Background: Angiosarcomas (AS) account for 2-3% of all soft tissue sarcomas. About 60% develop at the skin, and radiation-induced AS following breast cancer therapy represent a characteristic feature. In metastatic or locoregionally advanced AS paclitaxel may induce tumor response. Data also show positive effects of VEGF-inhibiting drugs in AS patients. Thus, the combined application of chemotherapy and TKI seems warranted. Methods: This multicentre, open, prospective, single-armed phase II trial (NCT02212015) evaluates efficacy and safety of combined pazopanib (800mg/d) and paclitaxel (70mg/msq d1, 8, 15 of a 28d cycle) in advanced or metastatic AS. Primary endpoint is PFS at 6 mos. after start of therapy. Statistical analysis looks for 6 m-PFS > 35% using RECIST 1.1. The trial is conducted in two steps with an interim futility analysis. Twenty-six patients were recruited (23 f, 3 m, median age 60.5 yrs), ECOG 0/1: n = 20/6 (80%/20%), 5 pts had local tumor progression, 21 pts (80.8%) showed metastatic disease, tumor description see table 1. Results: At interim analysis, the full analysis set consisted of 26 pts who received study medication at least once. The number of successes (6-m PFS yes) was n = 12 (46%). We had to adapt type-I-error for overrunning the pre-specified interim sample size, prompting a boundary of 17/26 pts with 6-m PFS, which the study did not meet (2-sided Clopper-Pearson CI). The formal decision was to stop the trial for futility. Analysing the non-responders showed that none of pts with hepatic involvement and 2nd AS after total body irradiation (TBI) did profit from study therapy. Conclusions: Combined paclitaxel and pazopanib is an active treatment in AS particularly in tumors located superficially. Patients with visceral metastases and those with hepatic angiosarcoma after TBI did not respond. The study protocol is about to be amended with refined inclusion citeria. Clinical trial information: NCT02212015