PRIMARY OBJECTIVE:~I. To determine the recommended phase II dose (RP2D) of hafnium oxide-containing nanoparticles NBTXR3 (NBTXR3) activated by radiotherapy in patients with inoperable, locoregional recurrent non-small cell lung cancer (NSCLC), previously treated with definitive radiation therapy.~SECONDARY OBJECTIVES:~I. To evaluate the safety and feasibility of reirradiation with NBTXR3 in patients with inoperable, locoregionally recurrent NSCLC.~II. To evaluate the anti-tumor response of reirradiation with NBTXR3 in patients with inoperable, locoregionally recurrent NSCLC.~III. To evaluate time-to-event outcomes after reirradiation with NBTXR3 in patients with inoperable, locoregionally recurrent NSCLC~EXPLORATORY OBJECTIVE:~I. To assess biomarkers of response in patients treated with NBTXR3/radiation therapy (RT).~OUTLINE: This is a dose-escalation and dose-expansion study of NBTXR3.~Patients receive NBTXR3 intratumorally (IT) or intranodally on day 1. Within 15 days, patients undergo RT 5 times weekly (Monday-Friday) over 3 weeks for a total of 10-15 fractions.~After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for up to 5 years.
This phase I trial investigates the best dose and side effects of NBTXR3 when given together with radiation therapy for the treatment of non-small cell lung cancer that cannot be treated by surgery (inoperable) and has come back (recurrent). NBTXR3 is a radio-enhancer designed to increase the radiotherapy energy dose deposition inside tumor cells. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving NBTXR3 and radiation therapy may increase radiation-dependent tumor cell killing without increasing the radiation exposure of healthy surrounding tissues.