Determining the Clinical Relevance of the inTeraction Between AprepitaNt aNd EtoposiDe

Study Overview
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Brief Summary
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Rationale: In pharmacokinetic studies, aprepitant was shown to be a moderate inhibitor of CYP3A4 activity. Etoposide is metabolised by CYP3A4. Objective: to investigate the absence of a clinical relevant interaction between aprepitant and etoposide in TC patients treated with (B)EP. Study design: A single centre, prospective, paired observational pharmacokinetic study in 12 patients with TC who are treated with etoposide during 5 days in combination with cisplatin with or without bleomycin conform the standard BEP or EP-protocol and who will be treated with aprepitant from day 3 until day 7 according to the routine antiemetic protocol. The effect of aprepitant on etoposide will be investigated within the same patient. In this study the patient will serve as its own control.

Official Title
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Determining the Clinical Relevance of the inTeraction Between AprepitaNt aNd EtoposiDe; an Observational Pharmacokinetic Study

Conditions
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Testicular Cancer

Intervention / Treatment
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* Other: Blood sampling - Pharmacokinetic assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with TC who will start or already started treatment with (B)EP Age of at least 18 years Patients from whom it is possible to collect blood samples Patients who are able and willing to give written informed consent prior to screening Exclusion Criteria: Patients who are co-treated with drugs that could interfere with the metabolism of etoposide (including drugs classified as a weak, moderate or strong CYP3A4 inhibitor OR weak, moderate and strong inducers of CYP3A4 according to the table based on the Flockhart table (Appendix 1) less than 30 days prior to study or during the study. Creatininclearance <40 ml/min Severe liver dysfunction (bilirubin>ULN)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Single Arm<br>The participating patients are treated according to local standard treatment (consisting of etoposide 100mg/m2 and cisplatin 20 mg/m2 during 5 consecutive days). Anti-emetic treatment with aprepitant will be given during days 3 to 7. | Other: Blood sampling - Pharmacokinetic assessment<br>* Two pharmacokinetic assessments will be performed (on day 2 and day 4). Each pharmacokinetic assessment consists of 10 samples (5 ml blood).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exposure to etoposide | Etoposide exposure (AUC0-24hr) with and without cotreatment with aprepitant | 24 hours after administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aprepitant, etoposide, pharmacokinetic interaction, CYP3A4, clinical relevant interaction, pharmacokinetics