E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The main group are patients with renal cell cancer currently being or about to be treated with sunitinib. Other diseases with efficacy of sunitinib are Gastro Intestinal Stromal cell tumour (GIST). |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To observe the correlation between ABCB1 polymorphisms in Exons 13, 22 and 27 and the clearance of sunitinib at steady state. |
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E.2.2 | Secondary objectives of the trial |
• To determine whether ABCB1 genotype correlates with toxicity-adjusted dose of sunitinib • To determine the pharmacokinetics at steady state of the sunitinib treatment. • To examine correlations between ABCB1 genotype and toxicity grade according to CTC criteria. • 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. • Correlation of drug elimination phenotype test (sestamibi liver scan and Midazolam clearance) with sunitinib clearance |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The endpoint of the study is a correlation between sunitinib clearance and toxicityadjusted dose with ABCB1 genotype examining SNPs in exons 13, 22,and 27 as well as haplotypes of these exons. |
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | Yes |
E.7.1.3.1 | Other trial type description |
non therapeutic intervention exploratory study of clinical pharmacology and pharmacogenetics |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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.8.5 | 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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |