Act.In.Sarc

Act.In.Sarc (study NBTXR3-301) was an open-label, randomised, multicentre phase 2/3 trial of NBTXR3, a hafnium oxide nanoparticle radioenhancer injected once into the tumour, in adults with locally advanced soft-tissue sarcoma of the extremity or trunk wall who needed preoperative radiotherapy. 180 eligible patients were randomised 1:1, stratified by histological subtype (myxoid liposarcoma versus others), to NBTXR3 (an injection volume equal to 10 percent of the baseline tumour volume, at 53.3 g/L) followed by external-beam radiotherapy of 50 Gy in 25 fractions, or to the same radiotherapy alone; both arms then had surgery. The primary endpoint was pathological complete response, judged by a central pathology review board under EORTC guidelines in the intention-to-treat full analysis set.

Of 179 patients who started treatment, 176 were analysed for the primary endpoint (87 NBTXR3, 89 radiotherapy alone) after three were found to be ineligible. Pathological complete response occurred in 14 of 87 patients (16 percent) with NBTXR3 and 7 of 89 (8 percent) with radiotherapy alone (p=0.044; The Lancet Oncology 2019). Postoperative wound complication was the most common grade 3 or 4 treatment-emergent event in both arms (9 percent each). Injection-site pain and hypotension (4 percent each) were the most common grade 3 or 4 events related to NBTXR3 administration; serious adverse events occurred in 39 percent versus 30 percent, and there were no treatment-related deaths.