Improving CNS penetration of radiolabeled TKI PET tracers through PgP/BCRP inhibitio

Completed

• Conditions: Prevention and treatment of brain tumors and metastases; 10027476

• Registration Number: NL-OMON41107
• Lead Sponsor: Antoni van Leeuwenhoek Ziekenhuis

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Completion: 2016-03-31
• Results First Posted: 2016-05-11
• Last Update Posted: 23 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 7

Inclusion Criteria

The study population consists of cancer patients with advanced or metastatic solid tumors for whom no standard therapy is available or for whom a TKI which is a PgP/BCRP substrate is a standard therapeutic option (erlotinib, sunitinib, imatinib, gefitinib, sorafenib, lapatinib, crizotinib, vemurafenib).

Exclusion Criteria

Known brain metastases;
Patients who have had previous treatment with central nervous system irradiation;
Treatment with the tyrosine kinase inhibitor used as TKI PET tracer within three half lives before the PET scans;
Patients with known alcoholism, drug addiction and/or psychiatric of physiological condition which in the opinion of the investigator would impair study compliance;.
Patients are not allowed to use co-medication with PgP or BCRP modulators (including OTC medication).
Patients are also not allowed to use co-medication which are PgP or BCRP substrates as this may lead to increased toxicity.
Known hypersensitivity to erlotinib, elacridar or any excipients used in the formulation of either IMPs.
Known contra-indications for a MRI scan.

Study & Design

• Study Type: Observational invasive
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary parameter of this study is to obtain clinical proof of principle<br /><br>that the addition of a PgP/BCRP inhibitor increases CNS concentrations of TKIs<br /><br>by inhibition of drug efflux transporter function in the blood brain barrier.<br /><br>This will be determined by measuring the difference in estimated influx,<br /><br>outflux and absolute concentrations of TKI in the brain using dynamic PET<br /><br>evaluation, with and without the addition of a PgP/BCRP inhibitor.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary objectives of this study are the determination of labeling<br /><br>efficiency, radiochemical purity, sterility, pyrogen and radiation safety of<br /><br>the newly developed radiolabeled TKI PET tracers.</p><br>