E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non small cell lung cancer |
Niet-kleincellig longkanker |
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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 |
To evaluate the area under the curve of afatinib compared to afatinib concomitantly used with esomeprazole and to afatinib used with esomeprazole 3 hours prior in patients with non-small cell lung cancer. |
De biologische beschikbaarheid van afatinib evalueren bij afatinib gelijktijdig ingenomen met esomeprazol vergeleken met afatinib met esomeprazol 3 uur eerder ingenomen, bij patiënten met niet-kleincellig longkanker. |
|
E.2.2 | Secondary objectives of the trial |
1. Other pharmacokinetic outcomes (i.e. clearance, maximum concentration and time to Cmax). 2. To evaluate the incidence and severity of side-effects of treatment with afatinib in absence and presence of esomeprazole.
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1. Andere farmacokinetische uitkomstmaten (bijv. klaring, maximale concentratie, tijd tot Cmax). 2. Evalueren van de incidentie en ernst van bijwerkingen van afatinib met of zonder esomeprazol ingenomen. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 18 years 2. Histological or cytological confirmed diagnosis of EGFR-mutated NSCLC 3. WHO Performance Status ≤ 1 4. Able and willing to sign the Informed Consent Form prior to screening evaluations 5. No concurrent (over the counter) use of other acid reducing drugs (PPIs, H2As and/or antacids), other than esomeprazole 40mg once daily during the study. 6. No concurrent medication or supplements which can interact with esomeprazole or afatinib during the study period (such as PgP-inhibitors/inducers). 7. Abstain from grapefruit, grapefruit juice, herbal dietary supplements, cranberry juice, and herbal tea during the study period. 8. Adequate baseline patient characteristics (complete blood count, and serum biochemistry which involves sodium, calcium, potassium, creatinin, calculation of creatinin clearance (MDRD), AST, ALT, gamma-GT, lactate dehydrogenase (LDH), total bilirubin, albumin, glucose within two weeks prior to the study. |
1. Leeftijd ≥ 18 jaar 2. Histologisch of cytologisch bewezen diagnose van EGFR-gemuteerd niet-kleincellig longcarcinoom 3. WHO Performance Status ≤ 1 4. Patiënt is in staat en bereid om het Informed Consent formulier te tekenen voorafgaand aan de screening 5. Tijdens de studie geen gebruik van andere maagzuurverlagende medicijnen (PPI, H2A's en/of antaciden), behalve esomeprazol 40mg eenmaal daags gedurende de studie 6. Tijdens de studie geen gebruik van medicijnen of supplementen die interactie kunnen geven met esomeprazol of afatinib (zoals PgP-remmers/inducers) 7. Patiënt dient zich tijdens de studie te wilen onthouden van grapefruit (sap), kruidensupplementen, cranberry sap, kruidenthee 8. Adequate baseline patient karakteristieken binnen twee weken voor de studie (bloedbeeld, biochemie met natrium, calcium, kalium, kreatinine, kreatinineklaring (MDRD), ASAT, ALAT, gamma-GT, lactaat dehydrogenase (LDH), totaal bilirubine, albumine, glucose) |
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E.4 | Principal exclusion criteria |
1. Pregnant or lactating patients. 2. Patients with known impaired drug absorption (e.g. gastrectomy and achlorhydria) 3. Known serious illness or medical unstable conditions that could interfere with this study; requiring treatment (e.g. infection, bleedings, uncontrolled hypertension despite optimal medical management, HIV, hepatitis, organ transplants, kidney, cardiac and respiratory diseases). 4. Unwillingness to abstain from acid beverages such as orange juice and cola in the morning during afatinib treatment in this study. 5. Patients who are clinical dependent of use of PPIs or other acid reducing drugs, e.g. due to elevated risk for gastro-intestinal bleeding. |
1. Zwangeren of patiënten die borstvoeding geven 2. Patiënten met bekende verminderde medicijnabsorptievermogen (bijv. gastrectomie en achlorhydrie) 3. Bekende ernstige aandoening of medisch instabiele conditie die kan interfereren met de studie; behandeling behoeven (bijv. infectie, bloeding, niet controleerbare hypertensie ondanks optimale behandeling, HIV, hepatitis, orgaantransplantatie, nier-, hart- en longziekte) 4. Niet bereidwillig om zich te willen onthouden van zure dranken zoals jus d'orange en cola gedurende de ochtend van afatinib behandeling gedurende de studie 5. Patiënten met klinische afhankelijkheid van het gebruik van protonpompremmers of andere maagzuurverlagers, bijvoorbeeld door verhoogd risico op gastro-intestinale bloedingen |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the area under the curve of afatinib compared to afatinib concomitantly used with esomeprazole and to afatinib used with esomeprazole 3 hours prior in patients with non-small cell lung cancer. |
De biologische beschikbaarheid van afatinib evalueren bij afatinib gelijktijdig ingenomen met esomeprazol vergeleken met afatinib met esomeprazol 3 uur eerder ingenomen, bij patiënten met niet-kleincellig longkanker. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
End of study |
Einde van de studie |
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E.5.2 | Secondary end point(s) |
1. Other pharmacokinetic outcomes (i.e. clearance, maximum concentration and time to Cmax). 2. To evaluate the incidence and severity of side-effects of treatment with afatinib in absence and presence of esomeprazole. |
1. Andere farmacokinetische uitkomstmaten (bijv. klaring, maximale concentratie, tijd tot Cmax). 2. Evalueren van de incidentie en ernst van bijwerkingen van afatinib met of zonder esomeprazol ingenomen. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
End of study |
Einde van de studie |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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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LVLS |
Laatste visite van de laatste patiënt |
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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 | |
E.8.9.1 | In the Member State concerned days | |