Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000073606
Ethics application status
Approved
Date submitted
12/01/2023
Date registered
23/01/2023
Date last updated
23/01/2023
Date data sharing statement initially provided
23/01/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A Single-Arm, Open-Label, Prospective, Phase 0 Trial Evaluating the Safety and Efficacy of Salvage 177Lu-PSMA-I&T in Prostate Specific Antigen (PSA) Biochemical Failure After Radical Prostatectomy for High-Risk Prostate Cancer
Scientific title
A Single-Arm, Open-Label, Prospective, Phase 0 Trial Evaluating the Safety and Efficacy of Salvage 177Lu-PSMA-I&T in Prostate Specific Antigen (PSA) Biochemical Failure After Radical Prostatectomy for High-Risk Prostate Cancer
Secondary ID [1] 308749 0
None
Universal Trial Number (UTN)
U1111-1287-0155
Trial acronym
SLAP trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate cancer
 328693 0
Condition category
Condition code
Cancer 325702 325702 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Investigational drug: 177Lutetium-PSMA-I&T
Mechanism: Radioligand targeted therapy
Class: Radiopharmaceutical (theranostic)

Dose: 7.5GBq of 177Lu-PSMA-I&T (+/- 5%)
Dose volume: 10ml
Number of doses and duration: Single cycle (ie. 1x dose for the duration of the study)
Mode of delivery: Intravenous Infusion Duration

The timing of drug infusion relative to post-radical prostatectomy is variable but within 4 weeks of identifying PSA biochemical failure. (The first PSA testing is normally conducted at their 6-week follow-up)

Monitoring for drug adherence is not applicable (single dose for the duration of the study)

Record of treatment administration and subsequent biochemistry will be recorded on the hospital's electronic medical record.
Intervention code [1] 325208 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 333556 0
The primary objective is to determine the serum PSA response following a single cycle of 177Lu-PSMA-I&T at 3-months in men with undetectable PSA biochemical failure after radical prostatectomy.
Timepoint [1] 333556 0
The primary time point for each participant will be at 3-months post-administration intravenous 177Lu-PSMA-I&T.

Subsequent serial PSA monitoring will occur quarterly for at least 36-months post-administration intravenous 177Lu-PSMA-I&T.
Secondary outcome [1] 417500 0
Adverse events following administration of a single cycle of 177Lu-PSMA-I&T

At each follow-up timepoint. Participants will be asked a series of health-related questions from a study-specific questionnaire and undergo a general clinical examination (head and neck, chest, abdominal. A more focused examination may also be conducted depending on their health-related responses). All biochemistry is also monitored at each timepoint.

Questionaire and examination data is kept on a secure password protect hospital server (backed up every 24hrs). Biochemistry results are kept on the hospital's electronic medical record

Less Common Possible Side Effects (1-10%)
- Increased creatinine indicating a possible effect on your kidneys
-Fever associated with reduced white cells
-Anxiety
-Depression
-Confusion
-Reduction in the number of red blood cells
-Headaches
-Memory loss
-Abdominal pain
-Weakness
-Irregular heartbeat
-Chest pain
-Dry mouth
-Flu-like symptoms
-Indigestion
-Blood in urine
-Nose bleeds

Common Possible Side Effects (>10%)
-Reduction in white blood cells which could increase the likelihood of bleeding
-Reduction in white blood cells making it more difficult to fight infection
-Reaction at the site of infusion
-Feeling tired
-Weight loss
-Nausea
-Localised pain
-Joint pain
-Shortness of breath
-Loss of appetite
-Swelling in your limbs
-Constipation
-Diarrhea
-Insomnia
-Increased urination
-Cough
-Increased levels of liver enzymes
-Dry mouth
Timepoint [1] 417500 0
Adverse events for each patient will be assessed at 30-days, then at 3-months and then on a quarterly basis for at least 36-months following administration of a single cycle of 177Lu-PSMA-I&T
Secondary outcome [2] 417502 0
Health Related Quality of Life using the Extended Prostate Cancer Index Survey (EPIC-26).
Timepoint [2] 417502 0
EPIC-26 questionnaire will be completed by each participant at 30-days, then at 3-months, 6-months, 12-months, 18-months, 24-months, 36-months post-administration intravenous 177Lu-PSMA-I&T.
Secondary outcome [3] 417503 0
Time to commence androgen deprivation therapy (ADT).

This will depend on the PSA trend and is a multidisciplinary decision. A rising PSA will prompt the investigator to represent the participant at a multidisciplinary meeting and determine if ADT should be commenced. This is the standard of care pathway for decision-making in men with biochemical failure.

Serial PSA monitoring is outlined in the primary timepoint. PSA results are available on the participant's medical record.
Timepoint [3] 417503 0
Time to commencing ADT is dependent on PSA response and will be assessed at 30-days, then at 3-months, and then on a quarterly basis for at least 36-months following administration of a single cycle of 177Lu-PSMA-I&T.
Secondary outcome [4] 417504 0
Time to radiological progression.

This will be assessed by PSMA-PET/CT imaging to determine if there is evidence of radiological progression. Imaging will be conducted onsite at our radiology department and data will be available on hospital's electronic medical record

Obtaining progress imaging is at the discretion of a multidisciplinary team decision and is dependent on the PSA trend. A rising PSA will prompt the investigator to represent the participant at a multidisciplinary meeting and determine if repeat imaging should be performed. This is the standard of care pathway for decision-making in men with biochemical failure.
Timepoint [4] 417504 0
Time to commencing ADT is dependent on PSA response and will be assessed at 30-days, then at 3-months, and then on a quarterly basis for at least 36-months following administration of a single cycle of 177Lu-PSMA-I&T.
Secondary outcome [5] 417660 0
Determine the proportion of subjects in whom PSA levels fall below pre-treatment levels,
Timepoint [5] 417660 0
Baseline PSA is always available prior to radical prostatectomy and will be used to compare PSA results at 3-months, and then quarterly for at least 36-months post-administration intravenous 177Lu-PSMA-I&T.


Eligibility
Key inclusion criteria
• Men who have undergone radical prostatectomy for National Comprehensive Cancer Network high or very high-risk prostate cancer.
• Negative surgical margins on radical prostatectomy histopathology.
• PSA initially undetectable following radical prostatectomy.
• PSA biochemical failure – defined as greater than or equal to 0.20ng/mL
• PSMA expressing prostate cancer on pre-operative 18F-DCFPyL PSMA PET/CT
• 18F-DCFPyL PSMA PET/CT demonstrating no evidence of uptake to suggest detectable residual or metastatic disease
• No local recurrence on post-operative mpMRI
• No artifact disrupting interpretation of initial prostate cancer imaging
• Significant PSMA expressing tumour on initial staging
• Ability to give written informed consent, participate in and comply with study
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
• Previous diagnosis of prostate cancer
• Positive surgical margin on radical prostatectomy specimen pathology
• Non-PSMA expressing prostate cancer (e.g. ductal or neuroendocrine)
• Artifact disrupting interpretation of initial prostate cancer imaging (e.g. THR)
• Presence of suspected metastatic disease on pre-operative and post-operative 18F-DCFPyL PSMA PET/CT scan or mpMRI
• Undetectable serum testosterone
• Contraindication to Gadolinium
• Contraindication to 177Lu-PSMA therapy

Study design
Purpose of the study
Treatment
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
None
Phase
Phase 0
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
For the primary outcome, descriptive statistics will be provided for the cohort. The exploratory time-to-event endpoints will be estimated and represented using the Kaplan-Meier method.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/03/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 23824 0
Sydney Adventist Hospital - Wahroonga
Recruitment postcode(s) [1] 39278 0
2076 - Wahroonga

Funding & Sponsors
Funding source category [1] 312973 0
Self funded/Unfunded
Name [1] 312973 0
Each participant will self-fund their 177Lu-PSMA-I&T treatment (includes radiology staff, consumables, drug and imaging).
Country [1] 312973 0
Australia
Funding source category [2] 313023 0
Other
Name [2] 313023 0
In-kind support will be provided by study Investigators for follow-up for all participants of this study
Country [2] 313023 0
Australia
Primary sponsor type
Individual
Name
Dr Anthony-Joe Nassour
Address
Prostate Centre of Excellence, Sydney Adventist Hospital 185 Fox Valley Road, Wahroonga, NSW 2076
Country
Australia
Secondary sponsor category [1] 314711 0
Individual
Name [1] 314711 0
Dr Anthony-Joe Nassour
Address [1] 314711 0
Prostate Centre of Excellence, Sydney Adventist Hospital 185 Fox Valley Road, Wahroonga, NSW 2076
Country [1] 314711 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312241 0
Adventist HealthCare Limited (AHCL) Human Research Ethics Committee (HREC)
Ethics committee address [1] 312241 0
Sydney Adventist Hospital
185 Fox Valley Road, Wahroonga, NSW 2076
Ethics committee country [1] 312241 0
Australia
Date submitted for ethics approval [1] 312241 0
23/11/2022
Approval date [1] 312241 0
13/12/2022
Ethics approval number [1] 312241 0
AHCL Reference ID: 2022-036

Summary
Brief summary
This study aims to assess whether a single dose of 177 Lutetium-PSMA-targeted therapy is safe and effective as a treatment for men who have developed biochemical failure after having a radical prostatectomy.

Who is it for?
You may be eligible for this study if you are a male aged 18 years or older who has recently undergone a radical prostatectomy (surgery to remove the prostate) due to a diagnosis of high or very high risk prostate cancer. Participants will undergo blood tests and MR imaging to determine whether they meet the additional criteria of biochemical failure.

Study details
All participants who choose to enrol in this study will receive a single dose of 177 Lutetium-PSMA-targeted therapy that will be administered intravenously (through a vein). Please note that any participants who are eligible for this study will need to pay out-of-pocket for the study treatment (177-Lu-PSMA-I&T) as well as the post-operative mpMRI (multiparametric Magnetic Resonance Imaging of the prostate). It is anticipated that the single dose will be administered over a 10-minute period followed by a saline (neutral fluid) flush. Participants will then be asked to provide blood samples at 3 months post-dose, and then every 4 months for up to 3 years post-dose. Participants will also be asked to complete a questionnaire about their health at 30 days, and then every 3-6 months for up to 3 years post-dose. Additional imaging scans will also be collected at 3 months post-dose, with the potential for further imaging to be determined by the treating clinician.

It is hoped this research will determine whether a single dose of 177 Lutetium-PSMA-targeted therapy is safe and whether it has a positive impact on resistant prostate cancer. If this study does show that the drug is safe and effective, a larger study to examine potential benefits in more patients may proceed.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 123958 0
Prof Henrry Woo
Address 123958 0
Australian Clinical Trials Suite 406
San Clinic
185 Fox Valley Road, Wahroonga NSW 2076
Country 123958 0
Australia
Phone 123958 0
+61 2 9052 7586
Fax 123958 0
Email 123958 0
henry.woo@sah.org.au
Contact person for public queries
Name 123959 0
Dr Anthony-Joe Nassour
Address 123959 0
Sydney Adventist Hospital, Prostate Centre of Excellence
185 Fox Valley Road, Wahroonga, NSW 2076
Country 123959 0
Australia
Phone 123959 0
+61 405959444
Fax 123959 0
Email 123959 0
anthony-joe.nassour@sah.org.au
Contact person for scientific queries
Name 123960 0
Dr Anthony-Joe Nassour
Address 123960 0
Sydney Adventist Hospital, Prostate Centre of Excellence
185 Fox Valley Road, Wahroonga, NSW 2076
Country 123960 0
Australia
Phone 123960 0
+61 405959444
Fax 123960 0
Email 123960 0
anthony-joe.nassour@sah.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
Given the small sample size there is an intrinsic risk of a confidentiality breach if an IPD is provided. However, we anticipate this study will evolve into a larger randomised control trial where an IPD will be available.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
18039Study protocol    attachment 385225-(Uploaded-12-01-2023-23-00-11)-Study-related document.docx
18040Ethical approval    385225-(Uploaded-12-01-2023-23-00-11)-Study-related document.pdf
18041Informed consent form    385225-(Uploaded-20-01-2023-16-33-08)-Study-related document.pdf



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.