Theranostic AGuIX nanoparticles as radiosensitizer: A phase I, dose-escalation study in patients with multiple brain metastases (NANO-RAD trial)

Background and purposeBrain metastasis impacts greatly on patients’ quality of life survival. The phase I NANO-RAD trial assessed the safety maximum tolerated dose systemic administration a novel gadolinium-based nanoparticle, AGuIX, in combination with whole brain radiotherapy patients multiple metastases not suitable for stereotactic radiotherapy.Materials methodsPatients measurable received escalating doses AGuIX nanoparticles (15, 30, 50, 75, or 100 mg/kg intravenously) day initiation WBRT (30 Gy 10 fractions) 5 cohorts 3 each. Toxicity was using NCI Common Terminology Criteria Adverse Events v4.03.ResultsFifteen 354 were included. No dose-limiting toxic effects observed up to mg/kg. Plasma elimination half-life similar all groups (mean 1.3 h; range 0.8–3 h). Efficient targeting (T1 MRI enhancement, tumor selectivity) persistence contrast enhancement from primary melanoma, lung, breast, colon cancers. concentration after proportional injected dose. Thirteen 14 evaluable had clinical benefit, either stabilization reduction volume. analysis showed significant correlation between response, thus supporting radiosensitizing effect.ConclusionCombining is safe feasible. specifically targets retained within tumors 1 week; ongoing II studies will more definitively assess efficacy.