Randomised phase 3 trial of enzalutamide in androgen deprivation therapy with radiation therapy for high risk, clinically localised, prostate cancer: ENZARAD
- Conditions
- Localised prostate cancer at high risk of recurrence
- Registration Number
- 2024-514808-13-00
- Lead Sponsor
- Cancer Trials Ireland
- Brief Summary
To determine effects on Metastasis-free survival (metastasis or death from any cause, MFS)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing, recruitment ended
- Sex
- Male
- Target Recruitment
- 79
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 ISUP Consensus 2005 (16) see Appendix 3): 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.
Signed, written, informed consent
Age ≥ 18 yrs
Adequate bone marrow function: Hb ≥100g/L and WCC ≥ 4.0 x 109/L and platelets ≥100 x 109/L
Adequate liver function: ALT < 2 x ULN and bilirubin < 1.5 x 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 (Cockroft-Gault)
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 HRQL questionnaires UNLESS is unable to complete because of literacy or limited vision
Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components
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: a. 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
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 a. seizure or any condition that may predispose to seizure (e.g. prior cortical stroke or significant brain trauma). b. loss of consciousness or transient ischemic attack within 12 months of randomization. c. significant cardiovascular disease within the last 3 months:including myocardial infarction, unstable angina, congestive heart failure (NYHA grade II or greater, see Appendix 4), ongoing arrhythmias of Grade > 2 (NCI CTCAE, version 4.03) , 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 is a CT and/or MRI of the abdomen and pelvis, and a 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 a. 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;
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Metastasis-free survival (metastasis or death from any cause, MFS) Metastasis-free survival (metastasis or death from any cause, MFS)
- Secondary Outcome Measures
Name Time Method Overall survival (death from any cause, OS) Overall survival (death from any cause, OS)
Prostate cancer specific survival (death from prostate cancer) Prostate cancer specific survival (death from prostate cancer)
PSA progression-free survival (Phoenix criteria, or death from any cause, PSA-PFS) PSA progression-free survival (Phoenix criteria, or death from any cause, PSA-PFS)
Clinical progression-free survival (imaging, symptoms, signs, initiation of other anti-cancer treatment, or death from any cause, clinical-PFS) Clinical progression-free survival (imaging, symptoms, signs, initiation of other anti-cancer treatment, or death from any cause, clinical-PFS)
Time to subsequent hormonal therapy (restarting ADT) Time to subsequent hormonal therapy (restarting ADT)
Time to castration-resistant disease (PCWG2 criteria) Time to castration-resistant disease (PCWG2 criteria)
Safety (adverse events - CTCAE v4.03) Safety (adverse events - CTCAE v4.03)
Health related quality of life (EORTC QLQC-30 & PR-25, EQ-5D-5L) Health related quality of life (EORTC QLQC-30 & PR-25, EQ-5D-5L)
Health outcomes relative to costs (incremental cost effectiveness ration) Health outcomes relative to costs (incremental cost effectiveness ration)
Trial Locations
- Locations (8)
Gemeinnuetzige Salzburger Landeskliniken Betriebsgesellschaft mbH
🇦🇹Salzburg, Austria
University Hospital Galway
🇮🇪Galway, Ireland
Mater Private Hospital
🇮🇪Dublin 7, Ireland
Mater Misericordiae University Hospital
🇮🇪Dublin 7, Ireland
Saint Luke's Radiation Oncology Network
🇮🇪Dublin 6, Ireland
Cork University Hospital
🇮🇪Cork, Ireland
Beacon Hospital
🇮🇪Dublin 18, Ireland
Institut Catala D'oncologia
🇪🇸Badalona, Spain
Gemeinnuetzige Salzburger Landeskliniken Betriebsgesellschaft mbH🇦🇹Salzburg, AustriaRichard GreilSite contact+435725525801r.greil@salk.at