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

NCT02446444 | Active Not Recruiting Phase 3 DMC

• 2 other identifiers: ANZUP1303ACTRN12614000126617
• Study Type: interventional
• Target: 802
• Locations: 8 countries
• Sites: 68

Brief 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.

Conditions

Prostatic Neoplasms

Keywords

High risk; clinically localised prostate cancer

Outcome Measures

Primary Outcomes (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

  5 years

Secondary Outcomes (9)

• Overall survival

  5 years

• Prostate cancer-specific survival

  5 years

• PSA (Prostate-Specific Antigen) progression-free survival

  5 years

• Clinical progression-free survival

  5 years

• Time to subsequent hormonal therapy

  5 years

Study Arms (2)

Enzalutamide

EXPERIMENTAL

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)

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 COMPARATOR

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)

Drug: Conventional NSAA; Drug: LHRHA; Radiation: External Beam Radiotherapy (78 Gy in 39 fractions or 46 Gy in 23 fractions plus brachytherapy boost)

Interventions

Enzalutamide DRUG

Enzalutamide

Conventional NSAA DRUG

Conventional Non-steroidal Anti-androgen (NSAA)

LHRHA DRUG

Conventional Non-steroidal Anti-androgen (NSAA); Enzalutamide

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

Conventional Non-steroidal Anti-androgen (NSAA); Enzalutamide

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• 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
• 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.

Sponsors & Collaborators

• University of Sydney: lead
• Australian and New Zealand Urogenital and Prostate Cancer Trials Group: collaborator
• National Health and Medical Research Council, Australia: collaborator
• Cancer Trials Ireland: collaborator
• Trans Tasman Radiation Oncology Group: collaborator
• European Organisation for Research and Treatment of Cancer - EORTC: collaborator

Study Sites (69)

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Blacktown Hospital

Blacktown, New South Wales, 2148, Australia

Location

Campbelltown Hospital

Campbelltown, New South Wales, 2560, Australia

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Genesis Cancer Care Newcastle

Gateshead, New South Wales, 2290, Australia

Location

Gosford Hospital

Gosford, New South Wales, 2250, Australia

Location

St George Hospital

Kogarah, New South Wales, 2217, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Orange Health Service

Orange, New South Wales, 2800, Australia

Location

Prince of Wales Hospital

Randwick, New South Wales, 2131, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

St Vincent's Hospital

Sydney, New South Wales, 2010, Australia

Location

Tamworth Rural Referral Hospital

Tamworth, New South Wales, 2340, Australia

Location

Sydney Adventist Hospital

Wahroonga, New South Wales, 2076, Australia

Location

Calvary Mater Newcastle

Waratah, New South Wales, 2298, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Wollongong Hospital

Wollongong, New South Wales, 2500, Australia

Location

Genesis Cancer Care Queensland - Wesley and Chermside

Auchenflower, Queensland, 4066, Australia

Location

Townsville Hospital

Douglas, Queensland, 4814, Australia

Location

Royal Brisbane & Womens Hospital

Herston, Queensland, 4006, Australia

Location

Nambour General Hospital

Nambour, Queensland, 4560, Australia

Location

Radiation Oncology Services Mater Centre

South Brisbane, Queensland, 4101, Australia

Location

ICON - Gold Coast (formerly ROC Gold Coast)

Southport, Queensland, 4215, Australia

Location

ICON - Toowoomba (formerly ROC Toowoomba)

Toowoomba, Queensland, 4350, Australia

Location

Genesis Cancer Care Queensland - Tugun and Southport

Tugun, Queensland, 4224, Australia

Location

Princess Alexandra Hospital Brisbane

Woolloongabba, Queensland, 4102, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Ashford Cancer Centre Research (Adelaide Cancer Centre)

Kurralta Park, South Australia, 5037, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

Peter MacCallum Cancer Centre

Bendigo, Victoria, 3550, Australia

Location

Peter MacCallum Cancer Centre (Moorabbin Campus)

Bentleigh East, Victoria, 3165, Australia

Location

Eastern Health (Box Hill Hospital)

Box Hill, Victoria, 3128, Australia

Location

Genesis Care - Epping (formerly EROC)

Epping, Victoria, 3076, Australia

Location

Genesis Care - Western (formerly WROC)

Footscray, Victoria, 3011, Australia

Location

Genesis Care - Frankston (formerly FROC)

Frankston, Victoria, 3199, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3002, Australia

Location

Epworth HealthCare - Richmond

Richmond, Victoria, 3121, Australia

Location

Genesis Care - Ringwood (formerly RROC)

Ringwood East, Victoria, 3135, Australia

Location

Sunshine Hospital

St Albans, Victoria, 3021, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6149, Australia

Location

Salzburger Landeskliniken - Universitätsklinikum Salzburg

Salzburg, 5020, Austria

Location

AZ Groeninge Kortrijk- Campus Kennedylaan

Kortrijk, 8500, Belgium

Location

Cork University Hospital

Cork, Co Cork, Ireland

Location

Galway University Hospital

Galway, Co Galway, Ireland

Location

Mater Misericordiae University Hospital

Dublin, Dublin 7, Dublin 7, Ireland

Location

Beacon Private Hospital

Dublin, Dublin 18, Ireland

Location

St Luke's Hospital

Dublin, Dublin 6, Ireland

Location

Mater Private Hospital

Dublin, Dublin 7, Ireland

Location

Auckland City Hospital

Auckland, 1142, New Zealand

Location

Christchurch Hospital

Christchurch, 4170, New Zealand

Location

Palmerston North Hospital

Palmerston North, 4442, New Zealand

Location

The Institute Of Oncology

Ljubljana, 1000, Slovenia

Location

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

Badalona, Barcelona, 08916, Spain

Location

Hospital Donostia

Donostia / San Sebastian, Gipuzkoa, 20014, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Velindre Hospital

Whitchurch, Cardiff, CF14 2TL, United Kingdom

Location

University Hospital Southhampton

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Kent and Canterbury Hospital

Canterbury, Kent, CT1 3NG, United Kingdom

Location

Royal Marsden Hospital

Chelsea, London, SW3 6JJ, United Kingdom

Location

Western General Hospital

Edinburgh, Scotland, EH4 2XU, United Kingdom

Location

Royal United Hospital Bath

Bath, BA1 3NG, United Kingdom

Location

Addenbrookes Hospital

Cambridge, United Kingdom

Location

University of London Hospital

London, NW1 2BU, United Kingdom

Location

Guys and St Thomas Hospital

London, SE1 9RT, United Kingdom

Location

Charring Cross Hospital: Imperial College Healthcare NHS Trust

London, W6 8RF, United Kingdom

Location

Nottingham City Hospital- City Campus

Nottingham, NG5 1PB, United Kingdom

Location

Related Links

• Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group.
• University of Sydney, National Health and Medical Research Council (NHMRC) Clinical Trials Centre.
• Australian New Zealand Clinical Trials Registry (ANZCTR)

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Scott Williams

  ANZUP and Peter MacCallum Cancer Centre

  STUDY CHAIR

• Paul Nguyen

  Dana Farber Cancer Institute and ANZUP

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: May 4, 2015
• First Posted: May 18, 2015
• Study Start: March 1, 2014
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

ES (3); BE (1); GB (11); SL (1); AU (41); IE (6); NZ (3); US (2)