Therapeutic Drug Monitoring of BRAF- and MEK-inhibitors in a Real Life Cohort of Melanoma Patients

Conditions: cancer
malignancy
10040900

Registration Number: NL-OMON38707

Lead Sponsor: Antoni van Leeuwenhoek Ziekenhuis

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 120

Inclusion Criteria

• All eligible patients (starting or already using) using vemurafenib, dabrafenib and/or trametinib for treatment of cancer. (Patients that are in a (sponsored) clinical trial that receive dabrafenib and/or trametinib will not be included, unless allowed by the other protocol);
• Age 18 years or >18 years;
• Patients from whom it is possible to collect blood samples;
• Patients that are able and willing to undergo a finger prick for dried blood spot sampling;
• Patients that are able and willing to give written informed consent;

Exclusion Criteria

The study objective is to monitor vemurafenib, dabrafenib and trametinib therapy in a *real life* cohort of patients. Therefore no strict exclusion criteria will be used.

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>To describe the PK variability in exposure to vemurafenib, dabrafenib and<br /><br>trametinib and relationship with treatment outcome (Radiological tumor<br /><br>assessments as per RECIST Version 1.1) and toxicity (graded on basis of the<br /><br>National Cancer Institute Common Toxicity grading Criteria for adverse events1<br /><br>(CTC version 4.03)) in a real life cohort.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>• To evaluate the specific influence of different parameters on variability in<br /><br>pharmacokinetics and -dynamics.<br /><br>-To identify the genotypes of drug metabolising enzymes and drug<br /><br>transporters to evaluate if these genotypes influence pharmacokinetics and -<br /><br>dynamics.<br /><br>-To identify drug metabolites, which might influence<br /><br>pharmacokinetics and -dynamics, and to elucidate the metabolic pathway(s).<br /><br>-To monitor the influence of food intake on the pharmacokinetics.<br /><br>-By quantification of the levels of vemurafenib and dabrafenib in<br /><br>skin and plasma samples, we will investigate the relationship between drug skin<br /><br>concentrations and the development of cutaneous squamous cell carcinoma (CSCC)<br /><br>as side effects.<br /><br>• To validate prospectively the methodology to measure vemurafenib, dabrafenib<br /><br>and trametinib levels in DBS.</p><br>