Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer
ENZAMET
Randomised Phase 3 Trial of Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer: ENZAMET
2 other identifiers
interventional
1,125
6 countries
82
Brief Summary
The purpose of this study is to determine the effectiveness of enzalutamide, versus a conventional non-steroidal anti androgen (NSAA), when combined with a luteinizing hormone releasing hormone analog (LHRHA) or surgical castration, as first line androgen deprivation therapy (ADT) for newly diagnosed metastatic prostate cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Mar 2014
Longer than P75 for phase_3
82 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2014
CompletedFirst Submitted
Initial submission to the registry
May 4, 2015
CompletedFirst Posted
Study publicly available on registry
May 18, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2027
February 6, 2025
February 1, 2025
12.8 years
May 4, 2015
February 3, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Survival Time
the interval from the date of randomisation to date of death.
3 years
Secondary Outcomes (5)
Prostate specific antigen progression free survival time
3 years
Clinical progression free survival time
3 years
Adverse events
3 years
Health-related quality of life (EORTC Core Quality of Life Questionnaire (QLQ C-30), Quality of Life Questionnaire for Prostate Cancer (PR-25), Euroqol 5 item preference-based measure of health (EQ-5 D-5L))
3 years
Healthcare resource cost-effectiveness (incremental cost effectiveness ratio)
3 years
Study Arms (2)
Enzalutamide
EXPERIMENTALEnzalutamide is 160 mg daily, by mouth, until clinical disease progression or prohibitive toxicity. All participants are to receive standard background therapy with a LHRHA or surgical castration, as per standard of care. The choice of the LHRHA or surgical castration is at the discretion of the treating clinician.
Conventional NSAA
ACTIVE COMPARATORConventional NSAA, by mouth until clinical disease progression or prohibitive toxicity. All participants are to receive standard background therapy with a LHRHA or surgical castration, as per standard of care. The choice of the LHRHA or surgical castration is at the discretion of the treating clinician.
Interventions
Eligibility Criteria
You may qualify if:
- Male aged 18 or older with metastatic adenocarcinoma of the prostate
- Target or non-target lesions according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1
- Adequate bone marrow function: Haemoglobin (Hb) ≥100g/L and White Cell Count (WCC) ≥ 4.0 x 109/L and platelets ≥100 x 109/L.
- Adequate liver function: Alanine transaminase (ALT) \< 2 x Upper Limit of Normal (ULN) and bilirubin \< 1.5 x ULN, (or if bilirubin is between 1.5-2 x ULN, they must have a normal conjugated bilirubin). If liver metastases are present ALT must be \< 5 x ULN
- Adequate renal function: calculated creatinine clearance \> 30 ml/min (Cockcroft-Gault)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Patients with performance status 2 are only eligible if the decline in performance status is due to metastatic prostate cancer.
- Study treatment both planned and able to start within 7 days after randomisation.
- Willing and able to comply with all study requirements, including treatment and required assessments
- Has completed baseline Health-Related Quality of Life (HRQL) questionnaires UNLESS is unable to complete because of limited literacy or vision
- Signed, written, informed consent
You may not qualify if:
- Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components
- History of
- seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma).
- loss of consciousness or transient ischemic attack within 12 months of randomization
- significant cardiovascular disease within the last 3 months including: myocardial infarction, unstable angina, congestive heart failure, ongoing arrhythmias of Grade \>2 \[National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.03\], thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism). Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.
- Life expectancy of less than 12 months.
- History of another malignancy within 5 years prior to randomisation, except for either non- melanomatous carcinoma of the skin or, adequately treated, non-muscle-invasive urothelial carcinoma of the bladder (Tis, Ta and low grade T1 tumours).
- Concurrent illness, including severe infection that might jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
- Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse;
- Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception.
- Prior ADT for prostate cancer (including bilateral orchidectomy), except in the following settings:
- Started less than 12 weeks prior to randomisation AND Prostate Specific Antigen (PSA) is stable or falling. The 12 weeks starts from whichever of the following occurs earliest: first dose of oral anti- androgen, LHRHA, or surgical castration.
- In the adjuvant setting, where the completion of adjuvant hormonal therapy was more than 12 months prior to randomisation AND the total duration of hormonal treatment did not exceed 24 months. For depot preparations, hormonal therapy is deemed to have started with the first dose and to have been completed when the next dose would otherwise have been due, e.g. 12 weeks after the last dose of depot goserelin 10.8mg.
- Prior cytotoxic chemotherapy for prostate cancer, but up to 2 cycles of docetaxel chemotherapy for metastatic disease is permitted.
- Participation in other clinical trials of investigational agents for the treatment of prostate cancer or other diseases.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Sydneylead
- Australian and New Zealand Urogenital and Prostate Cancer Trials Groupcollaborator
- Cancer Trials Irelandcollaborator
- Canadian Cancer Trials Groupcollaborator
- Astellas Pharma Inccollaborator
Study Sites (82)
Dana Farber Cancer Institute
Boston, Massachusetts, 02115, United States
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050, Australia
Coffs Harbour Health Campus
Coffs Harbour, New South Wales, 2450, Australia
Concord Cancer Centre - Concord Repatriation General Hospital
Concord, New South Wales, 2139, Australia
St Vincent's Hospital Sydney
Darlinghurst, New South Wales, 2010, Australia
Nepean Cancer Care Centre
Kingswood, New South Wales, 2747, Australia
St. George Hospital
Kogarah, New South Wales, 2217, Australia
Central West Cancer Services
Orange, New South Wales, 2800, Australia
Port Macquarie Base Hospital
Port Macquarie, New South Wales, 2444, Australia
Prince of Wales Hospital
Randwick, New South Wales, 2031, Australia
Genesis Care North Shore
St Leonards, New South Wales, 2065, Australia
Tamworth Rural Referral Hospital
Tamworth, New South Wales, 2340, Australia
The Tweed Hospital
Tweed Heads, New South Wales, 2485, Australia
Riverina Cancer Care Centre
Wagga Wagga, New South Wales, 2650, Australia
Sydney Adventist Hospital
Wahroonga, New South Wales, 2076, Australia
Wollongong Hospital
Wollongong, New South Wales, 2500, Australia
Royal Darwin Hospital
Tiwi, Northern Territory, 0810, Australia
Sunshine Coast University Hospital
Birtinya, Queensland, 4575, Australia
Townsville Hospital
Douglas, Queensland, 4814, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, 4006, Australia
Gold Coast University Hospital
Southport, Queensland, 4215, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102, Australia
Royal Adelaide Hospital
Adelaide, South Australia, 5000, Australia
Flinders Medical Centre
Bedford Park, South Australia, 5042, Australia
Adelaide Cancer Centre - Ashford Cancer Care Centre
Kurralta Park, South Australia, 5037, Australia
Royal Hobart Hospital
Hobart, Tasmania, 7000, Australia
Bendigo Hospital
Bendigo, Victoria, Australia
Monash Cancer Centre Moorabbin
Bentleigh East, Victoria, 3165, Australia
Peter MacCallum Cancer Centre - East Melbourne
East Melbourne, Victoria, 3002, Australia
St. Vincents Hospital Melbourne
Fitzroy, Victoria, 3065, Australia
Peninsula South Eastern Haematology & Oncology Group- Peninsula Oncology Centre
Frankston, Victoria, 3199, Australia
University Hospital Geelong
Geelong, Victoria, 3220, Australia
Austin Hospital
Heidelberg, Victoria, 3084, Australia
Australian Urology Associates
Malvern, Victoria, 3144, Australia
Eastern Health Box Hill Hospital
Melbourne, Victoria, Australia
Goulburn Valley Health
Shepparton, Victoria, 3630, Australia
Border Medical Oncology
Wodonga, Victoria, 3690, Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, 6009, Australia
Fiona Stanley Hospital (formerly Royal Perth Hospital)
Perth, Western Australia, 6000, Australia
Prostate Cancer Institute - Southern Alberta Institute of Urology
Calgary, Alberta, T2V 1P9, Canada
Cross Cancer Institute
Edmonton, Alberta, AB T6G 1Z2, Canada
BCCA - Fraser Valley Cancer Center
Surrey, British Columbia, BC V3V 1Z2, Canada
BCCA Vancouver Centre
Vancouver, British Columbia, V5Z 4E6, Canada
CancerCare Manitoba
Winnipeg, Manitoba, Canada
Horizon Health Network - Dr Everett Chalmers Hospital
Fredericton, New Brunswick, NB E3B 5N5, Canada
Saint John Regional Hospital
Saint John, New Brunswick, NB E2L 4L4, Canada
QEII Health Sciences Centre, Capital District Health Authority
Halifax, Nova Scotia, NS B3H 2Y9, Canada
Cambridge Memorial Hospital
Cambridge, Ontario, ON N1R 7S6, Canada
Juravinski Cancer Centre
Hamilton, Ontario, L8V 5C2, Canada
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, ON K7L 5P9, Canada
London Regional Cancer Program
London, Ontario, N6A 5W9, Canada
Lakeridge Health Oshawa
Oshawa, Ontario, ON L1G 2B9, Canada
Ottawa Hospital Cancer Centre
Ottawa, Ontario, ON K1H 8L6, Canada
Algoma District Cancer Program Sault Area Hospital
Sault Ste. Marie, Ontario, P6B 0A8, Canada
Thunder Bay Regional Health Sciences Centre
Thunder Bay, Ontario, ON P7B 6V4, Canada
University Health Network - Princess Margaret Hospital
Toronto, Ontario, ON M5G 2M9, Canada
Hôpital Notre-Dame
Montreal, Quebec, H2L 4M1, Canada
CHUQ-Pavillon Hotel-Dieu de Quebec
Québec, Quebec, QC G1R 2J6, Canada
Allan Blair Cancer Centre
Regina, Saskatchewan, S4T 7T1, Canada
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, S7N 4H4, Canada
Beaumont Hospital
Beaumont, Dublin, Dublin 9, Ireland
Beacon Private Hospital
Dublin, Dublin 18, Ireland
St Vincent's University Hospital
Dublin, Dublin 4, Ireland
Mater Misercordiae University Hospital
Dublin, Dublin 7, Ireland
Mater Private Hospital
Dublin, Dublin 7, Ireland
St James Hospital
Dublin, Dublin 8, Ireland
Galway University Hospital
Galway, Ireland
Adelaide and Meath Hospital - National Children's Hospital
Tallaght, Dublin 24, Ireland
University Hospital Waterford
Waterford, Ireland
Auckland City Hospital
Auckland, New Zealand
Christchurch Hospital
Christchurch, 8140, New Zealand
Waikato Hospital
Hamilton, 3204, New Zealand
Royal Cornwall Hospital
Truro, Cornwall, TR1 3LQ, United Kingdom
Royal Sussex Hospital
Brighton, East Sussex, BN2 5BE, United Kingdom
Kent and Canterbury Hospital
Canterbury, Kent, CT1 3NG, United Kingdom
Aberdeen Royal Infirmary
Aberdeen, Scotland, AB25 2ZN, United Kingdom
Velindre Cancer Centre
Cardiff, Wales, CF14 2TL, United Kingdom
University College Hospital London
London, NW1 2BU, United Kingdom
Guys and St Thomas Hospital
London, SE1 9RT, United Kingdom
Royal Marsden Hospital
London, SW3 6JJ, United Kingdom
University Hospital Southampton
Southampton, SO16 6YD, United Kingdom
Great Western Hospital
Swindon, SN3 6BB, United Kingdom
Related Publications (5)
Armstrong AJ, Azad AA, Conduit C, Haas GP, Bland C, Davis ID. Enzalutamide in metastatic hormone-sensitive prostate cancer: A plain language summary of the ARCHES and ENZAMET follow-up studies. Future Oncol. 2025 Jan;21(1):15-24. doi: 10.1080/14796694.2024.2408101. Epub 2024 Oct 15.
PMID: 39404227DERIVEDSweeney CJ, Martin AJ, Stockler MR, Begbie S, Cheung L, Chi KN, Chowdhury S, Frydenberg M, Horvath LG, Joshua AM, Lawrence NJ, Marx G, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar W, Pook DW, Reaume MN, Sandhu SK, Tan A, Tan TH, Thomson A, Vera-Badillo F, Williams SG, Winter D, Yip S, Zhang AY, Zielinski RR, Davis ID; ENZAMET trial investigators and Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):323-334. doi: 10.1016/S1470-2045(23)00063-3.
PMID: 36990608DERIVEDStockler MR, Martin AJ, Davis ID, Dhillon HM, Begbie SD, Chi KN, Chowdhury S, Coskinas X, Frydenberg M, Hague WE, Horvath LG, Joshua AM, Lawrence NJ, Marx GM, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar WR, Pook DW, Reaume MN, Sandhu S, Tan A, Tan TH, Thomson A, Vera-Badillo F, Williams SG, Winter DG, Yip S, Zhang AY, Zielinski RR, Sweeney CJ; ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). Health-Related Quality of Life in Metastatic, Hormone-Sensitive Prostate Cancer: ENZAMET (ANZUP 1304), an International, Randomized Phase III Trial Led by ANZUP. J Clin Oncol. 2022 Mar 10;40(8):837-846. doi: 10.1200/JCO.21.00941. Epub 2021 Dec 20.
PMID: 34928708DERIVEDDavis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, Coskinas X, Frydenberg M, Hague WE, Horvath LG, Joshua AM, Lawrence NJ, Marx G, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar W, Pook DW, Reaume MN, Sandhu SK, Tan A, Tan TH, Thomson A, Tu E, Vera-Badillo F, Williams SG, Yip S, Zhang AY, Zielinski RR, Sweeney CJ; ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. N Engl J Med. 2019 Jul 11;381(2):121-131. doi: 10.1056/NEJMoa1903835. Epub 2019 Jun 2.
PMID: 31157964DERIVEDDavis ID. Answering Questions and Questioning Answers: More Evidence To Guide Decision-making About Chemohormonal Therapy in Metastatic Prostate Cancer. Eur Urol. 2018 Jun;73(6):856-858. doi: 10.1016/j.eururo.2018.02.020. Epub 2018 Mar 7. No abstract available.
PMID: 29525541DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Christopher Sweeney
Dana Farber Cancer Institute and ANZUP
- STUDY CHAIR
Ian Davis
ANZUP and Eastern Health Box Hill Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 4, 2015
First Posted
May 18, 2015
Study Start
March 1, 2014
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
June 30, 2027
Last Updated
February 6, 2025
Record last verified: 2025-02