Clinical Trial: Effect of Sorafenib on ccRCC Uptake of Radiolabeled Bevacizumab or cG250
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: The Effect of Sorafenib (Nexavar®) on 111-Indium Labeled Chimeric Monoclonal Antibody G250 or 111-Indium Labeled Bevacizumab (Avastin®) Uptake in Patients With Clear Ce
Brief 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.
Detailed Summary:
Sponsor: Radboud University
Current Primary Outcome:
- To determine the effect of sorafenib treatment on 111In-cG250 uptake of the tumor [ Time Frame: pre-surgery ]
- To determine the effect of sorafenib treatment on 111In-bevacizumab uptake of the tumor [ Time Frame: pre-surgery ]
Original Primary Outcome: Same as current
Current Secondary Outcome: Immunohistochemical analysis of CA-IX expression, (p)VHL status, HIF1-a, VEGF and PDGF expression, apoptosis and necrosis of surgical specimen [ Time Frame: within 6 months post-surgery ]
Original Secondary Outcome: Same as current
Information By: Radboud University
Dates:
Date Received: January 3, 2008
Date Started: July 2007
Date Completion:
Last Updated: November 29, 2013
Last Verified: February 2012