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Trial registered on ANZCTR


Registration number
ACTRN12622000188730
Ethics application status
Approved
Date submitted
10/11/2021
Date registered
3/02/2022
Date last updated
17/09/2023
Date data sharing statement initially provided
3/02/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Prospective cross-sectional study of 68Ga-PSMA PET/CT in addition to mpMRI in men undergoing 12-month confirmatory biopsy during Active Surveillance for low- or intermediate-risk prostate cancer
Scientific title
Diagnostic accuracy of 68Ga-PSMA PET/CT in addition to mpMRI in men undergoing 12-month confirmatory biopsy during Active Surveillance for low- or intermediate-risk prostate cancer
Secondary ID [1] 305747 0
nil Known
Universal Trial Number (UTN)
none
Trial acronym
PIAS study
Linked study record
none

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 324243 0
Condition category
Condition code
Cancer 321730 321730 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All patients newly enrolled onto Active Surveillance program will undergo a limited (pelvic only) 68Ga-PSMA PET/CT in addition to their standard-of-care surveillance mpMRI within 3 months prior to their 12-month (range 6-18-months) confirmatory biopsy.
68Ga-PSMA (HBED CC-11), will be produced on-site compliant to the Good Laboratory Practices procedure. Radio-pharmacy quality control will be undertaken using a high-pressure liquid chromatography (HPLC). 68Ga-PSMA (HBED CC-11) 1.8-2.2MBq/kg, subject to variation in yield from Ge-68/Ga-68 generator will be administered. A limited field of view PSMA PET of the pelvis (minimum of 3 minutes/bed stop) will be undertaken around 60 minutes (+/- 10 minutes) post injection with a non-contrast-enhanced CT scan (pelvis) performed around 60 minutes (+/- 10 minutes) post tracer injection.
Intervention code [1] 322149 0
Diagnosis / Prognosis
Comparator / control treatment
Participants in the study will be required to undergo a mpMRI within 3 months of a confirmatory biopsy as per standard of care.
Control group
Active

Outcomes
Primary outcome [1] 329494 0
Sensitivity and specificity of combined mpMRI (gold standard) and PSMA PET to detect or exclude significant malignancy requiring definitive therapy (treatment endpoint) on confirmatory biopsy in men on AS
Timepoint [1] 329494 0
once mpMRI/PSMA PET scan have been completed upon data analysis
Secondary outcome [1] 402782 0
Sensitivity and specificity of mpMRI and PSMA PET alone to detect progression on biopsy (pathologic endpoint) for men on AS using pre-defined histological inclusion and progression criteria
Timepoint [1] 402782 0
PSMA PET, mpMRI and biopsy reports will be collected prior to date of AS diagnosis and after study enrolment.
Secondary outcome [2] 405497 0
Comparison of index lesion identification by template biopsies vs MRI targeted lesions vs PSMA targeted lesions
Timepoint [2] 405497 0
PSMA PET, mpMRI and biopsy reports will be collected prior to date of AS diagnosis and after study enrolment.
Secondary outcome [3] 405498 0
Comparison of the accuracy of targeted vs template biopsy to see if template biopsy can be avoided
Timepoint [3] 405498 0
biopsy reports will be collected prior to date of AS diagnosis and after study enrolment for comparison.
Secondary outcome [4] 405499 0
Evaluation of concordance of lesions identified on final histopathology and each imaging modality (PSMA PET and/or mpMRI) in the subset of patients proceeding to RP
Timepoint [4] 405499 0
PSMA PET, mpMRI and biopsy reports will be collected prior to date of AS diagnosis and after study enrolment.
RP reports will be collected from referring doctor for patients who progress to RP
Secondary outcome [5] 405500 0
Sensitivity and specificity of blood and urine samples to detect progression on biopsy (pathologic endpoint) for men on AS using pre-defined histological inclusion and progression criteria compared with PSMA/MRI
Timepoint [5] 405500 0
PSMA PET, mpMRI and biopsy reports will be collected prior to date of AS diagnosis and after study enrolment.
urine and blood collected at the enrolment visit and stored for future analysis
Secondary outcome [6] 405502 0
Cost-effectiveness analysis (assessed based on hospital resources and costs used to conduct annual biopsy) and out of pocket expenses to patients.
Timepoint [6] 405502 0
During the statistical analysis process

Eligibility
Key inclusion criteria
1 18 years or greater of age
2 Life expectancy of 10 years or greater
3 Newly diagnosed PCa deemed suitable for AS by treating urologist and not yet had a 12-month confirmatory biopsy on AS
4 A diagnosis of PCa meeting the following histopathological criteria:
o Organ-confined PCa: cT1-2a, cN0 and/or cM0/x
o ISUP Grade Group 2 PCa with < 20% Gleason pattern 4 overall and in each location; or
o ISUP Grade Group 1 PCa with ANY of the following high-risk features:
> 30% maximum cancer core involvement of any single core; or
> 6 mm cancer in any core; or
> 4 locations with cancer on biopsy; or
PI-RADS V2.1 4 or 5 lesion on baseline mpMRI
Focus on PSMA PET suspicious for PCa (SUVmax > 4 in PZ or > 5 in TZ)
5 No evidence of intraductal or cribriform architecture or EPE
6 No previous PCa treatment
7 Able to provide written informed consent to and willing to remain on AS
8 Planned for confirmatory biopsy within next 12 months following enrolment onto the study
9 Able to give written informed consent to, willing to participate and comply with the study
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
• Inability/incapacity to provide written informed consent to either AS or study
• Unwilling to remain on AS for the duration of study
• Has a diagnosis of PCa deemed not suitable for AS and treating urologist/not meeting ideal histological criteria
• Has had prior treatment for PCa
• Has had a prior normal or non-suspicious PSMA PET within 2 years of confirmatory biopsy
• Has a contraindication to mpMRI or PSMA PET

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised 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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
Sample size calculation
Sample size calculations were performed with a consulting statistician using validated formulas and models from the published literature.
Based on pilot data, it is estimated that a sample size of 225 will be required to detect a NPV ratio of 1.3 comparing PSMA PET in addition to mpMRI verse mpMRI alone, under a paired study design, with 80% power and at a two-sided significance level of 0.0525.
Statistical analysis
The summary statistics of diagnostic accuracy measures including sensitivity, specificity, PPV, NPV, overall diagnostic accuracy, the area under the receiver operating characteristic (ROC) curve (AUC) will be calculated with 95% CI for both PSMA PET with mpMRI and mpMRI alone.
The McNemar’s test of two correlated proportions will used to compare the paired data of PSMA PET with mpMRI, and mpMRI alone in sensitivity and specificity. A permutation test procedure will be used to compare paired data AUCs. The comparison in PPV and NPV between the two diagnostic approaches will be based on the relative ratio and involves multinomial-Poisson transformation. The generalised linear regression model approach will also be used to compare PPVs and NPVs, with control for patients’ characteristics.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
11/11/2021
Date of last participant enrolment
Anticipated
30/11/2024
Actual
Date of last data collection
Anticipated
30/11/2025
Actual
Sample size
Target
225
Accrual to date
50
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 21070 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 35920 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 310107 0
Hospital
Name [1] 310107 0
St. Vincent's Prostate Cancer Research Centre
Country [1] 310107 0
Australia
Funding source category [2] 314829 0
Other
Name [2] 314829 0
Ramaciotti Health Investment Grant
Country [2] 314829 0
Australia
Funding source category [3] 314830 0
Hospital
Name [3] 314830 0
St Vincent's Private Hospital
Country [3] 314830 0
Australia
Funding source category [4] 314831 0
Hospital
Name [4] 314831 0
St Vincent's Curran Foundation
Country [4] 314831 0
Australia
Primary sponsor type
Hospital
Name
St. Vincent's Prostate Cancer Research Centre
Address
Level 10/438 Victoria St,
Darlinghurst NSW 2010
Country
Australia
Secondary sponsor category [1] 311171 0
None
Name [1] 311171 0
Address [1] 311171 0
Country [1] 311171 0
Other collaborator category [1] 282066 0
Hospital
Name [1] 282066 0
The Wesley Hospital
Address [1] 282066 0
40 Chasely St,
Auchenflower QLD 4066
Country [1] 282066 0
Australia
Other collaborator category [2] 282067 0
Hospital
Name [2] 282067 0
St. Vincent's Hospital
Address [2] 282067 0
370 Victoria Street
Darlinghurst NSW 2010
Country [2] 282067 0
Australia
Other collaborator category [3] 282812 0
Hospital
Name [3] 282812 0
Cabrini Malvern
Address [3] 282812 0
183 Wattletree Rd
Malvern VIC 3144
Country [3] 282812 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309795 0
St Vincent's Hospital Human Research Ethics Committee
Ethics committee address [1] 309795 0
Ethics committee country [1] 309795 0
Australia
Date submitted for ethics approval [1] 309795 0
19/02/2021
Approval date [1] 309795 0
22/07/2021
Ethics approval number [1] 309795 0
2021/ETH00169

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 115414 0
Prof Phillip Stricker
Address 115414 0
St. Vincent's Private Clinic, Level 10/438 Victoria St, Darlinghurst NSW 2010
Country 115414 0
Australia
Phone 115414 0
+61283826971
Fax 115414 0
Email 115414 0
phillip@stricker.com.au
Contact person for public queries
Name 115415 0
Shikha Agrawal
Address 115415 0
St. Vincent's Private Clinic 438 Victoria St, Darlinghurst NSW 2010
Country 115415 0
Australia
Phone 115415 0
+61 402901143
Fax 115415 0
Email 115415 0
s.agrawal@garvan.org.au
Contact person for scientific queries
Name 115416 0
James Thompson
Address 115416 0
St. Vincent's Private Clinic Level 9/438 Victoria St, Darlinghurst NSW 2010
Country 115416 0
Australia
Phone 115416 0
+61 2 8046 8050
Fax 115416 0
Email 115416 0
drjethompson@gmail.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Aggregate de-identified 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
SourceTitleYear of PublicationDOI
Embase68Ga-PSMA-PET/CT in addition to mpMRI in men undergoing biopsy during active surveillance for low- to intermediate-risk prostate cancer: study protocol for a prospective cross-sectional study.2023https://dx.doi.org/10.21037/tau-22-708
N.B. These documents automatically identified may not have been verified by the study sponsor.