Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001728820
Ethics application status
Approved
Date submitted
3/11/2021
Date registered
17/12/2021
Date last updated
17/12/2021
Date data sharing statement initially provided
17/12/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
To determine whether use of Technetium99m-labelled PSMA improves the sensitivity for detection and aids intra-operative localisation of lymph node metastases in men with intermediate or high-risk localised prostate cancer undergoing robotic-assisted radical prostatectomy.
Scientific title
Radioguided Surgery With Technetium99m-labelled PSMA To Aid Intra-operative Lymph Node Metastases Detection For Patients Undergoing Robotic-assisted Radical Prostatectomy (RARP) For Prostate Cancer.
Secondary ID [1] 305720 0
nil known
Universal Trial Number (UTN)
none
Trial acronym
DETECT TRIAL
Linked study record
none

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer with lymph node metastases 324189 0
Condition category
Condition code
Cancer 321671 321671 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be recruited at the St. Vincent's Prostate Cancer Research Centre with high-intermediate and high-risk cancer patients with a greater than or equal to 10% probability of LN involvement, where radical prostatectomy and ePLND would currently be performed as part of standard of care treatment (guided by the updated Briganti nomogram).

The nuclear medicine physicians will be in charge of administration of the Tc-PSMA radiopharmaceutical. On the day prior to surgery at approximately 3-4pm, 500MBq of Tc-PSMA will be intravenously administered to the patient at St Vincent’s Hospital in the nuclear medicine department. After a period of observation, patients will be allowed to return home, and then present for their procedure the next day.

On the day of surgery, Radioguided surgery for lymph node metastases will involve use of a robot-assisted drop-in gamma detection probe connected to a gamma detection device (Navigator GPSTM Control Unit), which will be able to provide visual and acoustic feedback gamma count levels.
Intervention code [1] 322109 0
Treatment: Devices
Intervention code [2] 322111 0
Treatment: Drugs
Comparator / control treatment
no control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 329444 0
To evaluate the feasibility of radioguided surgery using Tc-PSMA injection to aid intra-operative localisation and resection of lymph nodes at time of extended pelvic lymph node dissection during RARP
Timepoint [1] 329444 0
Data collection of the number of lymph nodes removed noted in a specified study data collection form and medical records. Also, determined from histopathology report received 24-48 hours post surgery
Primary outcome [2] 329813 0
To evaluate the safety of radioguided surgery using Tc-PSMA injection to aid intra-operative localisation and resection of lymph nodes at time of extended pelvic lymph node dissection during RARP
Timepoint [2] 329813 0
up to 7 days post surgery as per standard of care, the patient stays as an inpatient in the hospital
Safety assessment is determined on follow-up visit data collection form when assessing adverse events and noted in the medical records as per standard of care.
Secondary outcome [1] 402643 0
To evaluate the diagnostic accuracy of radio-guided surgery with Tc-PSMA injection in detecting small nodal metastases (<4-5mm) in-vivo and ex-vivo by comparing probe results with final pathology after extended pelvic lymph node dissection
Timepoint [1] 402643 0
Determined from histopathology report received 24-48 hours post surgery and compared with data collected during surgery
Secondary outcome [2] 403939 0
To evaluate the quality of life after radioguided surgery using Tc-PSMA by used of validated questionaires (EPIC/IPSS)
Timepoint [2] 403939 0
assessed Baseline and 6 weeks, 3 months, 6 months, 12 months, 24 months and 36 months (post surgery)

Eligibility
Key inclusion criteria
Patients must meet the following inclusion criteria to be eligible to participate in the study:
• Male, aged 18 years or over
• Confirmed adenocarcinoma of prostate and at least clinical stage T3A and/or Gleason sum greater than or equal to 4+3=7, or preoperative PSA greater than or equal to 15 ng/ml and planned radical prostatectomy
• Suspected lymph node involvement pre- radical prostatectomy based on Briganti nomogram greater than or equal to 10%.
• Had a prior 68Ga-PSMA PET Scan prior to surgery within 90 days prior to surgery with greater than or equal to 1 lymph node with suspicion for metastases
• Suitable for radical prostatectomy and pelvic lymph node dissection, as per institutional guidelines and not yet treated (pre-prostatectomy)
• Subject is able to understand and willing to sign the participant information statement and consent form
• Subject is expected to remain available for 24 months of clinic visits
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who meet any of the following exclusion criteria are not eligible to participate in the study:
• Past history any other type of cancer (except skin cancer).
• Previous treatment for PCa (surgery, radiotherapy, chemotherapy, hormone androgen deprivation therapy)
• Proven bony metastatic disease, visceral metastases or lymph node metastases above the level of the aortic bifurcation (ie unequivocal evidence of disease outside the pelvis on conventional imaging)
• Previous surgery in pelvis that may limit the extent of PLND (as per assessment by surgeon)
• Patients who refuse radical prostatectomy or PLND
• Patients who refuse to join the trial or are unable to consent
• Patients not being considered for further therapy
• Contra-indication to PSMA-PET scanning or allergy to other injectable contrast media used in this trial
• Patients who cannot lie still for at least 30 minutes or comply with imaging
• Subject has medical conditions that would limit study participation (per physician discretion)
• Subject is enrolled in one or more concurrent studies that would confound the study results of this study as determined by the study investigators
• Subject has a limited life expectancy that would not allow completion of the 24 month visits

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)
none
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
none
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Variables including PSMA positivity and lymph node positivity will be dichotomised on a per patient and per region basis.
Diagnostic performance will be assessed on a per patient basis for 68Ga-PSMA vs Tc-PSMA guided positive nodes and compared with histopathology as the reference standard. 2x2 Tables will be constructed for 68Ga-PSMA vs histopathology and Tc-PSMA vs histopathology. Sensitivity, specificity, PPV and NPV will be derived for each group, then compared using the McNemar test for significance of difference between estimates.
Confidence intervals (CIs) for differences in sensitivities will be calculated using the method proposed by Tango (1998).
(Tango T. Equivalence test and confidence interval for the difference in proportions for the paired-sample design. Statistics in medicine. 1998;17(8):891-908.)

Analysis will also be performed on a per region basis, with each patient’s imaging and histopathology divided into 6 regions on PSMA and lymphadenectomy (left external iliac/internal iliac/obturator and right external iliac/internal iliac/obturator regions). This will give 120 regions for 2x2 table analysis.

Binary logistic regression and AUC analysis will be performed to explore the relationship between pre-operative 68Ga-PSMA and Tc-PSMA SUV counts, intra-operative Tc-gamma counts and the presence of cancer on histopathology, using a generalized estimating equation to adjust for correlation between different regions within one patient. P-values <0.05 will be considered significant. All p-values will be two-tailed. All analyses will be performed using SAS 9.4 Statistical Software and SPSS.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
26/06/2019
Date of last participant enrolment
Anticipated
30/12/2022
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
20
Accrual to date
12
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 21013 0
St Vincent's Private Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 35848 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 310077 0
Hospital
Name [1] 310077 0
St. Vincent's Prostate Cancer Research Centre
Country [1] 310077 0
Australia
Primary sponsor type
Hospital
Name
St. Vincent's Prostate Cancer Research Centre
Address
St Vincent's Clinic
Level 10/438 Victoria St,
Darlinghurst NSW 2010
Country
Australia
Secondary sponsor category [1] 311132 0
None
Name [1] 311132 0
Address [1] 311132 0
Country [1] 311132 0
Other collaborator category [1] 282057 0
Other
Name [1] 282057 0
The Garvan Institute of Medical Research
Address [1] 282057 0
384 Victoria St, Darlinghurst NSW 2010
Country [1] 282057 0
Australia
Other collaborator category [2] 282058 0
Hospital
Name [2] 282058 0
St. Vincent's Hospital
Address [2] 282058 0
370 Victoria street
Darlinghurst NSW 2010
Country [2] 282058 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309768 0
St Vincent's Health Network; St Vincent's Hospital Human Research Ethics Committee.
Ethics committee address [1] 309768 0
St Vincent’s Health Network
Translational Research Centre
97-105 Boundary Street
Darlinghurst, NSW 2010
Ethics committee country [1] 309768 0
Australia
Date submitted for ethics approval [1] 309768 0
23/05/2016
Approval date [1] 309768 0
01/09/2016
Ethics approval number [1] 309768 0
HREC/16/SVH/157

Summary
Brief summary
The purpose of this study is to determine whether it is feasible and safe to use Technetium99m-labelled PSMA as a tracer during prostate removal surgery (or a 'radical prostatectomy') for men with prostate cancer.

Who is it for?
You may be eligible for this study if you are an adult male, who has been diagnosed with prostate cancer and is scheduled to receive a radical prostatectomy.

Study details
All participants will be asked to come into the hospital around 3-4pm the day before the surgery to receive an injection of the tracer and a scan. Once they have received the tracer, they will be observed for a while before going home.

All participants will then proceed with the surgery as planned the next day.

It is hoped that this study will be able to determine whether using Technetium99m-labelled PSMA as a tracer during radical prostatectomy is safe and results in better detection of any cancer that may have spread.

Follow-up visits
To determine the outcome of treatment, the participant will be asked to complete the self-reporting Expanded Prostate Cancer Index Composite (EPIC) survey. The EPIC survey has been extensively used to report on the physical, emotional and psychological outcomes of prostate cancer. The questionnaires will be completed at baseline (prior to surgery), at 6 weeks, 3 months, 6 months, 1 year and then yearly for a minimum of 3-5 years

Trial website
none
Trial related presentations / publications
none
Public notes

Contacts
Principal investigator
Name 115322 0
Prof Phillip Stricker
Address 115322 0
St Vincent's Clinic
Level 10/438 Victoria St,
Darlinghurst NSW 2010
Country 115322 0
Australia
Phone 115322 0
+61 2 83826971
Fax 115322 0
Email 115322 0
[email protected]
Contact person for public queries
Name 115323 0
Mrs Shikha Agrawal
Address 115323 0
The Garvan Institute of Medical Research
The Kinghorn Cancer Centre Building
Level 6, 370 Victoria street
Darlinghurst NSW 2010
Country 115323 0
Australia
Phone 115323 0
+61 2 9355 5735
Fax 115323 0
Email 115323 0
[email protected]
Contact person for scientific queries
Name 115324 0
Dr William Gondoputro
Address 115324 0
The Garvan Institute of Medical Research
The Kinghorn Cancer Centre Building
Level 6, 370 Victoria street
Darlinghurst NSW 2010
Country 115324 0
Australia
Phone 115324 0
+61 425104368
Fax 115324 0
Email 115324 0
[email protected]

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
Current Study Results
No documents have been uploaded by study researchers.

Update to Study Results
Doc. No.TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
4815Study results articleYes Gondoputro W, Blazevski A, Amin A, Scheltema M, Ag... [More Details]

Documents added automatically
No additional documents have been identified.