Localised prostate cancer at high risk of recurrence MedDRA version: 20.0 Level: PT Classification code 10060862 Term: Prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Xtandi (Enzalutamide)
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: ENZALUTAMIDE
CAS Number: 915087-33-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentrati
Sponsors
Cancer Trials Ireland
Eligibility
Sex/Gender
Male
Inclusion criteria
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 ISUP Consensus 2005 (13) 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 2. Age =18 yrs 3. Adequate bone marrow function Hb =100g/L and WCC = 4.0 x 109/L and platelets =100 x 109/L 4. Adequate liver function: ALT 30 ml/min (Cockroft-Gault) 6. 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 HRQL questionnaires UNLESS is unable to complete because of literacy or limited vision 10. Signed, written, informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 400 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 400
Exclusion criteria
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 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. 5. 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 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 a. 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: a. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine effects on: 1) Metastasis-free survival (metastasis or death from any cause, MFS);Secondary Objective: To determine effects on: 2) Overall survival (death from any cause, OS) 3) Prostate cancer-specific survival (death from prostate cancer) 4) PSA progression-free survival (Phoenix criteria or death from any cause, PSA-PFS) 5) Clinical progression-free survival (imaging, symptoms, signs, initiation of other anti-cancer treatment, or death from any cause, clinical-PFS) 6) Time to subsequent hormonal therapy (restarting ADT) 7) Time to castration-resistant disease (PCWG2 criteria) 8) Safety (adverse events - CTCAE v4.03) 9) Health related quality of life (EORTC QLQC-30, PR-25 & EQ-5D-5L) 10) Health outcomes relative to costs (incremental cost effectiveness ratio);Primary end point(s): To determine effects on: 1) Metastasis-free survival (metastasis or death from any cause, MFS);Timepoint(s) of evaluation of this end point: Assuming the study is not terminated early, the final analysis is planned to be undertaken after the required number of MFS events have occurred. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To determine effects on: 2) Overall survival (death from any cause, OS) 3) Prostate cancer-specific survival (death from prostate cancer) 4) PSA progression-free survival (Phoenix criteria or death from any cause, PSA-PFS) 5) Clinical progression-free survival (imaging, symptoms, signs, initiation of other anti-cancer treatment, or death from any cause, clinical-PFS) 6) Time to subsequent hormonal therapy (restarting ADT) 7) Time to castration-resistant disease (PCWG2 criteria) 8) Safety (adverse events - CTCAE v4.03) 9) Health related quality of life (EORTC QLQC-30, PR-25 & EQ-5D-5L) 10) Health outcomes relative to costs (incremental cost effectiveness ratio);Timepoint(s) of evaluation of this end point: Assuming the study is not terminated early, the final analysis is planned to be undertaken after the required number of MFS events have occurred. | — |
Countries
Australia, Austria, Belgium, Ireland, Italy, New Zealand, Slovenia, Spain, United Kingdom, United States
Contacts
Public ContactHead of Clinical Operations
Cancer Trials Ireland
Outcome results
None listed