UpFrontPSMA: a randomized phase 2 study of sequential ¹⁷⁷ Lu?PSMA?617 and docetaxel vs docetaxel in metastatic hormone?naïve prostate cancer (clinical trial protocol)

Objective To assess the activity and safety of sequential lutetium-177 (177Lu)-PSMA-617 docetaxel vs on a background androgen deprivation therapy (ADT) in men with de novo metastatic hormone-naïve prostate cancer (mHNPC). Patients Methods UpFrontPSMA (NCT04343885) is an open-label, randomized, multicentre, phase 2 trial, recruiting 140 patients at 12 Australian centres. Key eligibility criteria include: histological diagnosis within weeks screening commencement; prostate-specific antigen (PSA) >10 ng/mL diagnosis; ?4 ADT; evidence disease computed tomography (CT) and/or bone scan; high-volume membrane (PSMA)-avid maximum standardized uptake value >15; absence extensive discordant fluorodeoxyglcuose (FDG)-positive, PSMA-negative disease. 68Ga-PSMA-11 18F-FDG positron-emission (PET)/CT undergo central review to determine eligibility. are randomized 1:1 experimental treatment, Arm A (177Lu-PSMA-617 7.5GBq q6w × cycles followed by 75 mg/m2 q3w 6 cycles), or standard-of-care B (docetaxel cycles). All receive continuous ADT. stratified based volume conventional imaging duration ADT time registration. The primary endpoint proportion undetectable PSA (?0.2 ng/L) months after study treatment commencement. Secondary endpoints include safety, castration resistance, overall survival, radiographic progression-free objective tumour response rate, early PSMA PET response, health-related quality life, frequency severity adverse events. Enrolment commenced April 2020. Results Conclusions results this trial will generate data 177Lu-PSMA-617 mHNPC design.