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)

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

doi:10.1111/bju.15384

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)

BJU Int. 2021 Sep;128(3):331-342. doi: 10.1111/bju.15384. Epub 2021 Apr 21.

Authors

Nattakorn Dhiantravan^{1

2

3}, Louise Emmett^{4

5

6}, Anthony M Joshua^{5

6

7}, David A Pattison^{8

9}, Roslyn J Francis^{10

11

12}, Scott Williams^{2

3

6

13}, Shahneen Sandhu^{2

3

6

14}, Ian D Davis^{6

15

16}, Ian Vela^{17

18}, Nitika Neha¹⁹, Mathias Bressel¹⁹, Declan G Murphy^{2

3

20}, Michael S Hofman^{1

2

3

6}, Arun A Azad^{2

3

6

14}

Affiliations

¹ Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
² Prostate Cancer Theranostics and Imaging Centre of Excellence (ProsTIC), Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
³ Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
⁴ Department of Theranostics, St Vincent's Hospital, Sydney, NSW, Australia.
⁵ Garvan Institute of Medical Research, Sydney, NSW, Australia.
⁶ Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group, Sydney, NSW, Australia.
⁷ Department of Medical Oncology, The Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, NSW, Australia.
⁸ Department of Nuclear Medicine & Specialised PET Services, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia.
⁹ School of Medicine, University of Queensland, Brisbane, QLD, Australia.
¹⁰ Department of Nuclear Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia.
¹¹ Medical School, University of Western Australia, Perth, WA, Australia.
¹² The Australasian Radiopharmaceutical Trial network (ARTnet), Sydney, NSW, Australia.
¹³ Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
¹⁴ Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
¹⁵ Eastern Health, Melbourne, VIC, Australia.
¹⁶ Eastern Health Clinical School, Monash University, Melbourne, VIC, Australia.
¹⁷ Department of Urology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia.
¹⁸ Prostate Cancer Research Centre-Queensland, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, Australia.
¹⁹ Centre for Biostatistics and Clinical Trials (BaCT), Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
²⁰ Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

PMID: 33682320
DOI: 10.1111/bju.15384

Abstract

Objective: To assess the activity and safety of sequential lutetium-177 (¹⁷⁷ Lu)-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. ⁶⁸ Ga-PSMA-11 and ¹⁸ F-FDG positron-emission tomography (PET)/CT undergo central review to determine eligibility. Patients are randomized 1:1 to experimental treatment, Arm A (¹⁷⁷ Lu-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 ¹⁷⁷ Lu-PSMA-617 in men with de novo mHNPC in a randomized phase 2 design.

Keywords: #PCSM; #ProstateCancer; #uroonc; PSMA; docetaxel; hormonal-naïve; prostate cancer; theranostics.

Publication types

Clinical Trial Protocol
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Antineoplastic Agents / administration & dosage*
Antineoplastic Agents, Hormonal
Clinical Trials, Phase II as Topic*
Docetaxel / administration & dosage*
Humans
Lutetium / administration & dosage*
Male
Multicenter Studies as Topic
Prostate-Specific Antigen / administration & dosage*
Prostatic Neoplasms / diagnostic imaging*
Prostatic Neoplasms / drug therapy*
Radiopharmaceuticals / administration & dosage*
Randomized Controlled Trials as Topic*
Research Design*

Substances

177Lu-PSMA-617
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Radiopharmaceuticals
Docetaxel
Lutetium
Prostate-Specific Antigen