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Prostatic NeoplasmsPhase 3ENZARADNCT02446444

Enzalutamide in Androgen Deprivation Therapy With Radiation Therapy for High Risk, Clinically Localised, Prostate Cancer

A Phase 3 study testing Enzalutamide, Conventional NSAA and LHRHA in people with Prostatic Neoplasms, run by University of Sydney at 69 sites in 9 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 as part of adjuvant androgen deprivation therapy (ADT) with a luteinizing hormone releasing hormone analogue (LHRHA) in men having radiation therapy for localised prostate cancer at high risk of recurrence. 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, Conventional NSAA and LHRHA
Could I receive a placebo?
No, everyone receives an active treatment
How many people
802 participants
Where
69 sitesin 9 countries
Study dates
Mar 2014to Jun 2026
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

  • Pathological diagnosis of adenocarcinoma of the prostate, judged to be at high risk for recurrence based on any of the following (in accordance with the International Society of Urological Pathology (ISUP) Consensus 2005:
  • Gleason score 8-10 OR Gleason score of 4+3 AND clinical T2b-4 AND PSA >20ng/mL OR N1 disease (involvement of lymph nodes at or below the bifurcation of the common iliac arteries) defined radiologically as greater than 10mm on short axis using standard CT or MRI, or biopsy proven
  • Age ≥18 years
  • 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 ULN and bilirubin < 1.5 x Upper Limit of Normal (ULN), (or if bilirubin is between 1.5 - 2 x ULN, they must have a normal conjugated bilirubin).
  • Adequate renal function: calculated creatinine clearance > 30 ml/min (Cockcroft-Gault)
Show all 11Show fewer
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Study treatment both planned and able to start within 7 days of randomisation.
  • Willing and able to comply with all study requirements, including treatment, and attending required assessments
  • Has completed the baseline HRQOL questionnaires UNLESS is unable to complete because of literacy or limited vision
  • Signed, written, informed consent

Who cannot join

  • Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components
  • Involvement of lymph nodes superior to the common iliac bifurcation, and/or outside the pelvis (distant lymph nodes). Lymph node involvement is defined by histopathological confirmation, or by a short axis measurement >10mm on standard imaging (CT or MRI, but not PET).
  • Any contraindication to external beam radiotherapy
  • 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
Show all 21Show fewer
  • significant cardiovascular disease within the last 3 months: including myocardial infarction, unstable angina, congestive heart failure (NYHA grade II or greater), ongoing arrhythmias of Grade > 2 , thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism). Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.
  • Evidence of metastatic disease: minimum imaging required Computed tomography scan (CT) / Magnetic Resonance Imaging (MRI) of the abdomen and pelvis, and Whole Body Bone Scan (WBBS). If equivocal bone scan, follow-up plain films are required to show NO evidence of cancer if not covered by CT/MRI
  • PSA > 100 ng/mL
  • History of another malignancy within 5 years prior to randomisation except for non-melanomatous carcinoma of the skin; or, adequately treated, non-muscle-invasive urothelial carcinoma of the bladder (i.e. 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.
  • Use of hormonal therapy or androgen deprivation therapy, including enzalutamide, except in the following setting:
  • Use of LHRHA (with or without anti-androgens) for less than 30 days prior to randomisation in the trial.
  • Bilateral orchidectomy or radical prostatectomy
  • Prior brachytherapy or other radiotherapy that would result in an overlap of radiotherapy fields
  • Participation in other clinical trials of investigational agents for the treatment of prostate cancer or other diseases.
  • Major surgery within 21 days prior to randomisation
  • Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of enzalutamide, including difficulty swallowing tablets

Trial locations and contacts

69 sites in 9 countries.

69 sites in 9 countries

Australia41 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Genesis Cancer Care Queensland - Wesley and Chermside

    Auchenflower, Queensland, 4066

  • Flinders Medical Centre

    Bedford Park, South Australia, 5042

  • Peter MacCallum Cancer Centre

    Bendigo, Victoria, 3550

  • Peter MacCallum Cancer Centre (Moorabbin Campus)

    Bentleigh East, Victoria, 3165

  • Blacktown Hospital

    Blacktown, New South Wales, 2148

  • Eastern Health (Box Hill Hospital)

    Box Hill, Victoria, 3128

  • Campbelltown Hospital

    Campbelltown, New South Wales, 2560

  • Chris O'Brien Lifehouse

    Camperdown, New South Wales, 2050

  • Townsville Hospital

    Douglas, Queensland, 4814

  • Genesis Care - Epping (formerly EROC)

    Epping, Victoria, 3076

  • Genesis Care - Western (formerly WROC)

    Footscray, Victoria, 3011

  • Genesis Care - Frankston (formerly FROC)

    Frankston, Victoria, 3199

  • Genesis Cancer Care Newcastle

    Gateshead, New South Wales, 2290

  • Gosford Hospital

    Gosford, New South Wales, 2250

  • Austin Health

    Heidelberg, Victoria, 3084

  • Royal Brisbane & Womens Hospital

    Herston, Queensland, 4006

  • Royal Hobart Hospital

    Hobart, Tasmania, 7000

  • St George Hospital

    Kogarah, New South Wales, 2217

  • Ashford Cancer Centre Research (Adelaide Cancer Centre)

    Kurralta Park, South Australia, 5037

  • Liverpool Hospital

    Liverpool, New South Wales, 2170

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3002

  • Fiona Stanley Hospital

    Murdoch, Western Australia, 6149

  • Nambour General Hospital

    Nambour, Queensland, 4560

  • Orange Health Service

    Orange, New South Wales, 2800

  • Prince of Wales Hospital

    Randwick, New South Wales, 2131

  • Epworth HealthCare - Richmond

    Richmond, Victoria, 3121

  • Genesis Care - Ringwood (formerly RROC)

    Ringwood East, Victoria, 3135

  • Radiation Oncology Services Mater Centre

    South Brisbane, Queensland, 4101

  • ICON - Gold Coast (formerly ROC Gold Coast)

    Southport, Queensland, 4215

  • Sunshine Hospital

    St Albans, Victoria, 3021

  • Royal North Shore Hospital

    St Leonards, New South Wales, 2065

  • St Vincent's Hospital

    Sydney, New South Wales, 2010

  • Tamworth Rural Referral Hospital

    Tamworth, New South Wales, 2340

  • ICON - Toowoomba (formerly ROC Toowoomba)

    Toowoomba, Queensland, 4350

  • Genesis Cancer Care Queensland - Tugun and Southport

    Tugun, Queensland, 4224

  • Sydney Adventist Hospital

    Wahroonga, New South Wales, 2076

  • Calvary Mater Newcastle

    Waratah, New South Wales, 2298

  • Westmead Hospital

    Westmead, New South Wales, 2145

  • Wollongong Hospital

    Wollongong, New South Wales, 2500

  • Princess Alexandra Hospital Brisbane

    Woolloongabba, Queensland, 4102

Other trials in Australia

United Kingdom11 sites

  • Royal United Hospital Bath

    Bath, BA1 3NG

  • Addenbrookes Hospital

    Cambridge

  • Kent and Canterbury Hospital

    Canterbury, Kent, CT1 3NG

  • Royal Marsden Hospital

    Chelsea, London, SW3 6JJ

  • Western General Hospital

    Edinburgh, Scotland, EH4 2XU

  • University of London Hospital

    London, NW1 2BU

  • Guys and St Thomas Hospital

    London, SE1 9RT

  • Charring Cross Hospital: Imperial College Healthcare NHS Trust

    London, W6 8RF

  • Nottingham City Hospital- City Campus

    Nottingham, NG5 1PB

  • University Hospital Southhampton

    Southampton, Hampshire, SO16 6YD

  • Velindre Hospital

    Whitchurch, Cardiff, CF14 2TL

Other trials in United Kingdom

Ireland6 sites

  • Cork University Hospital

    Cork, Co Cork

  • Mater Misericordiae University Hospital

    Dublin, Dublin 7, Dublin 7

  • Beacon Private Hospital

    Dublin, Dublin 18

  • St Luke's Hospital

    Dublin, Dublin 6

  • Mater Private Hospital

    Dublin, Dublin 7

  • Galway University Hospital

    Galway, Co Galway

Other trials in Ireland

New Zealand3 sites

  • Auckland City Hospital

    Auckland, 1142

  • Christchurch Hospital

    Christchurch, 4170

  • Palmerston North Hospital

    Palmerston North, 4442

Other trials in New Zealand

Spain3 sites

  • Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)

    Badalona, Barcelona, 08916

  • Hospital Donostia

    Donostia / San Sebastian, Gipuzkoa, 20014

  • Hospital Universitario de Salamanca

    Salamanca, 37007

Other trials in Spain

United States2 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

Other trials in United States

Austria1 site

  • Salzburger Landeskliniken - Universitätsklinikum Salzburg

    Salzburg, 5020

Other trials in Austria

Belgium1 site

  • AZ Groeninge Kortrijk- Campus Kennedylaan

    Kortrijk, 8500

Other trials in Belgium

Slovenia1 site

  • The Institute Of Oncology

    Ljubljana, 1000

Other trials in Slovenia

About this study

Official title: Randomised Phase 3 Trial of Enzalutamide in Androgen Deprivation Therapy With Radiation Therapy for High Risk, Clinically Localised, Prostate Cancer: ENZARAD

The purpose of this study is to determine the effectiveness of enzalutamide as part of adjuvant androgen deprivation therapy (ADT) with a luteinizing hormone releasing hormone analogue (LHRHA) in men having radiation therapy for localised prostate cancer at high risk of recurrence.

Being tested
Enzalutamide, Conventional NSAA, LHRHA, External Beam Radiotherapy (78 Gy in 39 fractions or 46 Gy in 23 fractions plus brachytherapy boost)
Keywords
High risk, clinically localised prostate cancer
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • EnzalutamideDrug

  • Conventional NSAADrug

  • LHRHADrug

  • External Beam Radiotherapy (78 Gy in 39 fractions or 46 Gy in 23 fractions plus brachytherapy boost)Radiation

Study groups in NCT02446444
Study groupRoleWhat they receive
EnzalutamideExperimentalEnzalutamide 160 mg daily, by mouth, for 24 months from randomisation. All participants are treated with a LHRHA for 24 months from randomisation and external beam radiation therapy started approximately 16 weeks after randomisation (+/- brachytherapy boost)
Receives: Drug: Enzalutamide; Drug: LHRHA; Radiation: External Beam Radiotherapy (78 Gy in 39 fractions or 46 Gy in 23 fractions plus brachytherapy boost)
Conventional Non-steroidal Anti-androgen (NSAA)Active comparatorConventional Non-steroidal Anti-androgen (NSAA), by mouth, for 6 months from randomisation. All participants are treated with a LHRHA for 24 months from randomisation and external beam radiation therapy started approximately 16 weeks after randomisation (+/- brachytherapy boost)
Receives: Drug: Conventional NSAA; Drug: LHRHA; Radiation: External Beam Radiotherapy (78 Gy in 39 fractions or 46 Gy in 23 fractions plus brachytherapy boost)

What is being measured

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

  1. Metastasis-free survival

    Metastasis free survival (MFS) is defined as the interval from the date of randomisation to the date of first evidence of metastasis or death from any cause, whichever occurs first, or the date of last known follow-up alive and without metastases.

    Evidence of metastasis includes findings on whole body bone scan (WBBS) or CT or MRI that are either characteristic of metastatic prostate cancer, and/or confirmed by other test results, e.g. cytology or histopathology, and lesion qualifies as new metastatic disease per RECIST 1.1. Detection of metastasis by other modalities, eg Ga-68 PSMA (Prostate Specific Membrane Antigen) PET, does not constitute an event unless confirmed by WBBS or CT or MR

    Measured: 5 years

Secondary outcomes (9)

  1. Overall survival

    Overall survival (OS) is defined as the interval from the date of randomisation to date of death from any cause, or the date of last known follow-up alive.

    Measured: 5 years

  2. Prostate cancer-specific survival

    Prostate cancer-specific survival is defined as the interval from the date of randomisation to the date of death from prostate cancer, or the date of last known follow-up alive.

    Measured: 5 years

  3. PSA (Prostate-Specific Antigen) progression-free survival

    PSA progression-free survival is defined as 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 and without clinical progression.

    PSA progression as defined by the Phoenix criteria: an increase in PSA of more than 2ng/mL above the nadir (lowest) PSA level.

    Measured: 5 years

  4. Clinical progression-free survival

    Clinical progression-free survival is defined as 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 alive without clinical progression.

    Clinical evidence of disease progression includes evidence of progression or recurrence on imaging, clinical examination, development of symptoms attributable to cancer progression, or initiation of other anticancer treatment for prostate cancer.

    Measured: 5 years

  5. Time to subsequent hormonal therapy

    Time to subsequent hormone therapy is the interval from randomisation to the first date that androgen deprivation therapy is recommenced for the treatment of recurrent (or progressive) prostate cancer, or the date of last known follow-up without recommencement of androgen deprivation therapy.

    Measured: 5 years

  6. Time to castration-resistant disease (PCWG2 criteria)

    Castration resistant prostate cancer (CRPC) is defined, per PCWG2, by a rising PSA that is greater than 2ng/mL higher than the most recent nadir with a testosterone < 50 ng/dL (<1.7 nmol/L); the rise has to be at least 25% over the most recent nadir; and, the rise has to be confirmed by a second PSA at least three weeks later. The time to castration-resistant prostate cancer is defined as the interval from randomisation to the date that the PSA first met the criteria defined above (i.e. the date of the first PSA to meet these criteria, not the date of the subsequent confirmatory test), or the date of last known follow-up without CRPC.

    Measured: 5 years

  7. Safety (adverse events - CTCAE v4.03)

    The NCI Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03) will be used to classify and grade the intensity of adverse events occurring until 30 days after the last dose of study treatment.

    Measured: 5 years

  8. Health related quality of life (HRQL)

    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: 5 years

  9. Health outcomes relative to costs (incremental cost effectiveness ratio)

    Information on the following areas of health-care resource usage will be collected: hospitalisations, visits to health professionals, and medications. Quality-adjusted survival (QAS) time will be used to quantify the incremental effectiveness of adding enzalutamide to standard treatment.

    Measured: 5 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 completionJun 2026 (estimated)
  4. Study completionJun 2026 (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: * Gleason score (\<=7 versus 8-10), * Regional lymph nodes involvement (N0 versus N1) * Clinical T-stage (T2 and below versus T3 and above), * PSA (\<20ng/mL versus ≥ 20ng/mL) * Study Site * Brachytherapy (yes versus no) * Pelvic Field (yes versus no)
Masking
None (open label)
Enrolment
802 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02446444
Sponsor's protocol ID
ANZUP1303
Other IDs
ACTRN12614000126617
Acronym
ENZARAD
Status last verified
May 2026
First submitted
4 May 2015
Last updated
6 May 2026
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Enzalutamide, Conventional NSAA and LHRHA in people with Prostatic Neoplasms, run by University of Sydney at 69 sites in 9 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 11 inclusion and 21 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 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 69 sites in Australia, United Kingdom, Ireland, New Zealand, Spain and 4 more countries. 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?

Metastasis-free survival (time frame: 5 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 NCT02446444.

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 May 2026; AzTrials last refreshed its copy on 26 Oct 2026.

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