Effects of morning vs evening dosing on the pharmacokinetics and pharmacodynamics of sunitinib.

Conditions: Renal Cell Cancer, GIST, pancreatic neuroendocrine tumor
MedDRA version: 14.1Level: LLTClassification code 10067518Term: Pancreatic neuroendocrine tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1Level: LLTClassification code 10023400Term: Kidney cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1Level: PTClassification code 10055008Term: Gastric sarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2012-000425-45-NL

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 18

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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the influence of morning versus evening administration on<br>the pharmacokinetics of sunitinib and its metabolite;Secondary Objective: To investigate whether daily variation in CYP3A4 activity exists in humans, based on midazolam and 4beta-hydroxycholesterol PK.<br>To investigate if evening dosing of sunitinib affects the side effects of this drug.<br>To investigate the influence of single-nucleotide polymorphisms in PK genes on the exposure to sunitinib (based on the MEC02.1002 protocol).<br>;Primary end point(s): -Determine differences in sunitinib pharmacokinetics during sunitinib administration in the morning compared to administration in the<br>evening.;Timepoint(s) of evaluation of this end point: 1 year

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Determine differences in adverse effects during sunitinib administration in the morning compared to administration in the<br>evening.;Timepoint(s) of evaluation of this end point: 1 year