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


Condition: Prostatic Neoplasms

Intervention:

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

Purpose: 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.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02446444

Sponsor: University of Sydney

Primary Outcome Measures:

  • Measure: Overall survival time
  • Time Frame: 5 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Cause-specific survival time
  • Time Frame: 5 years
  • Safety Issue:
  • Measure: Prostate Specific Antigen (PSA) progression free survival time
  • Time Frame: 5 years
  • Safety Issue:
  • Measure: Clinical progression free survival time
  • Time Frame: 5 years
  • Safety Issue:
  • Measure: Time to subsequent hormonal therapy (restarting ADT)
  • Time Frame: 5 years
  • Safety Issue:
  • Measure: Time to castration-resistant disease (PCWG2 criteria)
  • Time Frame: 5 years
  • Safety Issue:
  • Measure: Metastasis-free survival (MFS)
  • Time Frame: 5 years
  • Safety Issue:
  • Measure: Adverse events (CTCAE v4.03)
  • Time Frame: 5 years
  • Safety Issue:
  • Measure: Health-related quality of life (EORTC Core Quality of Life Questionnaire (QLQC-30), Quality of Life Questionnaire for Prostate Cancer (PR-25), Euroqol 5 item preference-based measure of health (EQ-5 D-5L))
  • Time Frame: 5 years
  • Safety Issue:
  • Measure: Health outcomes relative to costs (incremental cost effectiveness ratio)
  • Time Frame: 5 years
  • Safety Issue:

Estimated Enrollment: 800

Study Start Date: March 2014

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

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, 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) 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

Contact:

  • ENZARAD Trial Coordinator
  • 02 9562 5368

Locations:

  • Dana Farber Cancer Institute
  • Boston Massachusetts 02115 United States
  • Beth Israel Deaconness Medical Center
  • Boston Massachusetts 02215 United States
  • Beth Israel Deaconness Medical Center
  • Boston Massachusetts 02215 United States
  • Blacktown Hospital
  • Blacktown New South Wales 2148 Australia
  • Campbelltown Hospital
  • Campbelltown New South Wales 2560 Australia
  • Chris O'Brien Lifehouse
  • Camperdown New South Wales 2050 Australia
  • Genesis Cancer Care Newcastle
  • Gateshead New South Wales 2290 Australia
  • Gosford Hospital
  • Gosford New South Wales 2250 Australia
  • St George Hospital
  • Kogarah New South Wales 2217 Australia
  • Liverpool Hospital
  • Liverpool New South Wales 2170 Australia
  • Central West Cancer Services
  • Orange New South Wales 2800 Australia
  • Prince of Wales Hospital
  • Randwick New South Wales 2131 Australia
  • Royal North Shore Hospital
  • St Leonards New South Wales 2065 Australia
  • St Vincent's Hospital
  • Sydney New South Wales 2010 Australia
  • Tamworth Rural Referral Hospital
  • Tamworth New South Wales 2340 Australia
  • Sydney Adventist Hospital
  • Wahroonga New South Wales 2076 Australia
  • Calvary Mater Newcastle
  • Waratah New South Wales 2298 Australia
  • Westmead Hospital
  • Westmead New South Wales 2145 Australia
  • Wollongong Hospital
  • Wollongong New South Wales 2500 Australia
  • Genesis Cancer Care Queensland - Wesley and Chermside
  • Auchenflower Queensland 4066 Australia
  • Townsville Hospital
  • Douglas Queensland 4814 Australia
  • Royal Brisbane & Womens Hospital
  • Herston Queensland 4006 Australia
  • Nambour General Hospital
  • Nambour Queensland 4560 Australia
  • Radiation Oncology Mater Centre
  • South Brisbane Queensland 4101 Australia
  • Radiation Oncology Centre- Gold Coast
  • Southport Queensland 4215 Australia
  • Oncology Research Australia
  • Toowoomba Queensland 4350 Australia
  • Genesis Cancer Care Queensland - Tugun and Southport
  • Tugun Queensland 4224 Australia
  • Princess Alexandra Hospital Brisbane
  • Woolloongabba Queensland 4102 Australia
  • Royal Adelaide Hospital
  • Adelaide South Australia 5000 Australia
  • Flinders Medical Centre
  • Bedford Park South Australia 5042 Australia
  • Ashford Cancer Care Research (Adelaide Cancer Centre)
  • Kurralta Park South Australia 5037 Australia
  • Royal Hobart Hospital
  • Hobart Tasmania 7000 Australia
  • Peter MacCallum Cancer Centre
  • Bendigo Victoria 3550 Australia
  • Peter MacCallum Cancer Centre (Moorabbin Campus)
  • Bentleigh East Victoria 3165 Australia
  • Eastern Health (Box Hill Hospital)
  • Box Hill Victoria 3128 Australia
  • Epping Radiation Oncology Centre
  • Epping Victoria 3076 Australia
  • Western Radiation Oncology Centre
  • Footscray Victoria 3011 Australia
  • Frankston Radiation Oncology Centre
  • Frankston Victoria 3199 Australia
  • Austin Health
  • Heidelberg Victoria 3084 Australia
  • Peter MacCallum Cancer Centre
  • Melbourne Victoria 3002 Australia
  • Epworth HealthCare - Richmond
  • Richmond Victoria 3121 Australia
  • Ringwood Radiation Oncology Centre
  • Ringwood East Victoria 3135 Australia
  • Sunshine Hospital
  • St Albans Victoria 3021 Australia
  • Fiona Stanley Hospital
  • Murdoch Western Australia 6149 Australia
  • Salzburger Landeskliniken - Universitätsklinikum Salzburg
  • Salzburg 5020 Austria
  • AZ Groeninge Kortrijk- Campus Kennedylaan
  • Kortrijk 8500 Belgium
  • Cork University Hospital
  • Cork Co Cork Ireland
  • Galway University Hospital
  • Galway Co Galway Ireland
  • Mater Misericordiae University Hospital
  • Dublin Dublin 7 Dublin 7 Ireland
  • Beacon Private Hospital
  • Dublin Dublin 18 Ireland
  • Mater Private Hospital
  • Dublin Dublin 7 Ireland
  • Auckland City Hospital
  • Auckland 1142 New Zealand
  • Christchurch Hospital
  • Christchurch 4170 New Zealand
  • Palmerston North Hospital
  • Palmerston North 4442 New Zealand
  • The Institute Of Oncology
  • Ljubljana 1000 Slovenia
  • Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)
  • Badalona Barcelona 08916 Spain
  • Hospital Donostia
  • Donostia Gipuzkoa 20014 Spain
  • Hospital Universitario de Salamanca
  • Salamanca 37007 Spain
  • Velindre Hospital
  • Whitchurch Cardiff CF14 2TL United Kingdom
  • University Hospital Southhampton
  • Southampton Hampshire SO16 6YD United Kingdom
  • St Luke's Hospital
  • Dublin Ireland Dublin 6 United Kingdom
  • Kent and Canterbury Hospital
  • Canterbury Kent CT1 3NG United Kingdom
  • Royal Marsden Hospital
  • Chelsea London SW3 6JJ United Kingdom
  • Western General Hospital
  • Edinburgh Scotland EH4 2XU United Kingdom
  • Royal United Hospital Bath
  • Bath BA1 3NG United Kingdom
  • Addenbrookes Hospital
  • Cambridge United Kingdom
  • University of London Hospital
  • London NW1 2BU United Kingdom
  • Guys and St Thomas Hospital
  • London SE1 9RT United Kingdom
  • Charring Cross Hospital: Imperial College Healthcare NHS Trust
  • London W6 8RF United Kingdom
  • Nottingham City Hospital- City Campus
  • Nottingham NG5 1PB United Kingdom

View trial on ClinicalTrials.gov


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