinib intake.
Amendment: Since metabolism of sunitinib is dependant of different cytochrome P450 enzymes, including CYP3A4, which in cell-lines and rodents show a circadian rhythm in expression, it is very likely that pharmacokinetics of sunitinib is time dependant. Exposure to sunitinib may therefore be influenced by dosing-time.
Patients participating in this cross-over study will be followed, during three courses of sunitinib. In one of three courses, they will take sunitinib at 08.00, one course at 18.00, and one course at 13.00 . During all three courses, they will behospiatlized during 24 hours for pharmacokinetic measurements of sunitinib.
To investigate the circadian rhythm of CYP3A4, patients will be administered a low dose of midazolam. Pharmacokinetics of midazolam and 1OH-midazolam will be measured. In addition, also the endogenous marker 4beta-hydroxycholesterol will be studied as an extra test to study CYP3A4 dynamics.
After completing these three courses, patients are free to decide at wich time they will continue sunitinib intake.
Doel van het onderzoek
Amendment (5-apr-2013): Dosing-time of sunitinib may alter the pharmacokinetics
Onderzoeksopzet
2 courses of sunitinib treatment.
Onderzoeksproduct en/of interventie
1. Blood withdrawal for pharmacokinetics of sunitinib and midazolam;
2. Administration of midazolam;
3. Urine sample collection.
Publiek
Ron H.J. Mathijssen
Groene Hilledijk 301
Rotterdam 3075 EA
The Netherlands
+31 (0)10 7041338, buzzer 229
a.mathijssen@erasmusmc.nl
Wetenschappelijk
Ron H.J. Mathijssen
Groene Hilledijk 301
Rotterdam 3075 EA
The Netherlands
+31 (0)10 7041338, buzzer 229
a.mathijssen@erasmusmc.nl
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
1. Age ¡Ý 18 years;
2. Histological or cytological confirmed diagnosis of advanced clear©\cell renal cell
carcinoma, GIST or pancreatic neuro©\endocrine tumor, treated with sunitinib;
3. WHO performance score ¡Ü 1 at study entry;
4. Any stable dose of sunitinib at study entry, defined as no dose change within 3
weeks prior to pharmacokinetics;
5. Adequate hematological functions (ANC > 1.0 x 109/L, platelets > 100 x 109/L);
6. Adequate liver and renal function defined as bilirubin concentration ¡Ü 2 x ULN, AST
and ALT ¡Ü 2.5 x ULN, serum creatinin concentration ¡Ü 2 x ULN;
7. Written informed consent;
8. For patients with reproductive potential a reliable method of contraception
(excluding oral contraceptives) must be used.
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
1. Pregnant or child nursing patients;
2. Serious illness or medical unstable condition requiring treatment, symptomatic CNS
metastasis or history of psychiatric disorder that would prohibit the understanding
and giving of informed consent;
3. Major surgery within 2 weeks prior to start of the protocol;
4. Use of CYP3A4 inhibiting or inducing medication;
5. Patients who are unable to collect blood from;
6. Patients with known allergy to sunitinib or midazolam;
7. Patients unwilling or unable to give written informed consent.
Opzet
Deelname
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In overige registers
| Register | ID |
|---|---|
| NTR-new | NL3378 |
| NTR-old | NTR3526 |
| Ander register | METC ErasmusMC : 12-138 |
| CCMO | NL39931.078.12 |
| OMON | NL-OMON39190 |