E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Renal Cell Cancer, GIST, pancreatic neuroendocrine tumor |
Niercelcarcinoom, GIST, p-NET |
|
E.1.1.1 | Medical condition in easily understood language |
Renal Cell Cancer, GIST, pancreatic neuroendocrine tumor |
Niercelkanker, GIST, p-NET |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067518 |
E.1.2 | Term | Pancreatic neuroendocrine tumor |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023400 |
E.1.2 | Term | Kidney cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10055008 |
E.1.2 | Term | Gastric sarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the influence of morning versus evening administration on
the pharmacokinetics of sunitinib and its metabolite |
Bepalen van de invloed van inname in de ochtend versus inname in de
avond op de farmacokinetiek van sunitinib en de metaboliet |
|
E.2.2 | Secondary objectives of the trial |
To investigate whether daily variation in CYP3A4 activity exists in humans, based on midazolam and 4beta-hydroxycholesterol PK.
To investigate if evening dosing of sunitinib affects the side effects of this drug.
To investigate the influence of single-nucleotide polymorphisms in PK genes on the exposure to sunitinib (based on the MEC02.1002 protocol).
|
Bepalen of er een dagelijke variatie bestaat in expressie van CYP3A4 door middel van midazolam en 4betahydroxycholesterol PK
Bepalen van verschillen in bijwerkingen van sunitinib tussen inname 's ochtends en 's avonds
Bepalen van het effect van SNP in PK gerelateerde genen op de blootstelling aan sunitinib |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age ≥ 18 years;
Histological or cytological confirmed diagnosis of advanced clear-cell renal cell carcinoma, GIST or pancreatic neuro-endocrine tumor, treated with sunitinib;
WHO performance score ≤ 1 at study entry (see appendix A);
Any stable dose of sunitinib at study entry, defined as no dose change within 3 weeks prior to pharmacokinetics;
Adequate hematological functions (ANC > 1.0 x 109/L, platelets > 100 x 1012/L);
Adequate liver and renal function defined as bilirubin concentration ≤ 2 x ULN, AST and ALT ≤ 2.5 x ULN, serum creatinin concentration ≤ 2 x ULN;
Written informed consent;
For patients with reproductive potential a reliable method of contraception (excluding oral contraceptives) must be used
|
Leeftijd boven 18 jaar
Histologisch bewezen gevorderd heldercellig niercelcarcinoom, GIST of p-NET
WHO 1 of lager bij studie inclusie
Stabiele dosis sunitinib bij start studie
Adequate hematologische functie
Adequate nier- en leverfunctie
Getekend informed consent
Adequate anticonceptie |
|
E.4 | Principal exclusion criteria |
Pregnant or child nursing patients;
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;
Major surgery within 2 weeks prior to start of the protocol;
Use of CYP3A4 inhibiting or inducing medication as listed in appendix C;
Patients who are unable to collect blood from;
Patients with known allergy to sunitinib or midazolam;
Patients unwilling or unable to give written informed consent
|
Zwangere vrouwen en vrouwen die borstvoeding geven
Ernstige ziekte of onstabiele medische conditie, symptomatische CNS metastasen, of psychiatrische aandoeningen welke het begrip en geven van informed consent kunnen beinvloeden
Grote operaties binnen 2 weken voorafgaand aan studie
Gebruik van CYP3A4 inhibitoren/inductoren
Patienten waarbij het onmogelijk ik bloedafnames te verrichten
Patienten met een bekende allergie voor sunitinib en/of midazolam
Patienten die geen getekend informed consent kunnen of willen geven |
|
E.5 End points |
E.5.1 | Primary end point(s) |
-Determine differences in sunitinib pharmacokinetics during sunitinib administration in the morning compared to administration in the
evening. |
-Bepalen van verschillen in sunitinib farmacokinetiek tijdens inname in
de ochtend vergeleken met inname in de avond |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Determine differences in adverse effects during sunitinib administration in the morning compared to administration in the
evening. |
Bepalen van verschillen in sunitinib bijwerkingen tijdens inname in de
ochtend vergeleken met inname in de avond. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
18 patients will be included and analysis will be performed on 18
patients |
18 patienten zullen geincludeerd en geanalyseerd worden |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |