Summary

The enclosed abstract was presented at the 13th Journées cancéropole Grand Sud-Ouest at Poitiers. The abstract Hafnium oxide nanoparticles as an emergent promising treatment for solid tumors describes how hafnium oxide nanoparticles were designed at the nanoscale in the form of crystalline 50nm-particles to efficiently absorb ionizing radiation and increase the radiation dose deposited – “hot spots” of energy deposit – from within the tumor cells for efficient cell killing.

Hafnium oxide nanoparticles (NBTXR3), administered as a single intratumoral injection and activated by radiotherapy, is currently evaluated in a phase II/III clinical trial in soft tissue sarcoma (STS) [NCT02379845], and in phase I/II clinical trials for head and neck [NCT01946867], prostate [NCT02805894], liver [NCT02721056; NCT02721056] and rectum cancers [NCT02465593]. So far, patients treated with NBTXR3 received radiotherapy as planned and showed a very good local safety profile.

Summary

Purpose: This phase I study aimed to determine the recommended dose (RD), safety profile, and feasibility of a procedure combining intratumoral injection of hafnium oxide nanoparticles (NBTXR3; a radioenhancer) and external beam radiotherapy (EBRT) for preoperative treatment of adults with locally advanced soft tissue sarcoma (STS).

Experimental Design: Patients had a preoperative indication of EBRT for STS of the extremity or trunk. Baseline tumor volume (TV) was calculated by MRI. NBTXR3 was injected percutaneously into tumors at 53.3 g/L. Dose escalation was based on four levels equivalent to 2.5%, 5%, 10%, and 20% of baseline TV. NBTXR3 was visualized in the tumor 24 hours postinjection, and EBRT was initiated (50 Gy over 5 weeks). Surgery was performed 6 to 8 weeks after EBRT completion.

Results: Twenty-two patients completed NBTXR3 injection, EBRT, and surgery and were followed for a median 22 months (range, 6–40). At NBTXR3 20% of TV, two dose-limiting toxicities occurred: injection-site pain and postoperative scar necrosis. The RD was defined as 10%. No leakage of NBTXR3 into surrounding tissues occurred; intratumor NBTXR3 levels were maintained during radiotherapy. At the RD, median tumor shrinkage was 40% (range 71% shrinkage, 22%increase);median percentage of residual viable tumor cells was 26% (range, 10%–90%). Patients receiving 20% of TV demonstrated pathologic complete responses. Seven grade 3 adverse events occurred, which were reversible.

Conclusion: A single intratumoral injection of NBTXR3 at 10% of TV with preoperative EBRT was technically feasible with manageable toxicity; clinical activity was observed. Clin Cancer Res; 1–10. 2016 AACR.