Predictive and Pharmacodynamic Biomarker Studies in Tumor and Blood Samples of Patients with Metastatic Sarcoma treated by Tivozanib

Project scope- The Robert H. Lurie Comprehensive Cancer Center in collaboration with The Midwest Sarcoma Partnership is due to conduct a Phase II Study of Tivozanib in Patients with Metastatic and Non­ resectable Soft Tissue Sarcomas. Archival tumor tissue samples and blood samples are to be collected. After staining with hematoxylin and! eosin to confirm the presence of tumor tissue in the biopsy material, the tissue sections will be analyzed by routine immunohistochemistry (IHC) with a standard protocol and using commercially available antibodies for VERGFR1 and VEGFR2. Samples that are positive VEGFI or 2 will be further tested for phospho-VEGFRl or 2 respectively, and these will be correlated with response. If neither VEGFR1 nor VEGFR2 correlates with response, we will look at PDGFR-alpha as it is commonly expressed in sarcoma. Based on limitations of the immunohistochemical approach, we expect to distinguish a minimum of 10-20% change in the expression of these proteins. The remaining slides will be held for potential molecular studies which may include DNA sequencing, RNA seq profiling, etc., as seen fit in the future. Slides will be kept for 10 years and then destroyed if not used. Peripheral blood samples will be collected at baseline, one week after initiation of treatment, and prior to every cycle thereafter. Project Description: Correlate clinical outcome in this Phase II Study of Tivozanib in Patients with Metastatic and Non-resectable Soft Tissue Sarcomas with antibodies for VEGFRI and VEGFR2. Specific goals and objectives- Primary: Determine the progression-free survival, assessed at 12 weeks, for patients treated with tivozanib. Secondary: 1) Determine the overall response rate (defined as CR + PR) 2) Determine the clinical benefit rate (CR + PR + SD) 3) Determine overall survival 4) Correlate clinical outcome with antibodies for VEGFR1 and VEGFR2 5) Assess safety and tolerability