Solid tumors treated with sorafenib (Nexavar®) mono therapy.
Conditions
Interventions
1. Administration of rifampicin and midazolam.
2. Bloodwithdrawal for pharmacokinetics of sorafenib and midazolam.
Sponsors
Erasmus Medical Center; Department of Medical Oncology
Eligibility
Inclusion criteria
Inclusion criteria: • Age ≥18 years; • Histological/ cytological confirmed diagnosis of cancer treated with sorafenib monotherapy • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1. (see appendix A); • A stable dose of sorafenib for at least 2 weeks (to guarantee steady-state); • Adequate hematological functions, absolute neutrophil count (ANC)> 1.0 x 109/L, platelet count ≥ 100 × 109/L); • Adequate renal and hepatic functions defined as serum creatinin <1.25 x ULN; total bilirubin <1.25 x ULN; asparate aminotransferase (AST) and alanine aminotransferase (AST) ≤ 5 x ULN; • PTT ≤ 1.5×ULN and INR < 1.5; • Signed informed consent and amenable to compliance with protocol schedules and testing; • For patients with reproductive potential a reliable method of contraception (excluding oral contraceptive) must be used.
Exclusion criteria
Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: • Pregnant or child nursing patients; • 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; • Major surgery within 2 weeks prior to start of the protocol; • Radiotherapy within the last 2 weeks before start of this study; • Patients who had a liver transplantation prior to sorafenib treatment; • Patients who receive therapeutic anticoagulation therapy. Low dose, non- therapeutic anticoagulation (e.g., low dose warfarin) for catheter prophylaxis only will be permitted; • Patients who receive anti-retroviral therapy for Human Immunodeficiency Virus (HIV). Prophylactic antiviral therapy to prevent Hepatitis B virus (HBV) reactivation or cytokine therapy (e.g. interferon) for Hepatitis C virus infection is allowed; • Use of CYP3A4 inhibiting or inducing medication; • Concurrent medication or supplements which can interact with sorafenib.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the influence of OATP1B inhibition, through rifampicin exposure, on the metabolism and plasma pharmacokinetics of sorafenib and its metabolites. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To compare the incidence and severity of side effects of treatment with sorafenib in the absence and presence of rifampicin (interim-analysis after 4 patients). 2. To study the influence of genetic polymorphisms in OATP1B involved in the metabolism of sorafenib. 3. To assess the degree of CYP3A induction after administration of rifampicin for two days by measuring midazolam clearance. | — |
Contacts
Public ContactRon H.J. Mathijssen
Erasmus MC Rotterdam – Daniel den Hoed Cancer Center Department of Medical Oncology Room G4-80
Outcome results
None listed