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Prostatic NeoplasmsPhase 3ENZAMETNCT02446405

Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer

A Phase 3 study testing Enzalutamide, NSAA and LHRHA or Surgical Castration in people with Prostatic Neoplasms, run by University of Sydney at 82 sites in 6 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostatic Neoplasms
What is being tested?
Enzalutamide, NSAA and LHRHA or Surgical Castration
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,125 participants
Where
82 sitesin 6 countries
Study dates
Mar 2014to 30 Jun 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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.
Show all 16Show fewer
  • 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
  • Human Immunodeficiency Virus (HIV)-infection is not an exclusion criterion if it is controlled with anti-retroviral drugs that are unaffected by concomitant enzalutamide.
  • 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.

Trial locations and contacts

82 sites in 6 countries.

82 sites in 6 countries

Australia38 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Flinders Medical Centre

    Bedford Park, South Australia, 5042

  • Bendigo Hospital

    Bendigo, Victoria

  • Monash Cancer Centre Moorabbin

    Bentleigh East, Victoria, 3165

  • Sunshine Coast University Hospital

    Birtinya, Queensland, 4575

  • Chris O'Brien Lifehouse

    Camperdown, New South Wales, 2050

  • Coffs Harbour Health Campus

    Coffs Harbour, New South Wales, 2450

  • Concord Cancer Centre - Concord Repatriation General Hospital

    Concord, New South Wales, 2139

  • St Vincent's Hospital Sydney

    Darlinghurst, New South Wales, 2010

  • Townsville Hospital

    Douglas, Queensland, 4814

  • Peter MacCallum Cancer Centre - East Melbourne

    East Melbourne, Victoria, 3002

  • St. Vincents Hospital Melbourne

    Fitzroy, Victoria, 3065

  • Peninsula South Eastern Haematology & Oncology Group- Peninsula Oncology Centre

    Frankston, Victoria, 3199

  • University Hospital Geelong

    Geelong, Victoria, 3220

  • Austin Hospital

    Heidelberg, Victoria, 3084

  • Royal Brisbane and Women's Hospital

    Herston, Queensland, 4006

  • Royal Hobart Hospital

    Hobart, Tasmania, 7000

  • Nepean Cancer Care Centre

    Kingswood, New South Wales, 2747

  • St. George Hospital

    Kogarah, New South Wales, 2217

  • Adelaide Cancer Centre - Ashford Cancer Care Centre

    Kurralta Park, South Australia, 5037

  • Australian Urology Associates

    Malvern, Victoria, 3144

  • Eastern Health Box Hill Hospital

    Melbourne, Victoria

  • Sir Charles Gairdner Hospital

    Nedlands, Western Australia, 6009

  • Central West Cancer Services

    Orange, New South Wales, 2800

  • Fiona Stanley Hospital (formerly Royal Perth Hospital)

    Perth, Western Australia, 6000

  • Port Macquarie Base Hospital

    Port Macquarie, New South Wales, 2444

  • Prince of Wales Hospital

    Randwick, New South Wales, 2031

  • Goulburn Valley Health

    Shepparton, Victoria, 3630

  • Gold Coast University Hospital

    Southport, Queensland, 4215

  • Genesis Care North Shore

    St Leonards, New South Wales, 2065

  • Tamworth Rural Referral Hospital

    Tamworth, New South Wales, 2340

  • Royal Darwin Hospital

    Tiwi, Northern Territory, 0810

  • The Tweed Hospital

    Tweed Heads, New South Wales, 2485

  • Riverina Cancer Care Centre

    Wagga Wagga, New South Wales, 2650

  • Sydney Adventist Hospital

    Wahroonga, New South Wales, 2076

  • Border Medical Oncology

    Wodonga, Victoria, 3690

  • Wollongong Hospital

    Wollongong, New South Wales, 2500

  • Princess Alexandra Hospital

    Woolloongabba, Queensland, 4102

Other trials in Australia

Canada21 sites

  • Prostate Cancer Institute - Southern Alberta Institute of Urology

    Calgary, Alberta, T2V 1P9

  • Cambridge Memorial Hospital

    Cambridge, Ontario, ON N1R 7S6

  • Cross Cancer Institute

    Edmonton, Alberta, AB T6G 1Z2

  • Horizon Health Network - Dr Everett Chalmers Hospital

    Fredericton, New Brunswick, NB E3B 5N5

  • QEII Health Sciences Centre, Capital District Health Authority

    Halifax, Nova Scotia, NS B3H 2Y9

  • Juravinski Cancer Centre

    Hamilton, Ontario, L8V 5C2

  • Cancer Centre of Southeastern Ontario at Kingston General Hospital

    Kingston, Ontario, ON K7L 5P9

  • London Regional Cancer Program

    London, Ontario, N6A 5W9

  • Hôpital Notre-Dame

    Montreal, Quebec, H2L 4M1

  • Lakeridge Health Oshawa

    Oshawa, Ontario, ON L1G 2B9

  • Ottawa Hospital Cancer Centre

    Ottawa, Ontario, ON K1H 8L6

  • CHUQ-Pavillon Hotel-Dieu de Quebec

    Québec, Quebec, QC G1R 2J6

  • Allan Blair Cancer Centre

    Regina, Saskatchewan, S4T 7T1

  • Saint John Regional Hospital

    Saint John, New Brunswick, NB E2L 4L4

  • Saskatoon Cancer Centre

    Saskatoon, Saskatchewan, S7N 4H4

  • Algoma District Cancer Program Sault Area Hospital

    Sault Ste. Marie, Ontario, P6B 0A8

  • BCCA - Fraser Valley Cancer Center

    Surrey, British Columbia, BC V3V 1Z2

  • Thunder Bay Regional Health Sciences Centre

    Thunder Bay, Ontario, ON P7B 6V4

  • University Health Network - Princess Margaret Hospital

    Toronto, Ontario, ON M5G 2M9

  • BCCA Vancouver Centre

    Vancouver, British Columbia, V5Z 4E6

  • CancerCare Manitoba

    Winnipeg, Manitoba

Other trials in Canada

United Kingdom10 sites

  • Aberdeen Royal Infirmary

    Aberdeen, Scotland, AB25 2ZN

  • Royal Sussex Hospital

    Brighton, East Sussex, BN2 5BE

  • Kent and Canterbury Hospital

    Canterbury, Kent, CT1 3NG

  • Velindre Cancer Centre

    Cardiff, Wales, CF14 2TL

  • University College Hospital London

    London, NW1 2BU

  • Guys and St Thomas Hospital

    London, SE1 9RT

  • Royal Marsden Hospital

    London, SW3 6JJ

  • University Hospital Southampton

    Southampton, SO16 6YD

  • Great Western Hospital

    Swindon, SN3 6BB

  • Royal Cornwall Hospital

    Truro, Cornwall, TR1 3LQ

Other trials in United Kingdom

Ireland9 sites

  • Beaumont Hospital

    Beaumont, Dublin, Dublin 9

  • Beacon Private Hospital

    Dublin, Dublin 18

  • St Vincent's University Hospital

    Dublin, Dublin 4

  • Mater Misercordiae University Hospital

    Dublin, Dublin 7

  • Mater Private Hospital

    Dublin, Dublin 7

  • St James Hospital

    Dublin, Dublin 8

  • Galway University Hospital

    Galway

  • Adelaide and Meath Hospital - National Children's Hospital

    Tallaght, Dublin 24

  • University Hospital Waterford

    Waterford

Other trials in Ireland

New Zealand3 sites

  • Auckland City Hospital

    Auckland

  • Christchurch Hospital

    Christchurch, 8140

  • Waikato Hospital

    Hamilton, 3204

Other trials in New Zealand

United States1 site

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: Randomised Phase 3 Trial of Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer: ENZAMET

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.

Being tested
Enzalutamide, NSAA, LHRHA or Surgical Castration
Keywords
metastatic prostate cancer, prostate cancer, prostate cancer treatment, enzalutamide
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02446405
Study groupRoleWhat they receive
EnzalutamideExperimentalEnzalutamide 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.
Receives: Drug: Enzalutamide; Drug: LHRHA or Surgical Castration
Conventional NSAAActive 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.
Receives: Drug: NSAA; Drug: LHRHA or Surgical Castration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival Time

    the interval from the date of randomisation to date of death.

    Measured: 3 years

Secondary outcomes (5)

  1. Prostate specific antigen progression free survival time

    the interval from the date of randomisation to the date of first evidence of PSA progression, clinical progression, or death from any cause, whichever occurs first, or the date of last known follow-up without PSA progression

    PSA progression is defined as: a rise in PSA by more than 25% AND more than 2ng/mL

    Measured: 3 years

  2. Clinical progression free survival time

    the interval from the date of randomisation to the date of first clinical evidence of disease progression or death from any cause, whichever occurs first, or the date of last known follow-up without clinical progression

    Measured: 3 years

  3. Adverse events

    The NCI Common Terminology Criteria for Adverse Events version 4 (CTCAE v4.03) will be used to classify and grade the intensity of adverse events during study treatment

    Measured: 3 years

  4. 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))

    HRQL will be reported by participants using the EORTC core quality of life questionnaire (QLQ C-30) and prostate cancer specific module (PR-25). The EQ-5D-5L will be used to derive utility scores suitable for quality adjusted survival analyses

    Measured: 3 years

  5. Healthcare resource cost-effectiveness (incremental cost effectiveness ratio)

    Information on the following areas of health-care resource usage will be collected: hospitalisations, visits to health professionals, and medications Australian unit costs will be applied to the resource usage data to estimate the incremental cost of the addition of enzalutamide to standard treatment

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 May 2015 (estimated)
  2. Study startMar 2014
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion30 Jun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Stratification factors: 1. High volume disease (yes versus no), characterised as: * 4 or more bone metastases, one of which is outside the vertebral column and pelvis AND/OR * Visceral metastases (e.g. lung, pleura, liver, adrenal and others) Lymph node involvement or bladder invasion do NOT qualify as visceral disease. 2. Study site 3. Concomitant "anti-resorptive" therapy to delay skeletal related events when commencing ADT 4. Co-morbidities according to the Adult Co-morbidity Evaluation (ACE-27: 0-1 vs 2-3) 5. Early use of docetaxel defined as use of docetaxel in conjunction with initiation of ADT.
Masking
None (open label)
Enrolment
1,125 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02446405
Sponsor's protocol ID
ANZUP 1304
Other IDs
ACTRN12614000110684
Acronym
ENZAMET
Status last verified
Feb 2025
First submitted
4 May 2015
Last updated
6 Feb 2025
Results posted
No
Data monitoring committee
Yes

Publications

  • Law CK, Stockler MR, Martin AJ, Davis ID, Sweeney CJ, Morton RL. Cost-effectiveness of adding enzalutamide vs standard non-steroidal antiandrogen drugs for patients with metastatic hormone-sensitive prostate cancer undergoing standard first-line therapy: a within-trial, secondary end-point analysis of the ENZAMET phase 3, international randomized trial (ANZUP 1304). EClinicalMedicine. 2026 Oct 5;100:104207. doi: 10.1016/j.eclinm.2026.104207. eCollection 2026 Oct.

    PubMed 42890411

  • 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.

    PubMed 39404227

  • Sweeney 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.

    PubMed 36990608

  • Stockler 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.

    PubMed 34928708

  • Davis 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.

    PubMed 31157964

  • Davis 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.

    PubMed 29525541

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Enzalutamide, NSAA and LHRHA or Surgical Castration in people with Prostatic Neoplasms, run by University of Sydney at 82 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 6 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 82 sites in Australia, Canada, United Kingdom, Ireland, New Zealand and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival Time (time frame: 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02446405, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2025.

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