Study of AUY922 in Metastatic Pancreatic Cancer Who Are Resistant to First Line Chemotherapy

This is a single arm open label Phase II clinical trial evaluating the efficacy of AUY922 in patients with advanced pancreatic cancer who have been previously treated with or are intolerant to first line chemotherapy. The primary objective is to assess the efficacy of this agent by assessing the disease control rate (DCR) (objective response plus prolonged stable disease (\>16 weeks). The current standard therapy for patients who have advanced, metastatic or inoperable pancreatic cancer previously treated with or intolerant to first line chemotherapy is best supportive care. New treatment options are urgently needed. Heat shock protein 90 (HSP90) is an ATP-dependent molecular chaperone protein involved in the stabilization of a number of membrane and intracellular proteins including HER2, BCR-ABL, C-SRC, EGFR, RAF, VEGFR, AKT, and RAS. Many of these proteins are highly expressed in pancreatic adenocarcinoma. AUY922 is a novel isoxazole-based HSP90 inhibitor. AUY922 acts by inhibiting HSP90 ATPase activity (IC50 of 30 nm) and preventing the formation of a multichaperone complex between HSP90 and other heat shock proteins. This then prevents HSP90 from performing its functions on client proteins.