Phase I and Pharmacokinetics Study of Lapatinib in Combination With Sorafenib in Patients With Advanced Refractory Solid Tumors

NCT00984425 Phase 1 COMPLETED

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.

Details

Lead sponsor	Istituto Clinico Humanitas
Phase	Phase 1
Status	COMPLETED
Enrolment	30
Start date	2009-09
Completion	2013-08

Conditions

• Solid Tumors

Interventions

• Lapatinib and Sorafenib

Primary outcomes

• To determine the dose limiting toxicities (DLTs)and the maximum tolerated dose (MTD) of the combination of Lapatinib and Sorafenib. — 0ne year

Countries

Italy