No registrations found.
ID
Source
Brief title
Health condition
Cancer
Brain metastases
Tyrosinse Kinase Inhibitors
Drug Transporters
Sponsors and support
Intervention
Outcome measures
Primary outcome
Improved CNS penetration of 11C erlotinib after PGP/BCRP inhibitor administration.
Secondary outcome
NA
Background summary
The primary objective of this study is to obtain clinical proof of principle that the addition of a PgP/BCRP inhibitor
increases CNS concentrations of tyrosine kinase inhibitors by inhibition of drug efflux transporter function in the blood
brain barrier.
Every patient will undergo two PET scans. For both scans an intravenous bolus of [11C]erlotinib will be administered. For
the second scan patients will be instructed to take 1000 mg of a PGP/BCRP inhibitor orally. This will enable us to measure the uptake of [11C]erlotinib in the brain with and without PgP/BCRP inhibition.
Study objective
The primary objective of this study is to obtain clinical proof of principle that the Addition of a PgP/BCRP inhibitor
increases CNS concentrations of tyrosine kinase inhibitors by inhibition of drug efflux transporter function in the blood
brain barrier
Study design
11C-erlotnib PET scan on 2 successive days.
Follow up visit 7+-2 days afterwards.
Intervention
- 2 11C-erlotinib PET scans. 1 with administration of a PGP/BCRP inhibitor and 1 without.
- 1 MRI of the brain.
Department of Medical Oncology<br>
Plesmanlaan 121
N. Steeghs
Amsterdam 1066 CX
The Netherlands
+31 (0)20 5122570
n.steeghs@nki.nl
Department of Medical Oncology<br>
Plesmanlaan 121
N. Steeghs
Amsterdam 1066 CX
The Netherlands
+31 (0)20 5122570
n.steeghs@nki.nl
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.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL4629 |
| NTR-old | NTR4780 |
| Other | M14EEP : 2014-000281-21 |