E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 |
5-fluorouracil (5-FU) is the drug most commonly used in the treatment of patients with colorectal cancer. Its efficacy and toxicity can also be evaluated and predicted according to individual pharmacogenetic (PG), pharmacokinetic (PK) and dynamic data (PD). Individual PK is estimated according to drug plasma concentrations –Cpl and kinetic parameters of 5-FU, mainly the AUC as the measure of exposure to drugs. Clinical outcome which is evaluated according to PD parameters, is more depedent on pharmacokinetics than on the dose. This study is devoted to kinetally guided therapy with 5-FU. |
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E.2.2 | Secondary objectives of the trial |
a. The final effect of 5-FU is also dependent on PG conditions which determine enzymatic activity of DPD (dihydropyrimidin reductase), TS (thymidylate synthase), and MTHFR (methylfolate reductase). These enzymes undergo genetic polymorphism. There for this study is also interested in the genotype |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Male and female age of 18 to 80 years, inclusive, caucasian race, suffering from colorectal carcinoma Dukes C, indicated to neoadjuvant chemoradiotherapy. 2) Subject is available for the entire Study Period and will provide his written informed consent. 3) Physical examination without significant deviations. 4) Vital signs without significant deviations. 5) All laboratory screening results within the normal range or being assessed as non-significant by the attending physician. 6) Czech citizenship.
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E.4 | Principal exclusion criteria |
1) History of severe allergy or allergic reactions to the study drugs or related drugs. 2) History of serious clinical illness that can impact on the fate of drugs. 3) Serious mental disease or inability to cooperate with clinical team. 4) Sitting blood pressure after a minimum 5-minute rest < 80/40 mmHg and/or heart rate >120 bpm during the screening procedure. 5) Orthostatic hypotension during the screening procedure or in history. 6) Drug, alcohol or solvents abuse.
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E.5 End points |
E.5.1 | Primary end point(s) |
interindividual variability in pharmacokinetics and dynamics (toxicity) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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) | 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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |