Effect of Sorafenib on ccRCC Uptake of Radiolabeled Bevacizumab or cG250
Status:
Completed
Trial end date:
2012-06-01
Target enrollment:
Participant gender:
Summary
Sorafenib is a tyrosine kinase inhibitor that is registered for the treatment of metastasized
clear cell Renal Cell Carcinoma (ccRCC). It inhibits signal transduction of the Vascular
Endothelial Growth Factor Receptor (VEGFR) and the Platelet Derived Growth Factor Receptor
(PDGFR). In the tumorigenesis of ccRCC, VEGF and PDGF are upregulated due to the defective
Von-Hippel-Lindau (VHL) gene. CcRCC has a high Interstitial Fluid Pressure (IFP) and Tumor
Microvascular Density (TMD), hampering the delivery of chemotherapeutics and monoclonal
antibodies (mAbs). It was hypothesized that antiangiogenic compounds decrease tumor IFP and
TMD, thus normalizing tumor vasculature, before diminishing tumor vasculature. Bevacizumab is
an anti-VEGF mAb which depletes soluble VEGF from plasma, depriving VEGFR of its ligand.
Chimeric monoclonal antibody cG250 recognizes carbonic anhydrase IX (CAIX), an antigen that
is abundantly expressed in Renal Cell Carcinoma (RCC) and has limited expression in normal
tissue. The aim of this study was to investigate the effect of Sorafenib on ccRCC physiology,
by determining tumor uptake of 111In labeled cG250 or 111In labeled Bevacizumab.