SORAVE: A phase I trial to evaluate safety and efficacy of combination therapy with everolimus and sorafenib.

2550 Background: Combined inhibition of signaling pathways interfering with angiogenesis and cell proliferation may overcome mechanisms of drug resistance in tumors. We evaluated the combination of the multikinase inhibitor sorafenib (S) and the mTOR inhibitor everolimus (E) and assessed pharmacodynamic (PD) activity of E by PET. Methods: Patients with relapsed solid tumors received escalating doses of E 2.5-10.0mg/d in a 14 days monotherapy run in phase followed by combination therapy with a fixed dose of S 800mg/d from day 15. Further patients were treated with the MTD in an extension phase. The primary aim was to define a safe and feasible combination treatment regimen. DLT was defined as any drug related toxicity of CTC IV° or requiring hospitalization or interruption of therapy for > 2 weeks within the first 29 days of treatment. Pharmacokinetic (PK) analyses were performed on days 5, 14 and 29 combined with explorative PD assessment of E by FDG-PET on days 1, 5 and 14 of treatment. Efficacy was asse...