A Phase I Study Of Ombrabulin (O) Combined With Bevacizumab (B) In Patients With Advanced Solid Tumors (Nct01193595)

3080 Background: O is a vascular-disrupting agent derived from combretastatin A4-phosphate that induces rapid but transient tumor vascular shutdown. In experimental models, the combination of O with VEGF-blockade induced more regressions than O alone. This phase I study was performed to determine the maximum tolerated dose (MTD), and assess the overall safety, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary antitumor activity of O plus B. Trial is funded by sanofi. Methods: Patients (pt) with advanced solid tumors, ECOG PS ≤1, and adequate organ function were eligible. Increasing doses of O (mg/m²) was administered intravenously (IV) on day (d) 1; B (5 or 10mg/kg) was administered IV on d2, in 21d cycles (C). A Bayesian design was applied to determine dose escalation steps and MTD. PK sampling was performed in C1 and C2. PD sampling for circulating endothelial cells (CEC) and progenitors (CEP) were performed throughout. Dynamic contrast-enhanced ultrasound (DCE-US) to assess tumor perfusion w...