E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-small cell lung carcinoma |
Niet kleincellig longcarcinoom |
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E.1.1.1 | Medical condition in easily understood language |
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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 main objective is to study to what extent cobicistat is able to boost osimertinib exposure when given concurrently in patients who experience low exposure. |
Het primaire doel is om te onderzoeken in welke mate cobicistat in staat is om de blootstelling aan osimertinib te verhogen wanneer deze gelijktijdig worden toegediend bij patiënten die een lage blootstelling ervaren. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate the safety profile of cobicistat with osimertinib when given concurrently. |
Secundair doel van het onderzoek is om de veiligheid te evalueren van de combinatiebehandeling van cobicistat en osimertinib. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with EGFR-mutated NSCLC receiving standard treatment with osimertinib for at least 2 months, without any signs of disease progression. 2. Stable disease, partial response or complete response on the most-recent tumour- response evaluation. 3. Age ≥ 18 years 4. WHO performance status ≤ 2. 5. Able and willing to give written informed consent. 6. Able and willing to undergo blood sampling for pharmacokinetic analysis. 7. Patients with osimertinib plasma trough concentration below 135 ng/mL. Plasma trough concentration of osimertinib will be determined in another study (METC MUMC: 2018-0800, nWMO).
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E.4 | Principal exclusion criteria |
1. Any concurrent medication that is known to strongly inhibit or induce CYP3A4. Appendix A shows a list of drugs which are known to strongly inhibit or induce CYP3A4. 2. Any concurrent medication that is primarily metabolised by CYP3A4 with a narrow therapeutic window. Those drugs are also included in appendix A. 3. Impairment of gastrointestinal function that may alter the absorption of osimertinib or cobicistat (e.g. ulcerative disease, uncontrolled nausea or vomiting, malabsorption syndrome, small bowel resection). 4. Refusing to refrain from consuming CYP3A influencing products, e.g. grapefruit(juice), St. John's wort. 5. Pregnancy or breast feeding. 6. Child-Pugh score class C, chronic liver disease.
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E.5 End points |
E.5.1 | Primary end point(s) |
Exposure (AUC) to osimertinib. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 1 (only osimetinib treatment) Day 22 (after three weeks of concurrent cobicistat treatment) |
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E.5.2 | Secondary end point(s) |
Maximum observed plasma concentration, safety and tolerability. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Maximum observed plasma concentration: similar to AUC. Safety and tolerability: full study (day 1 - day 22), with patient diary. |
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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 | 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
| 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 study-period ends when the patients had visited the hospital for the second time (day 22 of trial) and the AUC has been evaluated two times. If the combination therapy is well tolerated, the patient can opt to continue with the study medication. No additional study visits will be planned. However the patients will continue to visit the hospital for routine controls. |
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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 | |