Randomised phase 3 trial of enzalutamide in androgen deprivation therapy with radiation therapy for high risk, clinically localised, prostate cancer

Phase 3

Active, not recruiting

• Conditions: Prostate Cancer; Cancer - Prostate

• Registration Number: ACTRN12614000126617
• Lead Sponsor: HMRC Clinical Trials Centre (CTC) , University of Sydney

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-02-03
• Last Update Posted: 6 November 2023

Recruitment & Eligibility

• Status: Active, not recruiting
• Sex: Male
• Target Recruitment: 802

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: a) Gleason score 8-10 OR b) Gleason score of 4+3 AND clinical T2b-4 AND PSA >20nj/mL OR c) 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
4) Adequate liver function
5) Adequate renal function
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 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 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), 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 CT / MRI and 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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Metastasis-free survival (metastasis or death from any cause, MFS)[ Follow-up until approximately 200 MFS events are observed.]