The Treatment of Lapatinib in Combination With Sorafenib in Patients With Advanced Refractory Solid Tumors
Status:
Completed
Trial end date:
2013-08-01
Target enrollment:
Participant gender:
Summary
Over the last decade, improvements in the investigators' understanding of the molecular basis
of cancer have led to the clinical development of protein kinase inhibitors, which target
pivotal molecules involved in intracellular signaling pathways implicated in tumorigenesis
and tumor progression. Lapatinib is an oral selective and reversible inhibitor of the
tyrosine kinase domain of epidermal growth factor receptor (EGFR) and human epidermal growth
factor receptor type 2 (HER-2), which are both frequently altered in human malignant tumors.
Sorafenib is an oral multi-kinase inhibitor with a dual-action that prevents tumor cell
proliferation and angiogenesis. The investigators suggest that through a complete blockade of
ErbB signaling network it may be possible to ''sensitize'' tumor cells to antiangiogenic
therapy, by lowering the tumor cell survival threshold, while through inhibition of vascular
endothelial growth factor (VEGF) pathway to circumvent the problem of acquired resistance to
EGFR inhibitors. Based on this theoretical rationale we decide to test the combination of
Lapatinib and Sorafenib. This phase I trial will be undertaken to assess the maximum dose
tolerated (MTD), safety/tolerability, pharmacokinetics and antitumor efficacy of this
combination in patients with advanced, recurrent or metastatic solid cancers refractory to
available standard treatment.