This Phase 1 study will be conducted in an open-label, non-randomized, dose-escalation design
in subjects with advanced, metastatic or refractory solid malignancy who are not candidates
for standard therapy. The study drugs are sorafenib and eribulin mesylate.
Up to 24 subjects with solid tumors will participate in the dose escalation part of the
study, and once the maximum tolerated dose is defined, up to 30 subjects with advanced,
metastatic or refractory solid tumors will participate in the expansion phase of the study.
Eribulin (mesylate) will be administered intravenously at a fixed dose of 1.4 mg/m2 on Days 1
and 8 of 21-day Cycles.
The starting sorafenib dose (Dose Level 1) is 200 mg twice daily. Sorafenib is given orally,
continuously on days 11 to 21 of Cycle 1, and from Day 1 to Day 21 of all subsequent cycles.
If 200 mg sorafenib twice daily is tolerated with eribulin, the sorafenib dose will be
escalated sequentially to 200 mg morning dose and 400 mg evening dose (Dose Level 2) in a new
cohort. If Dose Level 2 is tolerated, a second dose escalation to 400 mg twice daily (Dose
Level 3) will be studied in a new cohort. If the starting dose of sorafenib is not tolerated
with eribulin, the sorafenib dose will be de-escalated to 200 mg once daily in a new cohort.
Subjects will need to receive two cycles of eribulin plus sorafenib therapy and safety data
for the first and second cycle needs to be available before the start of the next cohort.