Phase II clinical trial of Linsitinib launched in patients with advanced Ewing sarcoma

EUROSARC, European Clinical trials in Rare Sarcomas within an integrated translational trial network, has launched a phase II trial of Linsitinib for patients with relapsed and/or refractory Ewing Sarcoma. The trial, EORTC 1225 / OCTO 038, aims to establish pharmacodynamic responses in Ewing sarcoma tumors to Linsitinib using functional imaging and biopsies, and toxicity and clinical outcomes.

Prof Jean-Yves Blay, Director of EUROSARC and of the participating Eurosarc center at the Centre Léon Bérard in Lyon (France) adds, "Our understanding of Ewing sarcoma continues to expand, and recent research indicates that blocking the Insulin-like Growth Factor 1 Receptor could be an effective treatment strategy. In fact, early phase I/II trials using agents (R1507 and Figitumumab) that target only this receptor have shown 10-15% partial response rates, and a number of patients have had prolonged disease stabilization. However, not all patients respond to this treatment, and the reason why only a small subset of patients respond, and the majority does not, is unclear."

Prof. Bass Hassan of Oxford University and Oxford University Hospitals NHS Trust - Churchill Hospital and Chief Investigator of this study says, "The reason for this heterogeneity of response could be any number of things: partial signal pathway inhibition at the tumor level, inherent resistance in Ewing sarcoma cells, or the presence of alternative pathway activation. To resolve this and develop more effective treatment, the EORTC 1225 / OCTO 038 trial aims to establish pharmacodynamic responses in Ewing sarcoma tumors using functional imaging with FDG (2-deoxy-2-[18F]fluoro-D-glucose PET/CT) and repeat post treatment biopsies, as well as toxicity and clinical outcome to Linsitinib, the anti-Insulin-like growth factor I / insulin receptor kinase blocking agent being used as treatment."

Primary endpoints for this study are FDG uptake response (standardized uptake value), biomarker responses in tumor biopsies, Adverse Events, and laboratory abnormalities. The study is based on a Bayesian adaptive design, and so subject to interim analysis and stopping rules based on a novel statistical plan.