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

Improving CNS penetration of radiolabeled TKI PET tracers through PgP/BCRP inhibition - M14EEP:Improving CNS uptake of TKI PET tracers through PgP/BCRP inhibition

Status

Active, not recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON41107

Enrollment

Registered

2014-03-17

Start date

2014-09-19

Completion date

Unknown

Last updated

2024-04-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Prevention and treatment of brain tumors and metastases

Interventions

None listed

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

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

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.

Design outcomes

Primary

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

Measure

Time frame

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

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Secondary

Measure	Time frame
Secondary objectives of this study are the determination of labeling efficiency, radiochemical purity, sterility, pyrogen and radiation safety of the newly developed radiolabeled TKI PET tracers.	—

Countries

Netherlands

Outcome results