Acid-reducing drugs, such as PPIs, may profoundly decrease solubility and, as a result, (negatively) affect the bioavailability of afatinib. Since a PPI is often used concomitantly during afatinib therapy, this DDI confronts physicians, patients,…
ID
Bron
Verkorte titel
Aandoening
NSCLC
non small cell lungcarcinoma
NKCLC
niet-kleincellig longcarcinoom
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
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.
Achtergrond van het onderzoek
In The Netherlands, afatinib is registered for the treatment of advanced lung cancer. A majority of the patients benefit of the therapy, with lower rates of cancer cell proliferation. Many cancer patients have gastric complaints such as reflux and have to use proton pump inhibitors, or get proton pump inhibitors prescribed to prefent gastric complaints. Concomitant use of afatinib with a proton pump inhibitor could lower afatinib bio-availability by increasing pH, and thus preventing absorbtion of afatinib in the intestinal tract. Nevertheless, to date, this interaction has never been studied.
Doel van het onderzoek
Acid-reducing drugs, such as PPIs, may profoundly decrease solubility and, as a result, (negatively) affect the bioavailability of afatinib. Since a PPI is often used concomitantly during afatinib therapy, this DDI confronts physicians, patients, and pharmacists with major challenges. So, it is highly relevant to study the effects of this DDI on afatinib bioavailability in real patients. In case a clinically relevant PK interaction is found, dosing adjustments could be made to guarantee adequate drug concentrations of afatinib. In this study we will also evaluate the influence of time of esomeprazole intake (3h before afatinib and concomitantly) so we could give an advice on time-depending dosing when a relevant DDI is found. On the other hand, when PPIs do not affect afatinib bioavailability, a DDI can be ruled out. Therefore, in this study we will evaluate the impact of esomeprazole during afatinib treatment in patients with NSCLC.
Onderzoeksopzet
Patients will be admitted to the hospital for a total of three days, during which pharmacokinetic blood withdrawals will be performed. Patients will be randomized into 2 sequence groups consisting of three phases. In 2 phases patients are also treated with esomeprazole for a total of 28 days.
Onderzoeksproduct en/of interventie
Esomeprazole 40mg once daily, in a total of 10 days. Afatinib is taken in accordance to standard of care. Esomeprazole will be taken concomitant and 3 hours prior afatanib intake, each period for 5 days.
Publiek
Ron H.J. Mathijssen
Groene Hilledijk 301
Rotterdam 3075 EA
The Netherlands
+31 (0)10 7041338, buzzer 229
a.mathijssen@erasmusmc.nl
Wetenschappelijk
Ron H.J. Mathijssen
Groene Hilledijk 301
Rotterdam 3075 EA
The Netherlands
+31 (0)10 7041338, buzzer 229
a.mathijssen@erasmusmc.nl
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
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.
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
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.
Opzet
Deelname
Opgevolgd door onderstaande (mogelijk meer actuele) registratie
Geen registraties gevonden.
Andere (mogelijk minder actuele) registraties in dit register
Geen registraties gevonden.
In overige registers
| Register | ID |
|---|---|
| NTR-new | NL6336 |
| NTR-old | NTR6652 |
| Ander register | : MEC 2017-251 |