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

Nattakorn Dhiantravan, Louise Emmett, Anthony M. Joshua, David A. Pattison, Roslyn J. Francis, Scott Williams, Shahneen Sandhu, Ian D. Davis, Ian Vela, Nitika Neha, Mathias Bressel, Declan G. Murphy, Michael S. Hofman, Arun A. Azad

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)331-342
Number of pages12
JournalBJU International
Volume128
Issue number3
Early online date7 Mar 2021
DOIs
Publication statusPublished - Sept 2021

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