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

NCT ID: NCT02446444

Last Updated: 2025-05-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

802 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-03-31

Study Completion Date

2026-03-31

Brief Summary

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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.

Detailed Description

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Conditions

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Prostatic Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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)
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Enzalutamide

Enzalutamide 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)

Group Type EXPERIMENTAL

Enzalutamide

Intervention Type DRUG

LHRHA

Intervention Type DRUG

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

Intervention Type RADIATION

Conventional Non-steroidal Anti-androgen (NSAA)

Conventional 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)

Group Type ACTIVE_COMPARATOR

Conventional NSAA

Intervention Type DRUG

LHRHA

Intervention Type DRUG

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

Intervention Type RADIATION

Interventions

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Enzalutamide

Intervention Type DRUG

Conventional NSAA

Intervention Type DRUG

LHRHA

Intervention Type DRUG

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

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

1. 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
2. Age ≥18 years
3. Adequate bone marrow function Haemoglobin (Hb) ≥100g/L and White Cell Count (WCC) ≥ 4.0 x 109/L and platelets ≥100 x 109/L
4. 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).
5. Adequate renal function: calculated creatinine clearance \> 30 ml/min (Cockcroft-Gault)
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
7. Study treatment both planned and able to start within 7 days of randomisation.
8. Willing and able to comply with all study requirements, including treatment, and attending required assessments
9. Has completed the baseline HRQOL questionnaires UNLESS is unable to complete because of literacy or limited vision
10. Signed, written, informed consent

Exclusion Criteria

1. Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components
2. 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).
3. Any contraindication to external beam radiotherapy
4. 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 (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.
5. 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
6. PSA \> 100 ng/mL
7. 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).
8. 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.
9. 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;
10. Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception.
11. 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.
12. Bilateral orchidectomy or radical prostatectomy
13. Prior brachytherapy or other radiotherapy that would result in an overlap of radiotherapy fields
14. Participation in other clinical trials of investigational agents for the treatment of prostate cancer or other diseases.
15. Major surgery within 21 days prior to randomisation
16. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of enzalutamide, including difficulty swallowing tablets
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Australian and New Zealand Urogenital and Prostate Cancer Trials Group

OTHER

Sponsor Role collaborator

National Health and Medical Research Council, Australia

OTHER

Sponsor Role collaborator

Cancer Trials Ireland

NETWORK

Sponsor Role collaborator

Trans Tasman Radiation Oncology Group

OTHER

Sponsor Role collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role collaborator

University of Sydney

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Scott Williams

Role: STUDY_CHAIR

ANZUP and Peter MacCallum Cancer Centre

Paul Nguyen

Role: STUDY_CHAIR

Dana Farber Cancer Institute and ANZUP

Locations

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Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Blacktown Hospital

Blacktown, New South Wales, Australia

Site Status

Campbelltown Hospital

Campbelltown, New South Wales, Australia

Site Status

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

Site Status

Genesis Cancer Care Newcastle

Gateshead, New South Wales, Australia

Site Status

Gosford Hospital

Gosford, New South Wales, Australia

Site Status

St George Hospital

Kogarah, New South Wales, Australia

Site Status

Liverpool Hospital

Liverpool, New South Wales, Australia

Site Status

Orange Health Service

Orange, New South Wales, Australia

Site Status

Prince of Wales Hospital

Randwick, New South Wales, Australia

Site Status

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Site Status

St Vincent's Hospital

Sydney, New South Wales, Australia

Site Status

Tamworth Rural Referral Hospital

Tamworth, New South Wales, Australia

Site Status

Sydney Adventist Hospital

Wahroonga, New South Wales, Australia

Site Status

Calvary Mater Newcastle

Waratah, New South Wales, Australia

Site Status

Westmead Hospital

Westmead, New South Wales, Australia

Site Status

Wollongong Hospital

Wollongong, New South Wales, Australia

Site Status

Genesis Cancer Care Queensland - Wesley and Chermside

Auchenflower, Queensland, Australia

Site Status

Townsville Hospital

Douglas, Queensland, Australia

Site Status

Royal Brisbane & Womens Hospital

Herston, Queensland, Australia

Site Status

Nambour General Hospital

Nambour, Queensland, Australia

Site Status

Radiation Oncology Services Mater Centre

South Brisbane, Queensland, Australia

Site Status

ICON - Gold Coast (formerly ROC Gold Coast)

Southport, Queensland, Australia

Site Status

ICON - Toowoomba (formerly ROC Toowoomba)

Toowoomba, Queensland, Australia

Site Status

Genesis Cancer Care Queensland - Tugun and Southport

Tugun, Queensland, Australia

Site Status

Princess Alexandra Hospital Brisbane

Woolloongabba, Queensland, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Flinders Medical Centre

Bedford Park, South Australia, Australia

Site Status

Ashford Cancer Centre Research (Adelaide Cancer Centre)

Kurralta Park, South Australia, Australia

Site Status

Royal Hobart Hospital

Hobart, Tasmania, Australia

Site Status

Peter MacCallum Cancer Centre

Bendigo, Victoria, Australia

Site Status

Peter MacCallum Cancer Centre (Moorabbin Campus)

Bentleigh East, Victoria, Australia

Site Status

Eastern Health (Box Hill Hospital)

Box Hill, Victoria, Australia

Site Status

Genesis Care - Epping (formerly EROC)

Epping, Victoria, Australia

Site Status

Genesis Care - Western (formerly WROC)

Footscray, Victoria, Australia

Site Status

Genesis Care - Frankston (formerly FROC)

Frankston, Victoria, Australia

Site Status

Austin Health

Heidelberg, Victoria, Australia

Site Status

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Site Status

Epworth HealthCare - Richmond

Richmond, Victoria, Australia

Site Status

Genesis Care - Ringwood (formerly RROC)

Ringwood East, Victoria, Australia

Site Status

Sunshine Hospital

St Albans, Victoria, Australia

Site Status

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Site Status

Salzburger Landeskliniken - Universitätsklinikum Salzburg

Salzburg, , Austria

Site Status

AZ Groeninge Kortrijk- Campus Kennedylaan

Kortrijk, , Belgium

Site Status

Cork University Hospital

Cork, Co Cork, Ireland

Site Status

Galway University Hospital

Galway, Co Galway, Ireland

Site Status

Mater Misericordiae University Hospital

Dublin, Dublin 7, Ireland

Site Status

Beacon Private Hospital

Dublin, , Ireland

Site Status

St Luke's Hospital

Dublin, , Ireland

Site Status

Mater Private Hospital

Dublin, , Ireland

Site Status

Auckland City Hospital

Auckland, , New Zealand

Site Status

Christchurch Hospital

Christchurch, , New Zealand

Site Status

Palmerston North Hospital

Palmerston North, , New Zealand

Site Status

The Institute Of Oncology

Ljubljana, , Slovenia

Site Status

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

Badalona, Barcelona, Spain

Site Status

Hospital Donostia

Donostia / San Sebastian, Gipuzkoa, Spain

Site Status

Hospital Universitario de Salamanca

Salamanca, , Spain

Site Status

Velindre Hospital

Whitchurch, Cardiff, United Kingdom

Site Status

University Hospital Southhampton

Southampton, Hampshire, United Kingdom

Site Status

Kent and Canterbury Hospital

Canterbury, Kent, United Kingdom

Site Status

Royal Marsden Hospital

Chelsea, London, United Kingdom

Site Status

Western General Hospital

Edinburgh, Scotland, United Kingdom

Site Status

Royal United Hospital Bath

Bath, , United Kingdom

Site Status

Addenbrookes Hospital

Cambridge, , United Kingdom

Site Status

University of London Hospital

London, , United Kingdom

Site Status

Guys and St Thomas Hospital

London, , United Kingdom

Site Status

Charring Cross Hospital: Imperial College Healthcare NHS Trust

London, , United Kingdom

Site Status

Nottingham City Hospital- City Campus

Nottingham, , United Kingdom

Site Status

Countries

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United States Australia Austria Belgium Ireland New Zealand Slovenia Spain United Kingdom

Related Links

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https://www.anzup.org.au

Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group.

http://ctc.usyd.edu.au/

University of Sydney, National Health and Medical Research Council (NHMRC) Clinical Trials Centre.

http://www.anzctr.org.au/

Australian New Zealand Clinical Trials Registry (ANZCTR)

Other Identifiers

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ACTRN12614000126617

Identifier Type: OTHER

Identifier Source: secondary_id

ANZUP1303

Identifier Type: -

Identifier Source: org_study_id

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