TY - JOUR
T1 - ENZA-p trial protocol
T2 - a randomized phase II trial using prostate-specific membrane antigen as a therapeutic target and prognostic indicator in men with metastatic castration-resistant prostate cancer treated with enzalutamide (ANZUP 1901)
AU - Emmett, Louise
AU - Subramaniam, Shalini
AU - Joshua, Anthony M.
AU - Crumbaker, Megan
AU - Martin, Andrew
AU - Zhang, Alison Y.
AU - Rana, Nisha
AU - Langford, Ailsa
AU - Mitchell, Jenna
AU - Yip, Sonia
AU - Francis, Roslyn
AU - Hofman, Michael S.
AU - Sandhu, Shahneen
AU - Azad, Arun
AU - Gedye, Craig
AU - McJannett, Margaret
AU - Stockler, Martin R.
AU - Davis, Ian D.
AU - on behalf of the Australian, New Zealand Urogenital, Prostate Cancer Trials Group (ANZUP), the ENZA-p investigators
N1 - Funding Information:
Louise Emmett reports personal fees from AstraZeneca, Mundipharma, Janssen and Astellas, outside the submitted work. Anthony M. Joshua reports other from Astellas, outside the submitted work. Alison Y. Zhang reports grants and personal fees from Astellas, outside the submitted work. Michael S. Hofman reports grants from Movember, the Medical Research Future Fund (MRFF), Endocyte, a Novartis Company, during the conduct of the study; grants from Prostate Cancer Foundation Australia, Movember, the US Department of Defence, Peter MacCallum Foundation, personal fees from Janssen, personal fees from Sanofi Genzyme, personal fees from Mundipharma, personal fees from Astellas, and personal fees from Merck/MSD, outside the submitted work. Arun Azad reports personal fees, non‐financial support and other from Janssen, grants, personal fees, non‐financial support and other from Astellas, grants, personal fees, non‐financial support and other from Novartis, grants, personal fees, non‐financial support and other from Merck Serono, personal fees, non‐financial support and other from Tolmar, personal fees, non‐financial support and other from Amgen, grants, personal fees, non‐financial support and other from Pfizer, personal fees and other from Bayer, personal fees and other from Telix Pharmaceuticals, grants, personal fees and other from Bristol‐Myers Squibb, grants, personal fees and other from Sanofi, personal fees and other from Noxopharm, grants, personal fees and other from Astra Zeneca, grants from Glaxo Smith Kline, grants from Aptevo Therapeutics, grants from MedImmune, grants from Bionomics, grants from SYNthorx, grants, personal fees and other from Ipsen, and personal fees and other from Merck Sharpe & Dohme outside the submitted work. Margaret McJannett reports grants from Movember, grants from Endocyte, a Novartis Company, GenesisCare, grants from St Vincent’s Clinic Foundation, drug support from Astellas, and philanthropic donation from Roy Morgan during the conduct of the study. Craig Gedye reports grants from BMS, Ipsen, MSD, Amgen (all grants to institutions, no salary or personal income accepted), personal fees from Astellas, Astra Zeneca, MSD, EMD Serono, Ipsen, Pfizer, BMS, Janssen (no honorarium or speakers fees accepted; donated directly to 3rd party not‐for‐profit), non‐financial support from Astellas, BMS, MSD (travel support for conferences in lieu of public employment contract entitlements), outside the submitted work. Martin R. Stockler reports grants from Astellas, Amgen, Astra Zeneca, Bayer, Bionomics, Bristol‐Myers Squibb, Celgene, Medivation, Merck Sharp & Dohme, Pfizer, Roche, Sanofi and Tilray outside the submitted work. Ian D. Davis reports grants from the NHMRC during the conduct of the study, other from Pfizer, ANZUP Cancer Trials Group, Bayer, Astellas, Janssen, Movember Foundation and Merck Sharp & Dohme, outside the submitted work, and is the unremunerated chair of the ANZUP Cancer Trials Group. The remaining authors have nothing to disclose. 18 68 177
Publisher Copyright:
© 2021 The Authors BJU International © 2021 BJU International
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/11
Y1 - 2021/11
N2 - Objectives: To determine the activity and safety of lutetium-177 (177Lu)-prostate-specific membrane antigen (PSMA)-617 in men with metastatic castration-resistant prostate cancer (mCRPC) commencing enzalutamide, who are at high risk of early progression, and to identify potential prognostic and predictive biomarkers from imaging, blood and tissue. Participants and Methods: ENZA-p (ANZUP 1901) is an open-label, randomized, two-arm, multicentre, phase 2 trial. Participants are randomly assigned (1:1) to treatment with enzalutamide 160 mg daily alone or enzalutamide plus 177Lu-PSMA-617 7.5 GBq on Days 15 and 57. Two additional 177Lu-PSMA-617 doses are allowed, informed by Day-92 Gallium-68 (68Ga)-PSMA positron emission tomography (PET; up to four doses in total). The primary endpoint is prostate-specific antigen (PSA) progression-free survival (PFS). Other major endpoints include radiological PFS, PSA response rate, overall survival, health-related quality of life, adverse events and cost-effectiveness. Key eligibility criteria include: biochemical and/or clinical progression; 68Ga-PSMA PET-avid disease; no prior androgen signalling inhibitor, excepting abiraterone; no prior chemotherapy for mCRPC; and ≥2 high-risk features for early enzalutamide failure. Assessments are 4 weekly during study treatment, then 6 weekly until radiographic progression. Response Evaluation Criteria in Solid Tumours (RECIST) are used to assess imaging conducted every 12 weeks, 68Ga-PSMA PET at baseline, Days 15 and 92, and at progression, and 18F-fluorine deoxyglucose (18F-FDG) PET at baseline and progression. Translational samples include blood (and optional biopsies) at baseline, Day 92, and first progression. Correlative studies include identification of prognostic and predictive biomarkers from 68Ga-PSMA and 18F-FDG PET/CT, circulating tumour cells and circulating tumour DNA. The trial will enrol 160 participants, providing 80% power with a two-sided type-1 error rate of 5% to detect a hazard ratio of 0.625 assuming a median PSA-PFS of 5 months with enzalutamide alone. Results and Conclusion: The combination of 177Lu-PSMA-617 and enzalutamide may be synergistic. ENZA-p will determine the safety and efficacy of the combination in addition to developing predictive and prognostic biomarkers to better guide treatment decisions.
AB - Objectives: To determine the activity and safety of lutetium-177 (177Lu)-prostate-specific membrane antigen (PSMA)-617 in men with metastatic castration-resistant prostate cancer (mCRPC) commencing enzalutamide, who are at high risk of early progression, and to identify potential prognostic and predictive biomarkers from imaging, blood and tissue. Participants and Methods: ENZA-p (ANZUP 1901) is an open-label, randomized, two-arm, multicentre, phase 2 trial. Participants are randomly assigned (1:1) to treatment with enzalutamide 160 mg daily alone or enzalutamide plus 177Lu-PSMA-617 7.5 GBq on Days 15 and 57. Two additional 177Lu-PSMA-617 doses are allowed, informed by Day-92 Gallium-68 (68Ga)-PSMA positron emission tomography (PET; up to four doses in total). The primary endpoint is prostate-specific antigen (PSA) progression-free survival (PFS). Other major endpoints include radiological PFS, PSA response rate, overall survival, health-related quality of life, adverse events and cost-effectiveness. Key eligibility criteria include: biochemical and/or clinical progression; 68Ga-PSMA PET-avid disease; no prior androgen signalling inhibitor, excepting abiraterone; no prior chemotherapy for mCRPC; and ≥2 high-risk features for early enzalutamide failure. Assessments are 4 weekly during study treatment, then 6 weekly until radiographic progression. Response Evaluation Criteria in Solid Tumours (RECIST) are used to assess imaging conducted every 12 weeks, 68Ga-PSMA PET at baseline, Days 15 and 92, and at progression, and 18F-fluorine deoxyglucose (18F-FDG) PET at baseline and progression. Translational samples include blood (and optional biopsies) at baseline, Day 92, and first progression. Correlative studies include identification of prognostic and predictive biomarkers from 68Ga-PSMA and 18F-FDG PET/CT, circulating tumour cells and circulating tumour DNA. The trial will enrol 160 participants, providing 80% power with a two-sided type-1 error rate of 5% to detect a hazard ratio of 0.625 assuming a median PSA-PFS of 5 months with enzalutamide alone. Results and Conclusion: The combination of 177Lu-PSMA-617 and enzalutamide may be synergistic. ENZA-p will determine the safety and efficacy of the combination in addition to developing predictive and prognostic biomarkers to better guide treatment decisions.
KW - castration-resistant
KW - clinical trial
KW - enzalutamide
KW - prostate cancer
KW - PSMA
KW - theranostics
UR - http://www.scopus.com/inward/record.url?scp=85109184856&partnerID=8YFLogxK
U2 - 10.1111/bju.15491
DO - 10.1111/bju.15491
M3 - Article
C2 - 34028967
AN - SCOPUS:85109184856
SN - 1464-4096
VL - 128
SP - 642
EP - 651
JO - BJU International
JF - BJU International
IS - 5
ER -
