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Trial registered on ANZCTR


Registration number
ACTRN12621000411842
Ethics application status
Approved
Date submitted
29/01/2021
Date registered
15/04/2021
Date last updated
15/04/2021
Date data sharing statement initially provided
15/04/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A single-centre, open-label, phase I study to evaluate the diagnostic performance of 89Zirconium-labelled girentuximab (89Zr-TLX250) Position Emission Tomography (PET) in Urothelial Cancer Patients
Scientific title
A single-centre, open-label, phase I study to evaluate the diagnostic performance of 89Zirconium-labelled girentuximab (89Zr-TLX250) PET in Urothelial Cancer Patients
Secondary ID [1] 303274 0
Nil
Secondary ID [2] 303925 0
None
Universal Trial Number (UTN)
Trial acronym
ZipUP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic urothelial carcinoma 320467 0
Bladder cancer 320468 0
Condition category
Condition code
Cancer 318352 318352 0 0
Bladder

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients with histopathologically diagnosed bladder cancer or urothelial carcinoma already being staged with Fluorodeoxyglucose (FDG) PET/CT or those with known FDG positive metastatic disease, who are willing to undergo an additional 89Zr-TLX250 PET/CT for the staging and detection of urothelial carcinoma and bladder cancer.

89Zr-TLX250, a chimeric monoclonal antibody (INN name: girentuximab (GTX), synonyms: cG250, TLX250) with specificity for the CAIX (carbonic anhydrase 9) antigen, radiolabelled with the positron emitting radio-metal zirconium-89 via a NSuc-DFO-TFP-ester (DFO-TFP), linked to lysine residues of GTX, to yield 89Zr-DFO-TFP-GTX.

20 patients (10 patients with known metastatic urothelial carcinoma or bladder cancer and 10 patients who require primary staging of localized urothelial carcinoma or bladder cancer) will receive a single slow intravenous injection of 37 mBq (± 10%) 89Zr-TLX250, containing a mass dose of 10 mg of girentuximab over 3 minutes, followed by a diagnostic PET/CT scan on day 5 ± 2 days. Patients will be followed up at day 14 of post diagnostic 89Zr-TLX250 PET/CT scan.

The 89Zr-TLX250 IV administration will be administered by a trained nuclear medicine physician or a nuclear medicine technician (guided by a nuclear medicine physician).


The whole body 89Zr-TLX250 PET/CT will be acquired over a maximum of 45 minutes in 4 bed positions at a single time point on Day 5 ± 2 post administration of 89Zr-TLX250 using static image acquisition and low dose CT without contrast agent.
Intervention code [1] 319578 0
Diagnosis / Prognosis
Comparator / control treatment
The whole body FDG PET/CT scan will be acquired over a maximum of 45 minutes in 4 bed positions at screening (a single time point between 28 days and 1 day before the administration of 89Zr-TLX250 on Day 0) in line with routine site protocols. The FDG PET/CT scan will be performed under Standard of Care,
Control group
Active

Outcomes
Primary outcome [1] 326323 0
The feasibility of using 89Zr-TLX250 PET/CT as a diagnostic and staging tool in urothelial carcinoma and bladder cancer will be defined by the ability to recruit to the target sample size within the study duration. This reflects a willingness of clinicians to refer patients for this study and a willingness of patients to undergo 89Zr-TLX250 PET/CT as for diagnosis or staging.

To assess this outcome, all study records such as electronic Case Report Form data, imaging results, histopathology results, diagnostic performance (sensitivity, specificity, positive and negative predictive values, accuracy), and safety evaluation (standard laboratory, physical examination, 12-lead electrocardiogram, vital signs, and adverse events) will be monitored and audited.
Timepoint [1] 326323 0
Upon study completion of 18 months
Secondary outcome [1] 391063 0
Safety and tolerability:
• Baseline safety evaluations will be made within 28 days prior to 89Zr-TLX250 administration. This would include vital signs, standard laboratory (full blood count, renal function, basic electrolytes and liver function test), 12-lead ECG and concomitant medication recording.
• Vital signs will be recorded before and after administration of 89Zr-TLX250. 12-lead ECG and adverse event recording will be performed post administration.
• Safety evaluations will also be made at follow-up phone consult post PET/CT 14 days
Timepoint [1] 391063 0
Participant baseline safety outcome will be assessed within 28 days prior to 89Zr-TLX250 administration.

After post-intervention administration, outcome will be assessed daily for 14 days post intervention.
Secondary outcome [2] 391064 0
Effectiveness of 89Zr-TLX250 PET/CT vs FDG PET/CT in detecting metastatic or localized urothelial carcinoma and bladder cancer

- 89Zr-TLX250 tumour uptake will be qualitatively assessed, considering whether or not 89Zr-TLX250 binding is seen in lymph nodes or distant visceral organs.
Timepoint [2] 391064 0
This outcome will be assessed post analysis of histopathology collection after surgery.

Specifically, this outcome will be assessed after FDG PET./CT scan at screening, following 89Zr-TLX250 PET/CT scan (post intervention administration), and after follow-up of 14 days.
Secondary outcome [3] 391065 0
Sensitivity and specificity of 89Zr-TLX250 PET/CT vs FDG PET/CT in detecting lymph node metastases in urothelial carcinoma or bladder cancer.

PET/CT results will be correlated with pelvic lymphadenectomy histopathological findings in those undergoing radical cystectomy. Participants who are undergoing radical cystectomy are among the participants recruited for this study.
Timepoint [3] 391065 0
This timepoint is covered from screening (within 28 days of selection) to follow-up at Day 14 follow-up, or in those participants proceeding with surgery any time after 89Zr-TLX250 PET/CT imaging.

This outcome involves FDG imaging from screening through to the analysis of pelvic lymphadenectomy histopathological findings post surgery.
Secondary outcome [4] 392814 0
Effectiveness of 89Zr-TLX250 PET/CT vs FDG PET/CT in detecting metastatic urothelial carcinoma or bladder cancer.

-FDG tumour uptake will be qualitatively assessed, considering whether or not FDG binding is seen in lymph nodes or distant visceral organs.
Timepoint [4] 392814 0
Outcome will be assessed post FDG PET/CT at screening (28 days to day 0 of 89Zr-TLX250 administration), from day 0 89Zr-TLX250 administration to 89Zr-TLX250 PET/CT scan, and daily from 89Zr-TLX250 PET/CT scan to day 14 follow-up.
Secondary outcome [5] 392815 0
Effectiveness of 89Zr-TLX250 PET/CT vs FDG PET/CT in detecting metastatic urothelial carcinoma or bladder cancer.

Quantitative 89Zr-TLX250 vs FDG tumour targeting
Tumour vs mediastinal uptake ratio for 89Zr-TLX250 PET/CT and FDG PET/CT will be calculated and compared.
Timepoint [5] 392815 0
Outcome will be assessed post FDG PET/CT at screening (28 days to day 0 of 89Zr-TLX250 administration), from day 0 89Zr-TLX250 administration to 89Zr-TLX250 PET/CT scan, and daily from 89Zr-TLX250 PET/CT scan to day 14 follow-up.

Eligibility
Key inclusion criteria
1. Patients aged 18 or older with bladder cancer or urothelial carcinoma who are able to provide informed consent
2. Negative serum pregnancy test in female patients of childbearing potential at screening and consent to practise double-barrier contraception until a minimum of 42 days after 89Zr-TLX250 administration.
3. Histologically diagnosed with urothelial carcinoma or bladder cancer (or upper tract urothelial carcinoma diagnosed based on standard imaging and malignant urine cytology or direct visualisation on ureteroscopy) or known metastatic urothelial carcinoma or bladder cancer (based on previous imaging and /or histopathology)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Active malignancy other than urothelial carcinoma or bladder cancer
2. Administration of a radioisotope within 10 physical half-lives prior to study enrolment.
3. Administration of chemotherapy, radiotherapy, or immunotherapy within 4 weeks prior to planned administration of 89Zr-TLX250 or continuing adverse effects from such therapy
4. Planned antineoplastic therapies for the period between administration of 89Zr-TLX250 and imaging
5. Serious non-malignant disease that may interfere with the objectives of the study
6. Renal insufficiency with glomerular filtration rate less than or equal to 45 mL/min/1.73m2
7. Pregnancy or lactation
8. Exposure to murine or chimeric antibodies within the last 5 years
9. Known hypersensitivity or human anti-chimeric antibodies against girentuximab
10. Exposure to any experimental diagnostic or therapeutic drug 30 days prior to the date of planned administration of 89Zr-TLX250
11. Contraindications to FDG PET/CT

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)
Not applicable
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
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
A pragmatic target sample size of 20 patients has been chosen for this phase 1 feasibility study, based on clinical context and logistical factors. Descriptive statistics will be used in the reporting of the primary and secondary endpoints for this pilot study.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/05/2021
Actual
Date of last participant enrolment
Anticipated
15/12/2022
Actual
Date of last data collection
Anticipated
31/12/2022
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 18512 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 32851 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 307684 0
Commercial sector/Industry
Name [1] 307684 0
Telix International Pty Ltd
Country [1] 307684 0
Australia
Primary sponsor type
Government body
Name
South Metropolitan Health Services
Address
Level 2, Education Building, Fiona Stanley Hospital
14 Barry Marshall Parade, MURDOCH WA 6150
Country
Australia
Secondary sponsor category [1] 308395 0
None
Name [1] 308395 0
Address [1] 308395 0
Country [1] 308395 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307720 0
South Metropolitan Health Service Human Research Ethics Committee
Ethics committee address [1] 307720 0
Ethics committee country [1] 307720 0
Australia
Date submitted for ethics approval [1] 307720 0
29/10/2020
Approval date [1] 307720 0
10/11/2020
Ethics approval number [1] 307720 0

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

Contacts
Principal investigator
Name 108266 0
Prof Dickon Hayne
Address 108266 0
Perkins South, Fiona Stanley Hospital
102-118 Barry Marshall Parade
Murdoch WA 6150
Country 108266 0
Australia
Phone 108266 0
+61 8 6151 1130
Fax 108266 0
Email 108266 0
dickon.hayne@uwa.edu.au
Contact person for public queries
Name 108267 0
Jun Khai Wong
Address 108267 0
The University of Western Australia (M581), 35 Stirling Highway, 6009 Perth, Western Australia, Australia
Country 108267 0
Australia
Phone 108267 0
+61 861511106
Fax 108267 0
Email 108267 0
jun.khaiwong@uwa.edu.au
Contact person for scientific queries
Name 108268 0
Dickon Hayne
Address 108268 0
Perkins South, Fiona Stanley Hospital
102-118 Barry Marshall Parade
Murdoch WA 6150
Country 108268 0
Australia
Phone 108268 0
+61 8 6151 1130
Fax 108268 0
Email 108268 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?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
10378Informed consent form    381302-(Uploaded-28-01-2021-19-55-24)-Study-related document.doc
10379Study protocol    381302-(Uploaded-28-01-2021-19-56-36)-Study-related document.docx



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Embase89 Zirconium-labelled girentuximab (89 Zr-TLX250) PET in Urothelial Cancer Patients (ZiPUP): Protocol for a phase i trial of a novel staging modality for urothelial carcinoma.2022https://dx.doi.org/10.1136/bmjopen-2021-060478
N.B. These documents automatically identified may not have been verified by the study sponsor.