Cancer, gastrointestinal stromal tumor, imatinib, absolute bioavailability
Conditions
Interventions
Intravenous injection with stable isotople labeled imatinib and subsequent blood collection
Sponsors
Antoni van Leeuwenhoek
Eligibility
Inclusion criteria
Inclusion criteria: 1. Locally advanced or metastatic cancer; 2. On imatinib treatment at a stable dose of 400 mg once daily in the morning for at least 7 days (steady state plasma concentration) 3. Age ≥ 18 years; 4. Able and willing to give written informed consent; 5. WHO performance status of 0, 1 or 2; 6. Able and willing to undergo blood sampling for PK analysis 7. Minimal acceptable safety laboratory values > a. ANC of ≥ 1.5 x 109 /L b. Platelet count of ≥ 100 x 109 /L c. Hepatic function as defined by serum bilirubin ≤ 2 x ULN, ALAT and ASAT ≤ 5 x ULN d. Renal function as defined by glomerular filtration rate (GFR MDRD) > 40 ml/min/1.73m2 8. Able and willing to get two lines for intravenous infusion (one for microdose infusion and one for PK sampling)
Exclusion criteria
Exclusion criteria: Any treatment with investigational drugs within 30 days or 5 half-lives prior to receiving the investigational treatment; 2. Any treatment with inhibitors of CYP3A4 (e.g. boceprevir, claritromycine, erytromycine, indinavir, itraconazol, ketoconazol, ritonavir and voriconazol), inhibitors of Pgp (e.g. ciclosporine, kinidine and verapamil), inhibitors of BCRP (e.g. lapatinib), inductors of CYP3A4, Pgp or BCRP; 4. Woman who are pregnant or breast feeding; 5. Patients suffering from any known disease or dysfunction that might influence the dissolution and/or absorption of imatinib (e.g. inflammatory bowel disease)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To ascertain whether the absolute bioavailability of oral imatinib (Glivec®) at steady state can be calculated using LC-MS/MS after concomitant administration of a single 100 µg microdose of stable isotope labeled imatinib (imatinib-d8). | — |
Contacts
Public ContactN. Steeghs
The Netherlands Cancer Institute Department of Medical Oncology Plesmanlaan 121
Outcome results
None listed