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Trial registered on ANZCTR


Registration number
ACTRN12622000080729
Ethics application status
Approved
Date submitted
23/11/2021
Date registered
21/01/2022
Date last updated
21/01/2022
Date data sharing statement initially provided
21/01/2022
Date results information initially provided
21/01/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
A study to evaluate multi-parametric MRI imaging in active surveillance cohort for low risk Prostate Cancer
Scientific title
Prospective, multi-centre, observational cohort study of multi-parametric MRI in active surveillance for low risk Prostate Cancer
Secondary ID [1] 305776 0
nil known
Universal Trial Number (UTN)
none
Trial acronym
The ‘MRIAS’ Study
Linked study record
none

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 324281 0
Condition category
Condition code
Cancer 321775 321775 0 0
Prostate

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Multi-parametric MRI scans will be performed as per standard of care for patients on active surveillance and assessed as per this protocol at Baseline, 1 year, 2 years and 3 years including follow-up up to 7 years consistent with the highest standards of prostate MRI:
• 3-Tesla magnet field strength
• 32-channel system with 14-channel spine coil and 18-channel pelvic phased array coil arrangement
• T1-weighted gradient spine echo sequence to identify biopsy haemorrhage artifact
• T2-weighted, high spatial resolution, anatomical imaging to identify and precisely localise areas of suspicion, and direct MRI-guided biopsy where performed;
• T2-weighted imaging in 3 planes with sagittal, coronal, axial and TSE images;
• Diffusion-Weighted Imaging with software derived Apparent Diffusion Co-efficient (ADC) quantitative analysis maps, and multiple B-values (0, 400, 800, 1400);
• Dynamic Contrast Enhanced imaging (DCE) with automatically-delivered IV gadolinium DTPA bolus 10ml at 3ml/ second followed by rapid sequences with temporal resolution of between 4-7 seconds between scans;
• Detailed quantitative analysis of DCEI imaging using K-trans colour maps and curve analysis according to PIRADS DCEI analytic guidelines;
• No use of Endo-rectal coils or MR Spectroscopy as per current guidelines
• Dedicated MRI physicists present for all scans to optimise protocols
• Approximate scan time 30minutes.
Intervention code [1] 322213 0
Diagnosis / Prognosis
Comparator / control treatment
The data will be retrospectively compared as per below:
Normal baseline MRI vs abnormal baseline MRI and then compared 1,2,3 and up to 7 years thereafter for disease progression.
MRI-directed cores at biopsy vs standard template biopsy which is conducted as per standard of care.
Control group
Active

Outcomes
Primary outcome [1] 329581 0
To evaluate Progression-free survival (biopsy criteria) at 3 years, in men on Active Surveillance with normal versus abnormal baseline MRI.
Timepoint [1] 329581 0
assessed from MRI scans conducted at Baseline, 1, 2, 3 years and biopsy.
Secondary outcome [1] 403100 0
Accuracy of baseline and surveillance MRI in identifying significant cancer, compared to surveillance biopsy & radical prostatectomy (subset analysis)
Timepoint [1] 403100 0
As per standard of care, patients undergo MRI scans and/or template biopsy 1, 2 and 3 years for surveillance post baseline. If the doctor deems that the patient requires radical prostatectomy due to prostate cancer progressing, they undergo surgery. MRI scans and biopsy will be compared with patients who are disease free to patients whose cancer progresses.
Secondary outcome [2] 404590 0
Accuracy of MRI-directed vs template cores for detecting significant cancer on Active surveillance (AS)
Timepoint [2] 404590 0
As per standard of care, patients undergo MRI scans and/or template biopsy 1, 2 and 3 years for surveillance post baseline. If the doctor deems that the patient requires radical prostatectomy due to prostate cancer progressing, they undergo surgery. MRI scans and biopsy will be compared with patients who are disease free to patients whose cancer progresses.
Secondary outcome [3] 404591 0
Treatment-free survival at 5-7 years (planned secondary analysis)
Timepoint [3] 404591 0
follow-up MRI and biopsy reports collected retrospectively which are conducted as per standard of care.
If patients underwent radical prostatectomy as part of disease progression.

Eligibility
Key inclusion criteria
Selection criteria: Men over 18years with a life expectancy of at least 10-15 years, choosing active surveillance and meeting low risk criteria.

Low risk criteria: men meeting all of the following criteria at baseline:
• PSA < 15
• DRE less than or equal to T2a
• Gleason less than or equal to 7 with no >5% grade 4 in any core
• Less than or equal to 33% of cores positive
• Less than or equal to 2 cores with any Gleason 4
• Less than or equal to 8mm cancer on all positive cores
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
• Women
• Age under 18yo
• Not meeting low risk criteria (PSA < 15, DRE less than or equal to T2a, Gleason less than or equal to 7 with no >5% grade 4 in any core, less than or equal to 33% of cores positive, less than or equal to 2 cores with any Gleason 4, less than or equal to8mm cancer on all positive cores)
• Inadequate baseline diagnostic biopsy using < 12 cores
• Inadequate baseline mpMRI not performed at a study location
• Not willing to undergo all MRIs & biopsies for entire 3-yr study period.
• Contra-indication to MRI (kidney disease eGFR < 40, past gadolinium reaction, non-conforming medical device, metallic foreign bodies, severe anxiety/ claustrophobia).
• Those at high risk of burden in research or the inability to provide informed consent, such as mentally ill, intellectually disabled or those highly dependent on medical care.

Study design
Purpose
Duration
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
SAMPLE SIZE CALCULATION
Detailed sample size calculations are performed with a consulting statistician using validated formulas and models from the published literature.

DETAILED ANALYSIS PLAN

Primary endpoint
Assessed via Kaplan-Meier survival analysis, including stratification according to baseline MRI group. Statistical testing for significance of difference between curves using the Log rank statistic and the generalised Wilcoxon rank-sum test if the PH assumption does not hold. The Cox proportional hazards model will be used and hazard ratios will be calculated and adjusted for baseline co-variates that are confounders and differ between groups.

Secondary endpoints
1) The accuracy of MRI in predicting (i) baseline biopsy (ii) surveillance biopsy & (iii) prostatectomy results will then be compared by constructing 2 x 2 tables and performing chi square analysis for sensitivity, specificity, PPV, NPV and accuracy. Then receiver operating characteristic (ROC) curves will be constructed and used to measure the Area Under the Curve (AUC) for MRI, using the 5-point PI-RADS scale. Multi-variate logistic regression analysis will be performed to assess for independent predictors of progression.
2) Accuracy of MRI-directed cores (manually directed, MR-US fusion-guided or MRI-guided) compared to standard template biopsy (trans-rectal or trans-perineal) for detection of significant cancer whilst on AS, in those with an abnormal MRI. MRI-directed cores will be labelled separately to standard template biopsy cores, such that in cases where MRI-directed cores and standard template cores were collected, they will be separately assessed via 2x2 tables and chi-square analysis, then accuracy estimates compared using the t-test for comparing two independent proportions.
3) Prostate cancer-specific, overall and metastasis-free survival at 10-15 years follow up will be assessed via KM survival analysis, stratified by baseline MRI group. Testing for difference between groups using the Log rank statistic/ generalised Wilcoxon rank-sum test will be performed. Cox proportional hazards model will be used and hazard ratios will be calculated and adjusted for baseline co-variates that are confounders and differ between groups.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
14/08/2014
Date of last participant enrolment
Anticipated
Actual
24/10/2017
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
300
Accrual to date
Final
172
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 21121 0
St Vincent's Private Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 35977 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 310133 0
Charities/Societies/Foundations
Name [1] 310133 0
Prostate Cancer Foundation of Australia
Country [1] 310133 0
Australia
Funding source category [2] 310171 0
Hospital
Name [2] 310171 0
St Vincent's Prostate Cancer Research Centre
Country [2] 310171 0
Australia
Primary sponsor type
Hospital
Name
St. Vincent's Private Hospital
Address
438 Victoria Street
Darlinghurst NSW 2010
Country
Australia
Secondary sponsor category [1] 311205 0
None
Name [1] 311205 0
Address [1] 311205 0
Country [1] 311205 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309821 0
St Vincent's Health Network; St Vincent's Hospital Human Research Ethics Committee.
Ethics committee address [1] 309821 0
St Vincent’s Health Network
Translational Research Centre
97-105 Boundary Street
Darlinghurst, NSW 2010
Ethics committee country [1] 309821 0
Australia
Date submitted for ethics approval [1] 309821 0
25/07/2013
Approval date [1] 309821 0
29/11/2013
Ethics approval number [1] 309821 0
13/160

Summary
Brief summary
The purpose of this study is to assess the accuracy and utility of MRI imaging in patients who are in active surveillance.
Who is it for?
You may be eligible for this study if you are an adult male, who has been diagnosed with low risk prostate cancer and your urologist has put you in active surveillance.
All participants will be asked to undertake an MRI scan, have their blood test for PSA test result and have the urologist conduct a direct rectal exam within (6 months prior to your biopsy, 1 yr, 2 yrs and 3yrs).

Follow-up will be as per standard of care with the urologist
Trial website
none
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 115506 0
Prof Phillip Stricker
Address 115506 0
St Vincent's Clinic
Level 10/438 Victoria St,
Darlinghurst NSW 2010
Country 115506 0
Australia
Phone 115506 0
+61 2 83826971
Fax 115506 0
Email 115506 0
phillip@stricker.com.au
Contact person for public queries
Name 115507 0
Mrs Shikha Agrawal
Address 115507 0
The Garvan Institute of Medical Research
The Kinghorn Cancer Centre Building
Level 6, 370 Victoria street
Darlinghurst NSW 2010
Country 115507 0
Australia
Phone 115507 0
+61 2 9355 5735
Fax 115507 0
Email 115507 0
s.agrawal@garvan.org.au
Contact person for scientific queries
Name 115508 0
Dr Paul Doan
Address 115508 0
The Garvan Institute of Medical Research
The Kinghorn Cancer Centre Building
Level 6, 370 Victoria street
Darlinghurst NSW 2010
Country 115508 0
Australia
Phone 115508 0
+61 2 9355 5735
Fax 115508 0
Email 115508 0
p.doan@garvan.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
Only aggregate data will be available in publications


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.