First Human Study Testing a New Radio Enhancer Using Nanoparticles (NBTXR3) Activated by Radiation Therapy in Patients with Locally Advanced Soft Tissue Sarcomas
Mené en France sur 22 patients atteints d'un sarcome des tissus mous de stade localement avancé, cet essai de phase I évalue la faisabilité d'une radiothérapie externe pré-opératoire comportant au préalable une injection intratumorale de nanoparticules d'oxyde d'hafnium pour amplifier les effets des rayonnements ionisants
Purpose : This Phase 1 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 magnetic resonance imaging (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 post-injection, and EBRT initiated (50 Gy over 5 weeks). Surgery was performed 6-8 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 pathological 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.