NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2-3, randomised, controlled trial

Phase 2-3 randomised, multicentre, international, open-label trial in adults with locally advanced soft-tissue sarcoma of the extremity or trunk wall requiring preoperative radiotherapy. Patients were randomised 1:1, stratified by histological subtype (myxoid liposarcoma versus others), to a single intratumoural administration of NBTXR3 (volume 10 percent of baseline tumour volume at 53.3 g/L) before external-beam radiotherapy of 50 Gy in 25 fractions, or radiotherapy alone, followed by surgery. The primary endpoint was pathological complete response by a central pathology review board under EORTC guidelines in the intention-to-treat full analysis set.

Between March 2015 and November 2017, 180 eligible patients were randomised and 179 started treatment (89 NBTXR3, 90 radiotherapy alone); 176 were analysed for the primary endpoint after three were found ineligible. Pathological complete response was noted in 14 of 87 (16 percent) in the NBTXR3 group and 7 of 89 (8 percent) with radiotherapy alone (p=0.044). Postoperative wound complication was the most common grade 3 to 4 event in both groups (9 percent each); serious adverse events occurred in 39 versus 30 percent, with no treatment-related deaths.