TheraP: A randomized phase II trial of [177Lu]-PSMA-617 theranostic versus cabazitaxel in progressive metastatic castration-resistant prostate cancer.

Abstract

TPS332 Background: Lutetium-177 [177Lu]-PSMA-617 is a novel radiolabelled small molecule that binds with high affinity to prostate-specific membrane antigen (PSMA), which is commonly overexpressed in prostate cancer. This treatment has demonstrated promising activity and tolerability in men progressing after multiple lines of chemotherapy and endocrine therapy. This trial will determine the activity and safety of 177Lu-PSMA-617 compared to cabazitaxel chemotherapy in men with progressive metastatic castrate resistant prostate cancer. Methods: TheraP is an open-label, randomised, two-arm, multi-centre, phase 2 trial comparing the activity and safety of experimental treatment with [177Lu]-PSMA-617 versus standard 2nd line chemotherapy with cabazitaxel. Key eligibility criteria include prior chemotherapy with docetaxel; rising serum PSA; sufficient PSMA avidity according to central reviewed of imaging with PSMA PET/CT and FDG PET/CT; no discordance between FDG PET and PSMA PET. The trial will include 200 participants randomised in a 1:1 ratio to either [177Lu]-PSMA-617 intravenously every 6 weeks, 8.5 GBq for cycle 1, decreasing by 0.5 GBq with each subsequent cycle, up to maximum 6 cycles (experimental group); or, chemotherapy with cabazitaxel (20 mg/m2) intravenously every 3 weeks, for 10 cycles (standard group). In the event of an exceptional response to [177Lu]-PSMA-617, according to centrally-reviewed, post-therapy SPECT imaging, treatment is suspended but can recommence subsequently on progression. The primary endpoint is a 50% or greater reduction from baseline in serum PSA. Secondary endpoints include overall survival, progression-free survival (PFS), PSA-PFS, pain-PFS, radiographic-PFS, health-related quality of life, pain response, and adverse events. The outcomes of patients excluded because of discordant disease on FDG PET and PSMA PET will be reported as a tertiary objective. The study has accrued 79 of 200 planned participants from 29 January 2018 to 23 October 2018. Clinical trial information: NCT03392428.