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Trial registered on ANZCTR


Registration number
ACTRN12618001640291
Ethics application status
Approved
Date submitted
26/09/2018
Date registered
4/10/2018
Date last updated
18/07/2019
Date data sharing statement initially provided
18/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Prospective trial assessing the additive diagnostic value of 68Ga-PSMA positron emission tomography (PSMA-PET) in men scheduled to undergo diagnostic biopsy for suspicion of prostate cancer.
Scientific title
Additive diagnostic value of prostate specific membrane antigen (PSMA) positron emission tomography (PET) to multiparametric magnetic resonance imaging (mpMRI) in the diagnostic setting: Ability to reduce unnecessary prostate biopsies in men being investigated for prostate cancer.
Secondary ID [1] 296180 0
Nil known
Universal Trial Number (UTN)
U1111-1221-1342
Trial acronym
PRIMARY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 309807 0
Condition category
Condition code
Surgery 308604 308604 0 0
Other surgery
Cancer 308615 308615 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A single pre-biopsy pelvic gallium 68 prostate specific membrane antigen positron emission tomography (68Ga-PSMA PET) will be performed, 68Ga-PSMA (H-BED CC-11) 2.0mbq/kg will be administered. A limited field of view PSMA PET of the pelvis (6 minutes/bed stop) will be undertaken a minimum 60 minutes post injection with a non-contrast-enhanced CT scan (pelvis) performed 60 minutes post tracer injection using the following CT parameters: 2 mm slice thickness soft tissue reconstruction kernel, 120 keV and 50 mAs, pitch of 0·828, 600 mm FOV and a 512 matrix and interpreted by specialist nuclear medicine physicians at a centralised location (Sydney - St Vincent's Public Hospital, Melbourne - Peter MacCallum Cancer Centre). This will occur within 8 weeks of initial referral for investigation of prostate cancer, prior to a template transperineal biopsy. The mpMRI will also occur prior to biopsy, and can occur before or after the PSMA PET.
Intervention code [1] 312508 0
Early detection / Screening
Intervention code [2] 312561 0
Diagnosis / Prognosis
Comparator / control treatment
Historical and in group gold-standard diagnostics (currently consisting of mpMRI, PSA, DRE and MRI targeted biopsy) will be compared to the addition of the PSMA and PSMA targeted biopsies.
Control group
Active

Outcomes
Primary outcome [1] 307571 0
Additive diagnostic value of PSMA PET with mpMRI in detecting significant cancer (defined as a core containing Gleason grade 3+4 disease or greater, with greater than 5% HG or greater than or equal to 15% single core or greater than or equal to 7mm PCa in any core) in men undergoing initial biopsy for suspicion of prostate cancer.
Timepoint [1] 307571 0
at completion of biopsy, within 8 weeks of initial referral for investigation
Primary outcome [2] 307578 0
Proportion of men who could have avoided biopsy with positive mpMRI (PI-RADS greater than or equal to 3) but negative PSMA and no clinically significant cancer was detected
Timepoint [2] 307578 0
at completion of biopsy, within 8 weeks of initial referral for investigation
Secondary outcome [1] 352308 0
Proportion of men who had clinically significant cancer detected only by positive PSMA, i.e. mpMRI PI-RADS less than or equal to 2
Timepoint [1] 352308 0
At completion of biopsy, within 8 weeks of initial referral for investigation
Secondary outcome [2] 352309 0
Proportion of men who had clinically significant cancer detected only by template biopsy, i.e. negative PSMA and mpMRI PI-RADS less than or equal to 2
Timepoint [2] 352309 0
At completion of biopsy, within 8 weeks of initial referral for investigation
Secondary outcome [3] 352310 0
Comparison of index lesion identification by template biopsies vs targeted lesions identified on mpMRI or PSMA. i.e. highest gleason grade group lesion identified on template biopsy vs targeted biopsies
Timepoint [3] 352310 0
At completion of biopsy, within 8 weeks of initial referral for investigation
Secondary outcome [4] 352314 0
In the subset of men proceeding to radical prostatectomy anatomic concordance of identified lesions on mpMRI and PSMA
Timepoint [4] 352314 0
Following radical prostatectomy, within 8 weeks of biopsy confirmed prostate cancer.

Eligibility
Key inclusion criteria
•Male, aged 18 years or over
•Suspicion or prostate cancer with either an abnormal DRE OR PSA greater than age specific reference range on two or more occasions
•No previously diagnosed prostate cancer
•No previous prostate biopsies
•Has undergone an mpMRI within the last 6 months, or scheduled to undergo an mpMRI prior to biopsy
•Ability to give written informed consent, participate in and comply with the study
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
• Previous diagnosis of PCa
• Previous prostate biopsies
• Inability/ incapacity to provide own consent
• PSA >20ng/ml
• greater than or equal to cT3 on DRE
• Contraindication to MRI, including but not restricted to:
o Pacemaker or other electronic implant
o Allergy or contraindiation to MRI contrast, e.g. renal failure (eGFR <30mL/min)
o Shrapnel, tattoos, non-removable body piercings (relative contraindication)

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
- Initial study to determine specificity and positive predictive value will require a sample size of 200
Formulas:
n=(ZxZ) x P(1-P)/(exe) (single proportion sample size formula)
Z = value from standard normal distribution corresponding to desired confidence level (Z=1.96 for 95% CI)
P is expected true proportion
e is desired precision (half desired CI width).
[n will be (a+c) if we use Sensitivity as P, and n will be (b+d) if we use Specificity as P in formula (1)]
N= (a+c)/Prevalence
N= (b+d)/(1-Prevalence)
Calculations:
Expected Sensitivity of 0.94, for ISUP 2 or above disease
Expected Specificity of 0.97, for ISUP 2 or above disease
Expected prevalence of 0.69
Desired precision of 0.05
If P is ‘Sensitivity’
n=(1.96)(1.96) x (0.94)(1-0.94)/(0.05)(0.05)=86.66
N=86.66/0.69=126
If P is ‘Specificity’
n=(1.96)(1.96) x (0.97)(1-0.97)/(0.05)(0.05)=44.71
N=44.71/(1-0.69)=145
Given that PPV and NPV are derived from the same values as specificity and sensitivity, it can be reasoned that the required sample size to achieve a power of 95% and p=0.05 will not exceed the maximal calculated sample size of 145.

- Option to extend study if early analysis shows an improvement in negative predictive value (power calculation for NPV – 578 patients)

Further power calculations are ongoing.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
19/07/2019
Actual
Date of last participant enrolment
Anticipated
2/03/2020
Actual
Date of last data collection
Anticipated
30/06/2020
Actual
Sample size
Target
200
Accrual to date
0
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 12004 0
St Vincent's Private Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [2] 12005 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [3] 12006 0
St George Hospital - Kogarah
Recruitment hospital [4] 12007 0
Epworth Freemasons - Melbourne
Recruitment hospital [5] 12008 0
Sydney Adventist Hospital - Wahroonga
Recruitment hospital [6] 12009 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [7] 12010 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 24163 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 24164 0
2217 - Kogarah
Recruitment postcode(s) [3] 24165 0
3002 - Melbourne
Recruitment postcode(s) [4] 24166 0
2076 - Wahroonga
Recruitment postcode(s) [5] 24167 0
2065 - St Leonards
Recruitment outside Australia
Country [1] 20870 0
Netherlands
State/province [1] 20870 0

Funding & Sponsors
Funding source category [1] 300770 0
Charities/Societies/Foundations
Name [1] 300770 0
St Vincent's Clinic Foundation Grant
Country [1] 300770 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital
Address
390 Victoria St, Darlinghurst NSW 2010
Country
Australia
Secondary sponsor category [1] 300314 0
Other Collaborative groups
Name [1] 300314 0
Garvan Institute of Medical Research
Address [1] 300314 0
384 Victoria St, Darlinghurst NSW 2010
Country [1] 300314 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301553 0
St Vincent's Hospital Sydney Human Research Ethics Committees
Ethics committee address [1] 301553 0
Ethics committee country [1] 301553 0
Australia
Date submitted for ethics approval [1] 301553 0
28/09/2018
Approval date [1] 301553 0
28/11/2018
Ethics approval number [1] 301553 0
HREC/18/SVH/239

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

Contacts
Principal investigator
Name 87362 0
A/Prof Louise Emmett
Address 87362 0
St Vincent's Hospital Theranostics and Nuclear Medicine Department
Level 2, Xavier Building, 390 Victoria St, Darlinghurst NSW 2010
Country 87362 0
Australia
Phone 87362 0
+61 02 8382 1815
Fax 87362 0
Email 87362 0
Louise.Emmett@svha.org.au
Contact person for public queries
Name 87363 0
Amer Amin
Address 87363 0
Garvan Institute of Medical Research
384 Victoria Street Darlinghurst NSW 2010
Country 87363 0
Australia
Phone 87363 0
+61 02 9355 5790
Fax 87363 0
Email 87363 0
a.amin@garvan.org.au
Contact person for scientific queries
Name 87364 0
Amer Amin
Address 87364 0
Garvan Institute of Medical Research
384 Victoria Street Darlinghurst NSW 2010
Country 87364 0
Australia
Phone 87364 0
+61 02 9355 5790
Fax 87364 0
Email 87364 0
a.amin@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
Individual participant data will be de-identified and pooled to ensure anonymity of participants.
Only group data will be used in any analysis and publications arising from this trial.


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
EmbaseTumour Heterogeneity and Resistance to Therapy in Prostate Cancer: A Fundamental Limitation of Prostate-specific Membrane Antigen Theranostics or a Key Strength?.2019https://dx.doi.org/10.1016/j.eururo.2019.07.030
EmbaseProtocol for the PRIMARY clinical trial, a prospective, multicentre, cross-sectional study of the additive diagnostic value of gallium-68 prostate-specific membrane antigen positron-emission tomography/computed tomography to multiparametric magnetic resonance imaging in the diagnostic setting for men being investigated for prostate cancer.2020https://dx.doi.org/10.1111/bju.14999
N.B. These documents automatically identified may not have been verified by the study sponsor.