E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
non-small cell lung cancer, small cell lung cancer, ovarian cancer |
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E.1.1.1 | Medical condition in easily understood language |
Lungcancer and ovarian cancer |
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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 |
The primary objective of the study is to determine the mean prediction error (MPE) and mean absolute prediction error (MAPE) of the area under the plasma concentration-time curve (AUC) of carboplatin after adjusted dosing for high BMI (BMI ≥ 25 kg/m2), low serum creatinine (serum creatinine < 60µm/L), and maximal renal function (GFR = 125 ml/min). |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are:
- to determine the safety of carboplatin after adjusted dosing for high BMI, low serum creatinine, and maximal renal function
- to determine the relationship between the measured creatinine clearance, as measured by collection of a 24-hour urine sample, and the pharmacokinetics of carboplatin after adjusted dosing for high BMI, low serum creatinine, and maximal renal function
- to determine the correlation between the measured 24-hour urinary creatinine clearance and the calculated clearance using the adjusted Cockcroft-Gault formula (adjusted for high BMI, low serum creatinine and maximal renal function)
- to determine the relationship between serum cystatine C and the pharmacokinetics of carboplatin
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- histologically or cytologically proven advanced NSCLC, SCLC or ovarian cancer
- to be treated with carboplatin with a target AUC of 4, 5 or 6
- age 18 years or older
- WHO performance status 0 – 2
- adequate bone marrow and liver function defined as
o haemoglobin ≥ 6.0 mmol/L
o white blood cell count ≥ 3.0 * 109/L
o absolute neutrophil count (ANC) ≥ 1.5 * 109/L
o platelets ≥ 100/L
o bilirubin ≤ 1.5 times ULN
o ALAT and ASAT ≤ 2.5 times ULN (in case of liver metastases ≤ 5.0 times ULN).
- estimated life expectancy of at least 12 weeks
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E.4 | Principal exclusion criteria |
Female patients should not be pregnant or breast-feeding. Female patients with childbearing potential should agree to use effective, non-hormonal means of contraception during the study and for a period of at least 6 months following the last administration of study drugs.
- Treatment with carboplatin with a target AUC of <4
- active clinically serious infection
- history of a kidney allograft
- pregnant
- patients not suitable for follow-up
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the mean prediction error and the mean absolute prediction error in obtaining the target AUC of carboplatin using the new dosing algorithm . |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day one of the first adminstration of carboplatin |
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E.5.2 | Secondary end point(s) |
Secondary endpoints are additional pharmacokinetic parameters (including clearance, half life,) of carboplatin using the new dosing algorithm, and safety of treatment defined as treatment-related toxicity, toxicity-related hospitalization and toxicity-related dose adjustments. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
day one of the first administration of carboplatin, and time interval during which the patient is treated with carboplatin |
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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 | Yes |
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 | No |
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 | Yes |
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
| 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 | 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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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 | |
E.8.9.1 | In the Member State concerned days | |