Pazopanib (Votrient) is registered for the treatment of patients with advanced renal cell carcinoma and patients with soft tissue sarcoma who have received prior chemotherapy. It is administered at a fixed oral dose of 800 mg once daily (OD) regardless of size, age and clinical condition. It is absorbed from the gastrointestinal tract with an oral bioavailability of \~21%. Pazopanib is practically insoluble and highly permeable. When ingested with high fat food the pazopanib exposure (area under the concentration time curve (AUC)) is doubled. Common adverse effects are diarrhea and nausea. This might be caused by the non-absorbed proportion of pazopanib. A reduced dose taken with food could be a possible approach to reduce these side effects. Therefore the investigators initially want to determine the equivalent reduced dose of pazopanib when taken with a continental breakfast. Thereafter the investigators want to investigate whether the intake with food reduces the frequently reported side effects nausea and diarrhea.
Pazopanib (Votrient) is a multi targeted tyrosine kinase inhibitor of vascular endothelial growth factor receptor, (VEGFR-1, -2 en -3), platelet-derived growth factor receptor (PDGFR-α and -β), and stem cell factor receptor (c-KIT). Pazopanib is registered for the treatment of patients with advanced renal cell carcinoma and patients with soft tissue sarcoma who have received prior chemotherapy. It is administered at a fixed oral dose of 800 mg OD regardless of size, age and clinical condition. It is absorbed from the gastrointestinal tract with an oral bioavailability of \~21%. Pazopanib is practically insoluble and highly permeable. When ingested with high fat food the pazopanib exposure (area under the concentration time curve (AUC)) is doubled. Common adverse effects are diarrhea and nausea. This might be caused by the non-absorbed proportion of pazopanib. A dose reduction when ingested with food could be a logical approach to reduce these side effects; however this is not tested in patients yet. Therefore we want to perform a bioequivalent study to investigate what dose with a continental breakfast equals the dose of 800 mg in fasted conditions (study part A). In part B of the study we want to investigate whether the intake with food reduces the frequently reported side effects.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
78
pazopanib 800mg OD without food
pazopanib 600mg OD with food
RadboudUMC
Nijmegen, Gelderland, Netherlands
Area under the plasma concentration versus time curve (AUC) of pazopanib
Determination of AUC of pazopanib when taken with a continental breakfast compared to 800 mg in fasted state (geometric mean ratio will be determined)
Time frame: 4 weeks
number of side effects
Number of side effects will be compared for the two treatments (with and food.
Time frame: 2 months
questionnaire
Preference of patients (by questionnaire): intake of pazopanib with or without
Time frame: 2 months
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