This is a Phase 1/2 prospective, open-label, two cohorts, non-randomized trial consisting of two consecutive steps, a dose escalation and a subsequent dose expansion part.~PART 1 DOSE ESCALATION: subjects with newly diagnosed Unfavorable Intermediate~Risk (UIR) or High Risk (HR) prostate adenocarcinoma, will participate in a dose escalation of NBTXR3 activated by two different radiation schedules. NBTXR3 will be administered by intra-prostate injection and then activated 10 days later either by:~EBRT delivered as 45 Gy in 25 fractions of 1.8 Gy each; to the prostate and seminal vesicles, followed by 34.2 Gy in 19 fractions to the prostate and proximal seminal vesicles, over 9-10 weeks, utilizing intensity modulated radiotherapy (IMRT) with daily image guidance aligned to implanted fiducial markers (COHORT A) or,~Brachytherapy Boost and EBRT delivered as a single fraction of 15 Gy in one day to the prostate by High Dose Rate Brachytherapy followed by EBRT (initiated within 2-4 weeks after completion of Brachytherapy), delivered as 45 Gy in 25 fractions of 1.8 Gy to the prostate and seminal vesicles utilizing intensity modulated radiotherapy (IMRT) with daily image guidance aligned to implanted fiducial markers (COHORT B)~PART 2 DOSE EXPANSION: Two parallel cohorts of subjects, A and B, 20 subjects per cohort, will be treated at either the RD1 (Recommended Dose of NBTXR3 given as intraprostate injection and activated by EBRT) or RD2 (Recommended Dose of NBTXR3 given as intra-prostate injection and activated by Brachytherapy Boost and EBRT), as determined in the Phase I dose escalation of the trial.~All subjects will receive androgen deprivation therapy (ADT) LHRH / GnRH agonist beginning 8 weeks before the NBTXR3 administration and for 24 months in subjects with (HR) prostate adenocarcinoma. The duration of ADT in subjects with (UIR) disease will be of 6 months.~Subjects will receive a single intra-prostate injection of NBTXR3 which will be delivered to the prostate via transperineal injection under TRUS guidance injection. NBTXR3 injection will be performed on Day 1 and will be assessed for safety, intra-prostate availability and presence of NBTXR3 in the peripheral circulation.~COHORT A: External beam radiation therapy will be delivered to the prostate starting within 9 days after the NBTXR3 injection (Day 10). Total dose of 79.2 Gy, delivered as 25 fractions of 1.8 Gy to the prostate and seminal vesicles (45 Gy), followed by 34.2 Gy in 19 fractions to the prostate and proximal seminal vesicles, delivered over 9-10 weeks, utilizing intensity modulated radiotherapy (IMRT) with daily image guidance aligned to implanted fiducial markers COHORT B: HDR Brachytherapy implantation will be performed within 9 days after NBTXR3 injection (Day 10). Brachytherapy Boost delivered as a single fraction of 15 Gy in one day to the prostate by High Dose Rate Brachytherapy followed by EBRT (initiated within 2-4 weeks after completion of Brachytherapy) delivered as 45 Gy in 25 fractions of 1.8 Gy to the prostate and seminal vesicles utilizing intensity modulated radiotherapy (IMRT) with daily image guidance aligned to implanted fiducial markers.~Subjects will be followed for safety assessment until the end of the study. Before the onset of study treatment, subjects must have a histologic diagnosis of either Unfavorable Intermediate Risk (UIR) or High Risk (HR) prostate adenocarcinoma.
This study is a Phase 1/2 open-label involving 2 groups of patients newly diagnosed with either unfavorable intermediate risk or high risk prostate adenocarcinoma. One group will receive only EBRT and the other group will receive a Brachytherapy boost and EBRT. Both groups will receive treatment with androgen deprivation. There will be 2 consecutive steps, a dose escalation and a subsequent dose expansion part.