A Study Of Crizotinib Plus VEGF Inhibitor Combinations In Patients With Advanced Solid Tumors.
Status:
Withdrawn
Trial end date:
2013-11-01
Target enrollment:
Participant gender:
Summary
Despite the success of anti-angiogenic therapy in multiple treatment settings, a fraction of
patients are refractory to vascular endothelial growth factor (VEGF) inhibitor treatment
while the majority of patients will eventually develop evasive resistance and exhibit disease
progression while on therapy. It is proposed that mesenchymal-epithelial transition factor
(c-MET) and its ligand hepatocyte growth factor (HGF or scatter factor) contribute
significantly to VEGF inhibitor resistance such that combining a c-MET inhibitor with a VEGF
inhibitor will provide additional clinical activity compared to VEGF inhibitor alone. This
hypothesis will be tested using the cMET/ALK inhibitor, crizotinib, in combination with
individual VEGF inhibitors. Three combinations will be prioritized, namely crizotinib plus
axitinib, crizotinib plus sunitinib and crizotinib plus bevacizumab, with a fourth
combination, crizotinib plus sorafenib to be tested only if crizotinib does not combine with
either axitinib and/or sunitinib.