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Trial registered on ANZCTR


Registration number
ACTRN12624001245583p
Ethics application status
Submitted, not yet approved
Date submitted
24/09/2024
Date registered
10/10/2024
Date last updated
10/10/2024
Date data sharing statement initially provided
10/10/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
SUBDUE-3: A Phase 0 study of SUB-urothelial DUrvalumab-Zirconium to investigate local and systemic distribution of Durvalumab when injected in the sub-urothelium in adult subjects with muscle invasive bladder cancer or high-risk non-muscle invasive bladder tumours.
Scientific title
SUBDUE-3: A Phase 0 study of SUB-urothelial DUrvalumab-Zirconium to investigate local and systemic distribution of Durvalumab when injected in the sub-urothelium of adult subjects with muscle invasive bladder cancer or high-risk non-muscle invasive bladder cancer
Secondary ID [1] 313042 0
ANZUP 2402
Universal Trial Number (UTN)
Trial acronym
SUBDUE-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Muscle invasive or high risk non muscle invasive bladder cancer 335266 0
Condition category
Condition code
Cancer 331835 331835 0 0
Bladder

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Dose: 25mls of 89Zr-Durvalumab constituted as:
a)37 Megabecquerels (MBq) in 4mg of Durvalumab in 4mls of 0.9% saline, combined with
b)21mg of Durvalumab in 21mls of 0.9% saline

Duration: Single administration of 89Zr-Durvalumab constituted as prescribed dose. The prescribed dose is administered during flexible cystoscopy two weeks prior to cystectomy. Patients will subsequently have 4 PETCT scans and blood tests over 1 week to determine the local and systemic distribution of 89Zr-durvalumab when injected in the sub-urothelium

Mode: 25 sub-urothelial 1ml injections distributed evenly across the bladder, including the trigone. Injected in 1mL aliquots throughout the bladder under general anaesthesia using a a 5Fr Bonee needle via a 22Fr rigid cystoscope followed by urethral catheterisation prior to cystectomy.

Subsequent PET imaging will be obtained at:
a) 1-3 hours (bladder only)
b) 24 hours (whole body and dedicated pelvic scan)
c) 72 hours (whole body)
d) 5-7 days (whole body)

Blood sampling will be undertaken along with the imaging time point to evaluate for systemic 89Zr-durvalumab bioavailibity using a gamma counter.

The urinary catheter bag will be sent to medical physics at the time of first imaging to calculate the urinary radiation dose, and the catheter will be removed following the first scan.
Intervention code [1] 329594 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 339457 0
Composite primary outcome of visual and semi-quantitative assessment of 89Zr-Durvalumab PET over multiple timepoints to assess local (bladder wall) and systemic (liver, kidney, lung, bone marrow) distribution following sub-urothelial administration.
Timepoint [1] 339457 0
PET imaging obtained at:
a) 1-3 hours (bladder only) post injection of 89Zr-Durvalumab
b) 24 hours (whole body and dedicated pelvic scan) post injection of 89Zr-Durvalumab
c) 72 hours (whole body) post injection of 89Zr-Durvalumab
d) 5-7 days (whole body) post injection of 89Zr-Durvalumab

Blood sampling will be undertaken along with the imaging time point to evaluate for systemic 89Zr-durvalumab bioavailibity using a gamma counter.

The urinary catheter bag will be sent to medical physics at the time of first imaging to calculate the urinary radiation dose, and the catheter will be removed following the first scan.
Secondary outcome [1] 440050 0
Safety of suburothelial 89Zr-durvalumab administration
Timepoint [1] 440050 0
Screening will take place anytime between 28 days to 1 day pre-cystoscopy and durvalumab injection). Serum blood tests will be taken once during the screening period for Hepatitis B and C and HIV serology, CMP, FBP, UEC, LDH, TFTs, LFTs, glucose, cortisol, and coagulation profile.

PET imaging will be obtained at:
a) 1-3 hours (bladder only) post injection of 89Zr-Durvalumab
b) 24 hours (whole body and dedicated pelvic scan) post injection of 89Zr-Durvalumab
c) 72 hours (whole body) post injection of 89Zr-Durvalumab
d) 5-7 days (whole body) post injection of 89Zr-Durvalumab

Blood sampling will be undertaken at each imaging time point above to evaluate for systemic 89Zr-durvalumab bioavailibity using a gamma counter.

The urinary catheter bag will be sent to medical physics at the time of first imaging to calculate the urinary radiation dose, and the catheter will be removed following the first scan.

At each imaging timepoint mentioned above the patient will be questioned about adverse events.

Day of cystectomy: the patient will be questioned about adverse events..
2 weeks post cystectomy: the patient will be questioned about adverse events.

Histopathology of the radical cystectomy will be assessed to determine any local adverse events within 2 weeks of radical cystectomy

Eligibility
Key inclusion criteria
Study population: Participants with either muscle invasive bladder cancer or high-risk non-muscle invasive (T1, high grade Ta, carcinoma in-situ) bladder tumours scheduled for cystectomy,

Inclusion criteria:
• Capable of giving signed informed consent.
• Willingness to undergo the described procedure and study schedule of investigations
• Age greater than or equal to 18 years.
• Have either MIBC or high-risk NMIBC (T1, high-grade Ta, carcinoma in situ) scheduled for radical cystectomy (including neo-adjuvant chemotherapy).
• ECOG performance status of less than 2.
• Life expectancy of greater than or equal to 6 months.
• Adequate organ and marrow function.
Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:
• Concurrent cancer therapy with the same biological intent that may interact with durvalumab. Neo-adjuvant chemotherapy allowed.
• Any unresolved toxicity NCI CTCAE (version 5.0) Grade greater than or equal to 2 from previous anticancer therapy.
• Major surgical procedure within 28 days prior to administration of durvalumab.
• History of allogeneic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders.
• History of active primary immunodeficiency.
• Active tuberculosis, hepatitis B, hepatitis C.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab
• Receipt of live attenuated vaccine within 30 days prior to administration of durvalumab. Patients should not receive live vaccine up to 30 days after durvalumab administration
• Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab.
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
• Prior randomisation or treatment in a previous durvalumab or other immunotherapy clinical study.
• Previous administration of any radionuclide within 10 half-lives of the same

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
Other design features
Phase
Phase 0
Type of endpoint/s
Bio-availability
Statistical methods / analysis
As a phase 0 pilot study, a sample size of 3 is considered feasible and pragmatic to assess feasibility and preliminary safety in the first instance. Recruitment is anticipated to occur over 6 months. Given the sample size, analyses of adverse events, patient reported outcomes and translational data will be reported using descriptive statistics.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
7/12/2024
Actual
Date of last participant enrolment
Anticipated
9/09/2025
Actual
Date of last data collection
Anticipated
22/12/2025
Actual
Sample size
Target
3
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 27146 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 43224 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 317483 0
Other Collaborative groups
Name [1] 317483 0
Australian and New Zealand Urogential and Prostate (ANZUP) Cancer Trials Group
Country [1] 317483 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australian and New Zealand Urogential and Prostate (ANZUP) Cancer Trials Group
Address
Country
Australia
Secondary sponsor category [1] 319775 0
None
Name [1] 319775 0
Address [1] 319775 0
Country [1] 319775 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 316197 0
South Metropolitan Health Service Human Research Ethics Committee
Ethics committee address [1] 316197 0
Ethics committee country [1] 316197 0
Australia
Date submitted for ethics approval [1] 316197 0
10/09/2024
Approval date [1] 316197 0
Ethics approval number [1] 316197 0

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

Contacts
Principal investigator
Name 137106 0
Prof Dickon Hayne
Address 137106 0
Fiona Stanley Hospital 11 Robin Warren Drive Murdoch WA 6150
Country 137106 0
Australia
Phone 137106 0
+61 08 61511130
Fax 137106 0
Email 137106 0
Dickon.Hayne@uwa.edu.au
Contact person for public queries
Name 137107 0
Kevin Keane
Address 137107 0
Fiona Stanley Hospital 11 Robin Warren Drive Murdoch WA 6150
Country 137107 0
Australia
Phone 137107 0
+61 08 6152 2222
Fax 137107 0
Email 137107 0
kevin.keane@health.wa.gov.au
Contact person for scientific queries
Name 137108 0
Dickon Hayne
Address 137108 0
Fiona Stanley Hospital 11 Robin Warren Drive Murdoch WA 6150
Country 137108 0
Australia
Phone 137108 0
+61 08 6152 2222
Fax 137108 0
Email 137108 0
Dickon.Hayne@uwa.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.