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Trial registered on ANZCTR


Registration number
ACTRN12616001707459
Ethics application status
Approved
Date submitted
7/12/2016
Date registered
13/12/2016
Date last updated
5/03/2019
Date data sharing statement initially provided
5/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Prostate Cancer Vitamin D Clinical Trial
Scientific title
A phase II randomised controlled trial of vitamin D in localised prostate cancer cases with intermediate risk of progression (ProsD).
Secondary ID [1] 290599 0
NA
Universal Trial Number (UTN)
NA
Trial acronym
ProsD
Linked study record
NA

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer progression 301072 0
Vitamin D in preventing prostate cancer progression 301075 0
Condition category
Condition code
Cancer 300851 300851 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Men in the intervention arm will take one vitamin D tablet orally (50,000IU), every month, for 24 months. To monitor adherence, each participant will be sent a reminder SMS and email reminding them to take their monthly tablet, when it is due. Each man will be followed up one week later by telephone to ensure compliance and check his well-being.
Intervention code [1] 296460 0
Treatment: Other
Comparator / control treatment
Men in the control arm will take one placebo tablet orally, every month, for 24 months. To monitor adherence, each participant will be sent a reminder SMS and email reminding them to take their monthly tablet. Each man will be followed up one week later by telephone to ensure compliance and check well-being.

The placebo tablet contains the following ingredients (mg/tablet):
Calcium hydrogen phosphate dehydrate (43.70 mg)
Colloidal anhydrous silica
Croscarmellose sodium (4.94 mg)
Macrogol
Magnesium stearate (0.49 mg)
Mica-based pearlescent pigment
Microcrystalline cellulose (148.12 mg)
Polysorbate 80
Polyvinyl alcohol – part hydrolysed
Talc
Titanium dioxide
Control group
Placebo

Outcomes
Primary outcome [1] 300268 0
Active therapy-free survival (ATFS) will be defined as men who do not undergo any active therapy (e.g. radical prostatectomy or radiotherapy) during the course of the trial. This will be determined by their treating urologist.
Timepoint [1] 300268 0
24 months
Secondary outcome [1] 329559 0
Conversion to active therapy due to non-clinical reasons, this is the number of patients opting out of AS for non-cancer progression (e.g. anxiety).
Timepoint [1] 329559 0
24 months

Eligibility
Key inclusion criteria
-Diagnosed within the last 6 months
-Men who were previously diagnosed with low-risk disease and whose disease have recently been upgraded (in the past 6 months) to fit our eligibility criteria, will also be eligible to participate in our study.
-Had an mpMRI (centrally reviewed, not limited to any PIRADS score) and:
-Gleason score = 7 (e.g. Gleason grade 3+4) or
- 3 or more positive biopsy core (which may include Gleason 6) or
-Clinical stage T2 (which may include Gleason 6) or
-PSA>10 ng/mL (which may include Gleason 6)

Minimum age
50 Years
Maximum age
80 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Men with low risk disease:
*No visible tumour on MRI or
*Gleason score 6 or less and
*PSA<10ng/mL and
*Clinical stage <T2

Men with high risk disease:
*Gleason score 8 or more or
*PSA>20ng/mL or
*Clinical stage T3 or T4 or N/M >0.

Other exclusion criteria are:
* Daily Vitamin D supplementation more than 50% of RDI (more than 300IU/day).
* Hyperparathyroidism, hypercalcaemia, or osteomalacia.
* With a glomerular filtration rate (GFR) below 30 which will include those with severe loss of kidney function, and that is, to exclude anyone with Stage 4 or Stage 5 kidney disease 4. *History of renal calculi.
* Taking orlistat, cholesterol-lowering drug called bile acid sequestrants such as cholestyramine and cholestipol or other drugs known to reduce vitamin D absorption.
*Those with gastrointestinal abnormalities that may affect nutrient absorption such as, those who are unable to swallow oral medication, those who have clinically diagnosed malabsorption syndrome with evidence of malabsorption, or those who have had prior surgical procedure affecting absorption.
* We will also exclude those unable to comprehend study information and its requirements for intellectual reasons, or if they do not have sufficient English proficiency.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by Interactive Voice Response System IVRS).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The method of randomisation is that of minimisation, through a central Interactive Voice Response System IVRS). Treatment allocation will be balanced using this method based on the strata (identified in the protocol). This will ensure that there is a reasonable balance in treatment allocation over the course of the trial.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The primary outcome for the trial is the change from AS to active therapy by 24 months. This is currently estimated to be ~35% at 2 years for intermediate-risk patients on AS. Using Simon’s two-stage design, a sample size of 80 patients in the group receiving the vitamin D supplement would have > 80% power with 95% confidence to exclude a success rate of 65% in favour of a more interesting rate of 77.5% (i.e. active therapy rate of 22.5% rather than 35%). If 8 of the first 24 (33.3%) patients in the intervention group have progressed after 2 years of therapy, consideration will be given to modifying the intervention or stopping the study for futility. In order to obtain contemporary estimates for the control group it is proposed to randomise patients 2:1 resulting in a total sample size of 120 patients (80 vitamin D supplementation, 40 placebo controls).

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,QLD,VIC
Recruitment hospital [1] 6967 0
Macquarie University Hospital - Macquarie Park
Recruitment hospital [2] 6968 0
Westmead Private Hospital - Westmead
Recruitment hospital [3] 6970 0
St George Private Hospital - Kogarah
Recruitment hospital [4] 6971 0
Hurstville Private - Hurstville
Recruitment hospital [5] 6972 0
The Wesley Hospital - Auchenflower
Recruitment hospital [6] 6973 0
Australian Urology Associates - Malvern
Recruitment hospital [7] 8500 0
Bairnsdale Regional Health Service - Bairnsdale
Recruitment postcode(s) [1] 14663 0
2109 - Macquarie Park
Recruitment postcode(s) [2] 14664 0
2145 - Westmead
Recruitment postcode(s) [3] 14666 0
2217 - Kogarah
Recruitment postcode(s) [4] 14667 0
2220 - Hurstville
Recruitment postcode(s) [5] 14668 0
4066 - Auchenflower
Recruitment postcode(s) [6] 14669 0
3144 - Malvern
Recruitment postcode(s) [7] 14673 0
2065 - St Leonards
Recruitment postcode(s) [8] 14674 0
2103 - Mona Vale
Recruitment postcode(s) [9] 14675 0
2099 - Dee Why
Recruitment postcode(s) [10] 14812 0
2076 - Wahroonga
Recruitment postcode(s) [11] 16592 0
2148 - Blacktown
Recruitment postcode(s) [12] 16593 0
2010 - Darlinghurst
Recruitment postcode(s) [13] 17618 0
2525 - Figtree
Recruitment postcode(s) [14] 17619 0
2560 - Campbelltown
Recruitment postcode(s) [15] 17620 0
4000 - Brisbane
Recruitment postcode(s) [16] 18628 0
2500 - Wollongong
Recruitment postcode(s) [17] 18629 0
2560 - Campbelltown North
Recruitment postcode(s) [18] 18630 0
2751 - Penrith
Recruitment postcode(s) [19] 24318 0
3150 - Glen Waverley

Funding & Sponsors
Funding source category [1] 295026 0
Charities/Societies/Foundations
Name [1] 295026 0
The Prostate Cancer Foundation of Australia: Movember Clinical Trial Award
Address [1] 295026 0
Prostate Cancer Foundation of Australia
Level 5
437 St Kilda Road
Melbourne, VIC 3004
Country [1] 295026 0
Australia
Primary sponsor type
University
Name
Macquarie University
Address
Faculty of Medicine and Health Sciences
Macquarie University
Level 4, Suite 407
2 Technology Place
Macquarie University, NSW 2109
Country
Australia
Secondary sponsor category [1] 293843 0
Charities/Societies/Foundations
Name [1] 293843 0
Cancer Council NSW
Address [1] 293843 0
Cancer Research Division
Cancer Council NSW
PO Box 572
Kings Cross, NSW 1340
Country [1] 293843 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296381 0
Belllberry Limited
Ethics committee address [1] 296381 0
Belllberry Limited
129 Glen Osmond Road
Eastwood, SA 5063
Ethics committee country [1] 296381 0
Australia
Date submitted for ethics approval [1] 296381 0
09/09/2016
Approval date [1] 296381 0
16/01/2017
Ethics approval number [1] 296381 0
2016-06-459-A-1
Ethics committee name [2] 296382 0
Macquarie University Ethics Committee
Ethics committee address [2] 296382 0
Ethics Secretariat Research Office
Level 3, C5C Building
Macquarie University, NSW 2109
Ethics committee country [2] 296382 0
Australia
Date submitted for ethics approval [2] 296382 0
06/02/2017
Approval date [2] 296382 0
21/03/2017
Ethics approval number [2] 296382 0
5201700188

Summary
Brief summary
The primary purpose of this trial is to evaluate the efficacy of vitamin D supplementation for the prevention of progression in men with prostate cancer who have an immediate risk of progression.

Who is it for?
Men are eligible to participate in this trial if they are aged 50 to <80 and have been diagnosed with localised prostate cancer with intermediate risk of progression, for which they have chosen to go on active surveillance.

Study details
All participants enrolled in this trial will be randomly allocated (by chance) to receive either vitamin D tablets, or to receive inactive sham tablets. Tablets in both groups will be taken orally, once per month, for two years. Participants will be followed up at the end of this period to assess for incidence of disease progression and commencement of active therapy.

It is hoped that the findings from this trial will provide information on whether vitamin D supplementation is effective for preventing disease progression in men with prostate cancer.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 70674 0
Prof Howard Gurney
Address 70674 0
Faculty of Medicine and Health Sciences
Macquarie University
Level 4, Suite 407
2 Technology Place
Macquarie University, NSW 2109
Country 70674 0
Australia
Phone 70674 0
+ 61 2 9812 3561
Fax 70674 0
Email 70674 0
Howard.gurney@mq.edu.au
Contact person for public queries
Name 70675 0
Dr Visalini Nair-Shalliker
Address 70675 0
Cancer Research Division
Cancer Council NSW
PO Box 572
Kings Cross, NSW 1340
Country 70675 0
Australia
Phone 70675 0
+61 293341410
Fax 70675 0
+ 61 2 8302 3518
Email 70675 0
enquiriesProsD@nswcc.org.au
Contact person for scientific queries
Name 70676 0
Dr Visalini Nair-Shalliker
Address 70676 0
Cancer Research Division
Cancer Council NSW
PO Box 572
Kings Cross, NSW 1340

Country 70676 0
Australia
Phone 70676 0
+ 61 2 9334 1410
Fax 70676 0
+ 61 2 8302 3518
Email 70676 0
enquiriesProsD@nswcc.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Ethical committee approval will be required for access to original data from this trial. Ethics submissions to support requests for data access should be directed to the Bellberry Human Research Ethics Committee at the following address: http://www.bellberry.com.au; parallel contact should be made with the trial investigators.
What supporting documents are/will be available?
Study protocol
Statistical analysis plan
Informed consent form
Ethical approval
Summary results
No Results