malignancy sarcoma gastrointestinal stromal tumour
Conditions
Interventions
This pharmacokinetic study, we would like to expose GIST patients at steady-state concentrations of imatinib to rosuvastatin. We will compare the (plasma) pharmacokinetics of imatinib and its metaboli
Sponsors
Prof. Dr. J. Verweij
Erasmus MC - Daniel den Hoed Cancer Center
Groene Hilledijk 301
3075 EA Rotterdam
Eligibility
Inclusion criteria
Inclusion criteria: 1. Histological or cytological confirmed diagnosis of any form of irresectable and/or metastatic GIST, which is already treated with imatinib for a consecutive period of at least 4 weeks; 2. Age ³ 18 years; 3. WHO performance £ 1 (see appendix B); 4. Adequate hematological functions (ANC > 1.5 x 109/L, platelets > 100 x 1012/L); 5. Adequate renal and hepatic functions (serum creatinin < 1.25xULN, bilirubin < 1.25xULN, ALAT and ASAT < 2.5xULN, in case of liver metastasis < 5 ULN; alkaline phosphatase < 5xULN); 6. Written informed consent; 7. Complete initial work-up within four weeks prior to therapy with the combination of imatinib and rosuvastatin.
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating patients; patients with reproductive potential must use a reliable method of contraception (excluding oral contraceptives), if required; 2. Serious illness or medical unstable condition requiring treatment, symptomatic CNS-metastases or history of psychiatric disorder that would prohibit the understanding and giving of informed consent; 3. Use of imatinib therapy less than 4 consecutive weeks; 4. Major surgery within 2 weeks before start of the protocol (to be evaluated by an MD); 5. (Chronic) use of CYP3A and/or P-glycoprotein inhibiting and inducing medication (in particular cyclosporine, which may result in a severe rise of rosuvastatin plasmaconcentration) dietary supplements, or other inhibiting compounds (see Appendix D); 6. Unwillingness to change medication, or no adequate alternatives available, when drugs are taken that are known to interact with CYP3A and/or ABCB1 and/or ABCG2; 7. Asian patients; 8. Use of statins 4 weeks prior to study entry; 9. Patients suffering from myopathy (CK > 10 x ULN associated with muscle symptoms).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| -To investigate the influence of rosuvastatin on the plasma pharmacokinetics of imatinib (and its metabolite CGP74588) in GIST cancer patients. | — |
Secondary
| Measure | Time frame |
|---|---|
| - To correlate genetic polymorphisms in enzymes and drug transporting pumps [40,41] with imatinib pharmacokinetics and adverse effects in GIST cancer patients (according to METC protocol 02-1002). - To study possible side-effects due to the combination treatment of imatinib and rosuvastatin. | — |
Contacts
Public ContactKarel Eechoute
Erasmus MC Rotterdam – Daniel den Hoed Cancer Center Department of Medical Oncology Room G4-80
Outcome results
None listed