NCT03253744 is a phase I trial with the primary objective to identify the maximally tolerated dose (MTD) of salvage stereotactic body radiotherapy (SBRT) in patients with local prostate cancer recurrence after brachytherapy. Additional objectives included biochemical control and imaging response.

This trial was initially designed to test three therapeutic dose levels (DLs): 40Gy (DL1), 42.5Gy (DL2), and 45Gy (DL3) in 5 fractions. Intensity modulation was utilized to deliver the prescription dose to the MRI and PSMA-based PET imaging-defined gross tumor volume while simultaneously delivering 30Gy to an elective volume defined by the prostate gland. This phase I trial followed a 3+3 design with a 3-patient expansion at the maximum tolerated dose (MTD). Toxicities were scored until trial completion at two years post-SBRT utilizing CTCAE v5.0 criteria. Escalation was halted if two dose limiting toxicities (DLTs) occurred, defined as any persistent (>4 days) grade (G) 3 toxicity occurring within the first 3 weeks after SBRT or any ≥G3 GU or G4 GI toxicity thereafter.

Between 08/2018 and 01/2023, 9 patients underwent salvage SBRT and were observed for a median of 22 months (Q1-Q3,20-43 months). No grade 3-5 AEs related to study treatment were observed, and, thus, no DLTs occurred during the observation period. Escalation was halted by amendment given excellent biochemical control in DL1 and DL2 in the setting of a high incidence of clinically significant late G2 GU toxicity. Therefore, the MTD was considered 42.5Gy in 5 fractions (DL2). One- and two-year biochemical progression free survival (bPFS) were 100% and 86% representing a single patient in the trial cohort with biochemical failure (PSA nadir+2.0) at 20 months post-treatment.

The MTD of salvage SBRT for the treatment of intraprostatic radiorecurrence after brachytherapy was considered to be 42.5Gy in 5 fractions producing an 86% 2-year bPFS, with one post-study failure at 20 months. The most frequent clinically significant toxicity was late G2 GU toxicity.