Phase I Study Of Pazopanib (Paz) In Combination With Pci-24781 (Pci) In Patients (Pts) With Metastatic Solid Tumors With New Tumor Proliferation Imaging Correlates In Renal Cell Carcinoma (Rcc) And Sarcoma.

TPS2623 Background: PAZ is a multi-targeted tyrosine kinase inhibitor of VEGFR, PDGFR, and C-KIT, approved for metastatic RCC and refractory sarcoma based on phase III data showing prolonged PFS (JCO 2010;28:1061-8 and Lancet 2012;379:1879-86). PCI is a potent pan-HDAC inhibitor (pan-HDACi), observed in cell lines to change regulation of genes involved in cell signaling, apoptosis, proliferation, differentiation, and angiogenesis (Anticancer Res 2011;31:1115-23). Pre-clinical models suggest epigenetic modification with an HDACi potentiates PAZ’s efficacy by causing chromatin instability and gene expression changes involved in drug resistance (Can Res 2005;65:3815-22 and BJC 2009;100:758-63). We therefore designed a Phase Ia/b clinical trial combining PCI with PAZ in pts with advanced solid tumors, with an expansion cohort for preliminary efficacy in RCC and sarcoma. Methods: Primary objective of this phase Ia/b study is to evaluate the safety and tolerability of the combination of PAZ and PCI to determine...