COVID-19 studies are our top priority.

For new and updated trial submissions, we are processing trials as quickly as possible and appreciate your patience. We recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02446444




Registration number
NCT02446444
Ethics application status
Date submitted
4/05/2015
Date registered
18/05/2015
Date last updated
2/04/2021

Titles & IDs
Public title
Enzalutamide in Androgen Deprivation Therapy With Radiation Therapy for High Risk, Clinically Localised, Prostate Cancer
Scientific title
Randomised Phase 3 Trial of Enzalutamide in Androgen Deprivation Therapy With Radiation Therapy for High Risk, Clinically Localised, Prostate Cancer: ENZARAD
Secondary ID [1] 0 0
ACTRN12614000126617
Secondary ID [2] 0 0
ANZUP1303
Universal Trial Number (UTN)
Trial acronym
ENZARAD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostatic Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Enzalutamide
Treatment: Drugs - Conventional NSAA
Treatment: Drugs - LHRHA
Treatment: Other - External Beam Radiotherapy (78 Gy in 39 fractions or 46 Gy in 23 fractions plus brachytherapy boost)

Experimental: Enzalutamide - 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)

Active Comparator: Conventional Non-steroidal Anti-androgen (NSAA) - 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)


Treatment: Drugs: Enzalutamide


Treatment: Drugs: Conventional NSAA


Treatment: Drugs: LHRHA


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


Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
5 years
Secondary outcome [1] 0 0
Overall survival - Overall survival (OS) is defined as the interval from the date of randomisation to date of death from any cause, or the date of last known follow-up alive.
Timepoint [1] 0 0
5 years
Secondary outcome [2] 0 0
Prostate cancer-specific survival - Prostate cancer-specific survival is defined as the interval from the date of randomisation to the date of death from prostate cancer, or the date of last known follow-up alive.
Timepoint [2] 0 0
5 years
Secondary outcome [3] 0 0
PSA (Prostate-Specific Antigen) progression-free survival - PSA progression-free survival is defined as the interval from the date of randomisation to the date of first evidence of PSA progression, clinical progression, or death from any cause, whichever occurs first, or the date of last known follow-up without PSA progression and without clinical progression.
PSA progression as defined by the Phoenix criteria: an increase in PSA of more than 2ng/mL above the nadir (lowest) PSA level.
Timepoint [3] 0 0
5 years
Secondary outcome [4] 0 0
Clinical progression-free survival - Clinical progression-free survival is defined as the interval from the date of randomisation to the date of first clinical evidence of disease progression or death from any cause, whichever occurs first, or the date of last known follow-up alive without clinical progression.
Clinical evidence of disease progression includes evidence of progression or recurrence on imaging, clinical examination, development of symptoms attributable to cancer progression, or initiation of other anticancer treatment for prostate cancer.
Timepoint [4] 0 0
5 years
Secondary outcome [5] 0 0
Time to subsequent hormonal therapy - Time to subsequent hormone therapy is the interval from randomisation to the first date that androgen deprivation therapy is recommenced for the treatment of recurrent (or progressive) prostate cancer, or the date of last known follow-up without recommencement of androgen deprivation therapy.
Timepoint [5] 0 0
5 years
Secondary outcome [6] 0 0
Time to castration-resistant disease (PCWG2 criteria) - Castration resistant prostate cancer (CRPC) is defined, per PCWG2, by a rising PSA that is greater than 2ng/mL higher than the most recent nadir with a testosterone < 50 ng/dL (<1.7 nmol/L); the rise has to be at least 25% over the most recent nadir; and, the rise has to be confirmed by a second PSA at least three weeks later. The time to castration-resistant prostate cancer is defined as the interval from randomisation to the date that the PSA first met the criteria defined above (i.e. the date of the first PSA to meet these criteria, not the date of the subsequent confirmatory test), or the date of last known follow-up without CRPC.
Timepoint [6] 0 0
5 years
Secondary outcome [7] 0 0
Safety (adverse events - CTCAE v4.03) - The NCI Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03) will be used to classify and grade the intensity of adverse events occurring until 30 days after the last dose of study treatment.
Timepoint [7] 0 0
5 years
Secondary outcome [8] 0 0
Health related quality of life (HRQL) - HRQL will be reported by participants using the EORTC core quality of life questionnaire (QLQ C-30) and prostate cancer specific module (PR-25). The EQ-5D-5L will be used to derive utility scores suitable for quality adjusted survival analyses
Timepoint [8] 0 0
5 years
Secondary outcome [9] 0 0
Health outcomes relative to costs (incremental cost effectiveness ratio) - Information on the following areas of health-care resource usage will be collected: hospitalisations, visits to health professionals, and medications. Quality-adjusted survival (QAS) time will be used to quantify the incremental effectiveness of adding enzalutamide to standard treatment.
Timepoint [9] 0 0
5 years

Eligibility
Key inclusion criteria
Men with localised prostate cancer at high risk for recurrence deemed suitable for external
beam radiation therapy.



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
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key 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 (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.

5. 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

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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Blacktown Hospital - Blacktown
Recruitment hospital [2] 0 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [3] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [4] 0 0
Genesis Cancer Care Newcastle - Gateshead
Recruitment hospital [5] 0 0
Gosford Hospital - Gosford
Recruitment hospital [6] 0 0
St George Hospital - Kogarah
Recruitment hospital [7] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [8] 0 0
Orange Health Service - Orange
Recruitment hospital [9] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [10] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [11] 0 0
St Vincent's Hospital - Sydney
Recruitment hospital [12] 0 0
Tamworth Rural Referral Hospital - Tamworth
Recruitment hospital [13] 0 0
Sydney Adventist Hospital - Wahroonga
Recruitment hospital [14] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [15] 0 0
Westmead Hospital - Westmead
Recruitment hospital [16] 0 0
Wollongong Hospital - Wollongong
Recruitment hospital [17] 0 0
Genesis Cancer Care Queensland - Wesley and Chermside - Auchenflower
Recruitment hospital [18] 0 0
Townsville Hospital - Douglas
Recruitment hospital [19] 0 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [20] 0 0
Nambour General Hospital - Nambour
Recruitment hospital [21] 0 0
Radiation Oncology Services Mater Centre - South Brisbane
Recruitment hospital [22] 0 0
ICON - Gold Coast (formerly ROC Gold Coast) - Southport
Recruitment hospital [23] 0 0
ICON - Toowoomba (formerly ROC Toowoomba) - Toowoomba
Recruitment hospital [24] 0 0
Genesis Cancer Care Queensland - Tugun and Southport - Tugun
Recruitment hospital [25] 0 0
Princess Alexandra Hospital Brisbane - Woolloongabba
Recruitment hospital [26] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [27] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [28] 0 0
Ashford Cancer Centre Research (Adelaide Cancer Centre) - Kurralta Park
Recruitment hospital [29] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [30] 0 0
Peter MacCallum Cancer Centre - Bendigo
Recruitment hospital [31] 0 0
Peter MacCallum Cancer Centre (Moorabbin Campus) - Bentleigh East
Recruitment hospital [32] 0 0
Eastern Health (Box Hill Hospital) - Box Hill
Recruitment hospital [33] 0 0
Genesis Care - Epping (formerly EROC) - Epping
Recruitment hospital [34] 0 0
Genesis Care - Western (formerly WROC) - Footscray
Recruitment hospital [35] 0 0
Genesis Care - Frankston (formerly FROC) - Frankston
Recruitment hospital [36] 0 0
Austin Health - Heidelberg
Recruitment hospital [37] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [38] 0 0
Epworth HealthCare - Richmond - Richmond
Recruitment hospital [39] 0 0
Genesis Care - Ringwood (formerly RROC) - Ringwood East
Recruitment hospital [40] 0 0
Sunshine Hospital - St Albans
Recruitment hospital [41] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2560 - Campbelltown
Recruitment postcode(s) [3] 0 0
2050 - Camperdown
Recruitment postcode(s) [4] 0 0
2290 - Gateshead
Recruitment postcode(s) [5] 0 0
2250 - Gosford
Recruitment postcode(s) [6] 0 0
2217 - Kogarah
Recruitment postcode(s) [7] 0 0
2170 - Liverpool
Recruitment postcode(s) [8] 0 0
2800 - Orange
Recruitment postcode(s) [9] 0 0
2131 - Randwick
Recruitment postcode(s) [10] 0 0
2065 - St Leonards
Recruitment postcode(s) [11] 0 0
2010 - Sydney
Recruitment postcode(s) [12] 0 0
2340 - Tamworth
Recruitment postcode(s) [13] 0 0
2076 - Wahroonga
Recruitment postcode(s) [14] 0 0
2298 - Waratah
Recruitment postcode(s) [15] 0 0
2145 - Westmead
Recruitment postcode(s) [16] 0 0
2500 - Wollongong
Recruitment postcode(s) [17] 0 0
4066 - Auchenflower
Recruitment postcode(s) [18] 0 0
4814 - Douglas
Recruitment postcode(s) [19] 0 0
4006 - Herston
Recruitment postcode(s) [20] 0 0
4560 - Nambour
Recruitment postcode(s) [21] 0 0
4101 - South Brisbane
Recruitment postcode(s) [22] 0 0
4215 - Southport
Recruitment postcode(s) [23] 0 0
4350 - Toowoomba
Recruitment postcode(s) [24] 0 0
4224 - Tugun
Recruitment postcode(s) [25] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [26] 0 0
5000 - Adelaide
Recruitment postcode(s) [27] 0 0
5042 - Bedford Park
Recruitment postcode(s) [28] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [29] 0 0
7000 - Hobart
Recruitment postcode(s) [30] 0 0
3550 - Bendigo
Recruitment postcode(s) [31] 0 0
3165 - Bentleigh East
Recruitment postcode(s) [32] 0 0
3128 - Box Hill
Recruitment postcode(s) [33] 0 0
3076 - Epping
Recruitment postcode(s) [34] 0 0
3011 - Footscray
Recruitment postcode(s) [35] 0 0
3199 - Frankston
Recruitment postcode(s) [36] 0 0
3084 - Heidelberg
Recruitment postcode(s) [37] 0 0
3002 - Melbourne
Recruitment postcode(s) [38] 0 0
3121 - Richmond
Recruitment postcode(s) [39] 0 0
3135 - Ringwood East
Recruitment postcode(s) [40] 0 0
3021 - St Albans
Recruitment postcode(s) [41] 0 0
6149 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
Austria
State/province [2] 0 0
Salzburg
Country [3] 0 0
Belgium
State/province [3] 0 0
Kortrijk
Country [4] 0 0
Ireland
State/province [4] 0 0
Co Cork
Country [5] 0 0
Ireland
State/province [5] 0 0
Co Galway
Country [6] 0 0
Ireland
State/province [6] 0 0
Dublin 7
Country [7] 0 0
Ireland
State/province [7] 0 0
Dublin
Country [8] 0 0
New Zealand
State/province [8] 0 0
Auckland
Country [9] 0 0
New Zealand
State/province [9] 0 0
Christchurch
Country [10] 0 0
New Zealand
State/province [10] 0 0
Palmerston North
Country [11] 0 0
Slovenia
State/province [11] 0 0
Ljubljana
Country [12] 0 0
Spain
State/province [12] 0 0
Barcelona
Country [13] 0 0
Spain
State/province [13] 0 0
Gipuzkoa
Country [14] 0 0
Spain
State/province [14] 0 0
Salamanca
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Cardiff
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Hampshire
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Kent
Country [18] 0 0
United Kingdom
State/province [18] 0 0
London
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Scotland
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Bath
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Cambridge
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Other
Name
University of Sydney
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
National Health and Medical Research Council, Australia
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Cancer Trials Ireland
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
TROG- Trans Tasman Radiation Oncology Group
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
European Organisation for Research and Treatment of Cancer - EORTC
Address [5] 0 0
Country [5] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02446444
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Scott Williams
Address 0 0
ANZUP and Peter MacCallum Cancer Centre
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications