E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The clinical trial is conducted in patients undergoing FOLFOX, FOLFIRI and FOLFIRINOX chemotherapy. Most of these patients have colorectal or pancreatic cancer. |
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E.1.1.1 | Medical condition in easily understood language |
Patients undergoing FOLFOX, FOLFIRI and FOLFIRINOX chemotherapy. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
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 |
To determine the percentage of the patients that achieve optimal 5-FU exposure within two dose cycles of 5-FU, which is defined by an AUC target of 5-FU between 20 and 30 mg*h/L or dose limiting toxicity. |
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E.2.2 | Secondary objectives of the trial |
-To determine whether limited sampling of 5-FU blood samples is sufficient to safely adjust 5-FU dosing in routine clinical practice. -To develop a population 5-FU PK model for our Amsterdam UMC 5-FU patients using NONMEM statistics. -To investigate the contribution of bolus 5-FU exposure in PK model as compared to the total exposure calculated with the simple formula: average steady state concentration multiplied by the duration of infusion (Css x t). -To determine the frequency and severity of AEs at 5-FU exposure with below, within and above the target window. -To determine the correlation between DPD activity with 5-FU exposure in the first 5-FU dose cycle. -To determine the intra-individual variation in 5-FU AUCs in all six 5-FU cycles. -To investigate the correlation between AEs and the total 5-FU exposure in six dose cycles.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient undergoing FOLFOX, FOLFIRI or FOLFIRINOX treatment. 2. Patient with age ≥ 18. 3. Patient is able and willing to give written informed consent. 4. Patient is able and willing to undergo extra blood sampling for 5-FU analysis.
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E.4 | Principal exclusion criteria |
1. Patients with known substance abuse, psychotic disorders, and/or other diseases expected to interfere with study or the patient’s safety. 2. Inability to undergo additional blood sampling.
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E.5 End points |
E.5.1 | Primary end point(s) |
The percentage of the patients that achieve optimal 5-FU exposure within two dose cycles of 5-FU, which is defined by an AUC target of 5-FU between 20 and 30 mg*h/L or dose limiting toxicity. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary objective will be evaluated near the end of this study. |
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E.5.2 | Secondary end point(s) |
Secondary endpoints of this study are: the minimum number of samples to assess the AUC of 5-FU, AUC contribution of 5-FU bolus infusion in PK model versus simple formula (Css x t), frequency of AEs below, within and above target window, intra-individual variation in 5-FU AUC, correlation DPD activity with 5-FU exposure and toxicity and the correlation between AEs and total 5-FU exposure. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary objectives will be evaluated near the end of this study |
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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 | Yes |
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 | 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.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
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
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The end of the trial is defined when 30 patients are recruited or when the end of March is reached. |
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |