Sorafenib Administered Using a High-dose, Pulsatile Regimen: a Phase I Exposure Escalation Study
Status:
Completed
Trial end date:
2017-12-27
Target enrollment:
Participant gender:
Summary
Sorafenib is an oral anticancer drug and inhibits multiple protein kinases important for
tumor growth and metastases, including VEGFR, PDGFR, and RAF kinases. In daily clinical
practice it is currently used at a dose of 400 mg twice daily in a continuous schedule. In
this phase I study patients will be treated with a new dosing schedule of sorafenib: i.e. a
high-dose, pulsatile schedule. The tolerability and safety of this new schedule is examined
in exposure escalation cohorts based on a target plasma AUC0-12h (area under the curve).
Exposure escalation cohorts are used instead of conventional dose escalation cohorts because
the effect of a drug is dependent of its AUC levels and large differences in plasma sorafenib
AUC0-12h have previously been shown between patients treated at the same dose level. Using
pharmacokinetic monitoring, the sorafenib dose will be adjusted to a target plasma AUC0-12h.
The escalation cohorts consist of 3-6 patients per exposure level starting with a target
plasma sorafenib AUC0-12h level of 25-50 mg/L/h. After the determination of the maximum
tolerated AUC0-12h, 10 additional patients will be entered into an expansion cohort. In the
expansion cohort the patients will be treated with a weekly pulse of sorafenib at the maximum
tolerated AUC0-12h for further assessment of safety and preliminary exploration of efficacy.