title: First-in-Human Study Testing a New Radioenhancer Using Nanoparticles (NBTXR3) Activated by Radiation Therapy in Patients with Locally Advanced Soft Tissue Sarcomas.
abstract: 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.Conclusions: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; 23(4); 908-17. ©2016 AACR.
authors.affiliation: Institut Curie, PSL Research University, Paris, France. sylvie.bonvalot@curie.fr.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bonvalot
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Le Pechoux
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: De Baere
authors.affiliation: Institut Bergonié, Bordeaux, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Kantor
authors.affiliation: Institut Bergonié, Bordeaux, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Buy
authors.affiliation: Institut Bergonié, Bordeaux, France.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Stoeckle
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Terrier
authors.affiliation: Institut Bergonié, Bordeaux, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Sargos
authors.affiliation: Institut Bergonié, Bordeaux, France.
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Coindre
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lassau
authors.affiliation: Nanobiotix, Paris, France.
authors.forename: Rafik
authors.initials: R
authors.lastname: Ait Sarkouh
authors.affiliation: Nanobiotix, Paris, France.
authors.forename: Mikaela
authors.initials: M
authors.lastname: Dimitriu
authors.affiliation: Nanobiotix, Paris, France.
authors.forename: Elsa
authors.initials: E
authors.lastname: Borghi
authors.affiliation: Nanobiotix, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Levy
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Deutsch
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D005260:Female; D006195:Hafnium / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D008297:Male; D008875:Middle Aged; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D018365:Neoplasm, Residual / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D010087:Oxides / Q000008:administration & dosage / Q000737:chemistry; D011300:Preoperative Care; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012509:Sarcoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D010087:Oxides; C545179:hafnium oxide; D006195:Hafnium