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Trial registered on ANZCTR


Registration number
ACTRN12620000463976
Ethics application status
Approved
Date submitted
9/03/2020
Date registered
9/04/2020
Date last updated
9/04/2020
Date data sharing statement initially provided
9/04/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Registry-based Study of Enzalutamide vs Abiraterone assessing cognitive function in ELderly patients with Metastatic Castration-Resistant Prostate Cancer
Scientific title
A prospective, open-label, multi-centre, registry-based randomised clinical trial comparing the cognitive impact of standard-of-care treatments in men aged 75 years or older that have metastatic castration-resistant prostate cancer.
Secondary ID [1] 300748 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
REAL-Pro
Linked study record
Nil

Health condition
Health condition(s) or problem(s) studied:
Metastatic Castration-Resistant Prostate Cancer 316590 0
Cognitive decline 316591 0
Depression 316592 0
Condition category
Condition code
Cancer 314818 314818 0 0
Prostate
Mental Health 314889 314889 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be stratified according to previous docetaxel treatment (Yes/No) and then randomised in a 1:1 ratio to one of two treatment arms described below.
Arm A
Abiraterone acetate 1000mg daily plus corticosteroid (dose, mode of administration and frequency/duration of corticosteroid treatment is determined by treating clinician)

Arm B
Enzalutamide 160mg daily

Both treatment arms are standard of care for this cohort of patients. Participants must commence treatment at full dose. Dose-adjustments or delays will be permitted at any other time point, as determined by the treating clinician.

a) The duration of the intervention is 11-13 weeks. Treatment may continue past this point as participants will continue with standard of care as determined by their treating clinician. No assessments will be made after 13 weeks post randomisation.
b) The mode of administration of Abiraterone acetate and Enzalutamide is via oral tablet.
c) Adherence to the intervention will not be monitored however, cessation of treatment prior to 13 weeks post randomisation will be recorded.

Intervention code [1] 317076 0
Treatment: Drugs
Comparator / control treatment
Abiraterone acetate 1000mg daily plus corticosteroid (dose, mode of administration and frequency/duration of corticosteroid treatment as determined by treating clinician) acts as a comparator/control Enzalutamide 160mg daily.

Enzalutamide 160mg daily acts as a comparator/control for Abiraterone acetate 1000mg daily plus corticosteroid (dose, mode of administration and frequency/duration of corticosteroid treatment as determined by treating clinician).

This study compares two standard of care treatments against each other. There is no placebo or other comparator.
Control group
Active

Outcomes
Primary outcome [1] 323175 0
Cognitive decline incidence
The proportion of patients with a higher Blessed Orientation-Memory-Cognition test score (by 1 or more points) at 12 (+/- 1) weeks of treatment as compared to baseline.
Timepoint [1] 323175 0
Participants will be assessed at baseline (within +/- 7 days of treatment commencing) and after 12 weeks (+/- 1 week) of treatment.
Primary outcome [2] 323211 0
Depression rate.
The proportion of patients with depression, as determined by the Geriatric Depression Scale tool as a score > 5 at 12 (+/- 1) weeks of treatment as compared to baseline.
Timepoint [2] 323211 0
Participants will be assessed at baseline (within +/- 7 days of treatment commencing) and after 12 weeks (+/- 1 week) of treatment.
Primary outcome [3] 323212 0
Falls rate.
The proportion of patients who experience at least one fall during the first 12 weeks following randomisation, as determined by the Falls Risk Questionnaire.
Timepoint [3] 323212 0
Participants will be assessed at baseline (within +/- 7 days of treatment commencing) and after 12 weeks (+/- 1 week) of treatment.
Secondary outcome [1] 381057 0
Overall survival (death from any cause).
Timepoint [1] 381057 0
The interval from date of randomisation to the date of death from any cause; or censoring at the date of most recent follow-up where the patient was known to be alive.
Secondary outcome [2] 381062 0
Prostate Specific Antigen response rate as assessed by blood test for PSA level.
Timepoint [2] 381062 0
The proportion of patients with 50% reduction in PSA at any time following randomisation up to 12 weeks post randomisation, compared to baseline level, with baseline defined as within (+/-) 7 days prior to commencing study treatment.

Eligibility
Key inclusion criteria
• Age greater than or equal to 75 years
• Diagnosis of metastatic castration-resistant prostate carcinoma
• Eligible for PBS-subsidised therapy with abiraterone or enzalutamide
• Suitable to receive full dose therapy
• Able to take oral medications
• Able to complete telephone interviews
Minimum age
75 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Previous systemic therapy for CRPC other than docetaxel.

Contraindication to abiraterone therapy include but are not limited to:
Uncontrolled hypertension.
Clinically significant ischemic heart disease or congestive cardiac failure
Significant hepatic dysfunction including chronic liver disease or active viral hepatitis; ALT or AST greater than or equal to 2.5 times upper limit of normal range or greater than or equal to 5 times upper limit of normal in presence of liver metastases.
Pituitary or adrenal dysfunction.
Contraindication to corticosteroids.

Contraindication to enzalutamide therapy include but are not limited to:
Previous seizures or a condition that confers a predisposition to seizures.
History of clinically significant neuropsychiatric event.
Clinically significant cognitive impairment.

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)
Central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
A Fisher's exact test with a 0.05 two-sided significance level will have 80% power to detect the difference between a proportion of 0.05 (abiraterone) and 0.19 (enzalutamide) when the sample size in each group is 90. Adjusted for 10% loss to follow-up, 100 patients will be randomised in each arm for a total sample size of 200.

Recruitment
Recruitment status
Recruiting
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,SA,VIC
Recruitment hospital [1] 16092 0
Ashford Cancer Centre: Adelaide Cancer Centre - Kurralta Park
Recruitment hospital [2] 16093 0
Bendigo Health Care Group - Bendigo Hospital - Bendigo
Recruitment hospital [3] 16094 0
Border Medical Oncology - Albury
Recruitment hospital [4] 16095 0
Goulburn Valley Health - Shepparton campus - Shepparton
Recruitment hospital [5] 16096 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 29605 0
5037 - Kurralta Park
Recruitment postcode(s) [2] 29606 0
3550 - Bendigo
Recruitment postcode(s) [3] 29607 0
2640 - Albury
Recruitment postcode(s) [4] 29608 0
3630 - Shepparton
Recruitment postcode(s) [5] 29609 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 305199 0
Hospital
Name [1] 305199 0
Victorian Comprehensive Cancer Centre
Address [1] 305199 0
Level 10, 305 Grattan Street Melbourne VIC 3000
Country [1] 305199 0
Australia
Funding source category [2] 305200 0
Other Collaborative groups
Name [2] 305200 0
ANZUP - Mundipharma clinical research fellowship
Address [2] 305200 0
Lifehouse, Level 6, 119-143 Missenden Road Camperdown NSW 2050
Country [2] 305200 0
Australia
Primary sponsor type
Other
Name
Walter and Eliza Hall Institute for Medical Research
Address
1G Royal Parade, Parkville Victoria 3052
Country
Australia
Secondary sponsor category [1] 305561 0
None
Name [1] 305561 0
Address [1] 305561 0
Country [1] 305561 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305552 0
Melbourne Health
Ethics committee address [1] 305552 0
300 Grattan Street (corner of Royal Parade) Parkville, Victoria 3050
Ethics committee country [1] 305552 0
Australia
Date submitted for ethics approval [1] 305552 0
30/01/2019
Approval date [1] 305552 0
01/04/2019
Ethics approval number [1] 305552 0

Summary
Brief summary
The purpose of this study is to see if there is a difference in cognitive decline between elderly patients treated with two common prostate cancer medications (enzalutamide and abiraterone acetate).

Who is it for?
You may be eligible for this study if you are a male aged 75 or over, and have a diagnosis of metastatic prostate cancer (cancer that has spread outside the prostate).

Study details
Participants in this study will be randomised by chance (like flipping a coin) into two groups. Both groups will receive one of two standard treatments. One group will receive Abiraterone acetate and a steroid as tablets and the other group will receive Enzalutamide as tablets. Both groups will have their treatment daily until their doctor decides they should stop.
As part of this study, participants will answer questionnaires about their ability to think, learn and memorise (cognition), their mood status and their risk of falling. They will also consent to researchers accessing their medical records for information about their cancer.

It is hoped this research will clarify if one of these medications has less of an impact on cognitive decline, mood or falls risk, which may help doctors in the decision of what medication to use for elderly patients in the future.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100766 0
Dr Ben Tran
Address 100766 0
Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne VIC 3000
Country 100766 0
Australia
Phone 100766 0
+61 3 9415 8850
Fax 100766 0
Email 100766 0
ben.tran@petermac.org
Contact person for public queries
Name 100767 0
Dr Arsha Anton
Address 100767 0
WEHI 1G Royal Parade Parkville Victoria 3052.
Country 100767 0
Australia
Phone 100767 0
+61 409146588
Fax 100767 0
Email 100767 0
arsha.anton@monash.edu
Contact person for scientific queries
Name 100768 0
Dr Arsha Anton
Address 100768 0
WEHI 1G Royal Parade Parkville Victoria 3052.
Country 100768 0
Australia
Phone 100768 0
+61 409146588
Fax 100768 0
Email 100768 0
arsha.anton@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD may be collected at a site level. However, IPD will not be made available to the Sponsor. The data that is collected by the Sponsor will not be re-identifiable at the Sponsor level. There are safeguards in place to minimise the risk of a privacy breach. They include analysing the data on an aggregated level and access to the data in a controlled environment with only authorised study personnel. Finally, enabling the availability of IPDs will not help meet the primary and secondary objectives of the study which are dependent on the results from the study population rather than on an individual basis.
What supporting documents are/will be available?
No other documents available
Summary results
No Results