Phase I study of NBTXR3 nanoparticles, in patients with advanced soft tissue sarcoma (STS).

Preoperative radiotherapy for extremity soft tissue sarcoma; past, present and future perspectives on dose fractionation regimens and combined modality strategies

“…Preliminary results of other phase I trials have been presented in abstract form: sunitinib in combination with 28 × 1.8 Gy [64], and hafniumoxide nanoparticles (NBTXR3, intended to enhance the RT effect by local electron deposits) in combination with 25 × 2 Gy [65]. Because of the promising results observed with intra-tumoral injection of NBTXR3 nanoparticles just prior to preoperative RT followed by surgery in a phase I trial (showing a median percentage of residual malignant visible cells of 25%), a phase II/III trial has just started comparing preoperative radiotherapy to 50 Gy to the same RT schedule combined with intra-tumoral NBTXR3 (Trial Identifier NCT02379845).…”

Nanoparticles in the clinic

“…Hafnium oxide nanoparticles (NBTXR3), developed by Nanobiotix, utilize an external radiation source to enhance cell death at the radiation site via release of electrons. In preclinical animal models, NBTXR3 showed antitumor effects with similar to standard radiation therapies and early clinical results suggest a good safety profile in humans as well as encouraging antitumor results . As these therapies attack cancer cells via a physical mechanism, it is likely that they will benefit from synergistic pairings with other, more chemical‐based, treatments.…”

The role of recent nanotechnology in enhancing the efficacy of radiation therapy

“…First data on a phase I clinical trial using Hafnium oxide nanoparticles (NBTXR3) in combination with radiotherapy in patients with soft tissue sarcoma of the extremity revealed promising results with regards to its safety and antitumor activity [132]. A follow-up phase II/III clinical trial (NCT02379845) has recently started.…”

“…Nanoparticle clinical studies with published results 9% of patients: CR, 53% PR, additional 19% achieved a best response of stable disease for > 16 weeks; very well tolerated with neutropenia and leukopenia being the most common toxicities and fatigue the most common nonhemotoxic toxicity PFS = 10.4 months, ORR = 75.9%, 27.6% CR, 48.3% PR, 17.2% stable disease, 6.9% progressive disease; acceptable toxicity with 27.6% grade 3 or 4 toxicity Minimal side effects, majority of patients showed stable disease, accumulation of p53 transgene in metastatic tumors, status of 1 patient changed from unresectable to resectable anemia and 11% neutropenic fever; median OS = 7.3 months, median PFS = 1.7 months, 5% PR, 32% stable disease, 63% progression or death [23]A C C E P T E D M A N U S C R I P T Well tolerated with main grade 1-2 toxicities, adequate bioavailability over 5 weeks of RT with no leakage into healthy tissue, antitumor activity in different sarcoma subtypes[132] CALAA-01: cyclodextrin polymer-based nanoparticle formulation containing RRM2 siRNA; compl. : completed; CR: complete remission; HER2: human epidermal growth factor receptor 2; NBTXR3: functionalized hafnium oxide nanoparticles; neg.…”