Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000824561
Ethics application status
Approved
Date submitted
19/06/2024
Date registered
4/07/2024
Date last updated
29/09/2024
Date data sharing statement initially provided
4/07/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Clearview-BC: A phase 1 Positron Emission Tomography (PET) - Computed Tomography (CT) study to evaluate the safety, biodistribution and pharmacokinetics of 89Zr-hu/mo-10D7 in patients with Bladder Cancer
Scientific title
Clearview-BC: A phase 1 PET-CT study to evaluate the safety, biodistribution and pharmacokinetics of 89Zr-hu/mo-10D7 in patients with Bladder Cancer
Secondary ID [1] 312364 0
nil
Universal Trial Number (UTN)
Trial acronym
Clearview-BC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Bladder Cancer 334149 0
Condition category
Condition code
Cancer 330821 330821 0 0
Bladder

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will receive a single intravenous dose of 89Zr-hu/mo-10D7 (up to 4.5 mg protein; 37 MBq radiation) as an intravenous infusion over 30 minutes under a low-risk, micro-dosing regimen. Administration of 89Zr-hu/mo-10D7 will be undertaken by Registered Nurses within the Dept of Nuclear Medicine, RBWH.
Imaging PET-CT scans will be undertaken by a Nuclear Medicine Technologist at the Herston Imaging Research Facility (HIRF) at the following timepoints:
Day 0 - 4 hours post infusion
Day 1 - approx 24 hours post infusion
Day 3* - 3 days post infusion (+/- 1 day)
Day 7 - 7 days post infusion (+/- 1 day)
Duration of the imaging is approximately 15-30mins. No further injections will occur post administration of the investigative agent.
Intervention code [1] 328861 0
Diagnosis / Prognosis
Comparator / control treatment
There is no control group, however, comparison is with prior diagnostic CT scan and uptake on an FDG-PET scan.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 338587 0
Determine the safety of 89Zr-hu/mo-10D7 in patients who have advanced metastatic bladder cancer.
Safety will be assessed by the incidence of Adverse Events including but not limited to vital signs such as heart rate, blood pressure, respiratory rate and temperature.
Timepoint [1] 338587 0
Screening visit
Baseline (Pre-dose)
30 mins post administration
1 hour post administration
2 hours post administration
4 hours post administration
Day 2 (24 hours) post administration
Day 3 (+/- 1 day) post administration
Day 7 (+/- 1 day) post administration
Primary outcome [2] 338588 0
Safety will be determined by Electrocardiogram (ECG) to review significant changes from baseline and post administration
Timepoint [2] 338588 0
Screening
2 hours post administration.
Primary outcome [3] 338589 0
Safety will be determined by biochemistry, coagulation and haematology data to review significant changes from baseline and post administration
Timepoint [3] 338589 0
Screening
Day 0 Baseline
Day 3 (+/- 1 day) post administration
Day 7 (+/- 1 day) post administration
Secondary outcome [1] 436505 0
Future theranostic use.

This will be assessed as a composite outcome.
Timepoint [1] 436505 0
PET-CT scans will be undertaken on Day 0 at 4 hours, and Day 1, Day 3*, and Day 7* after injection of the tracer (*+/- 1 day).
Secondary outcome [2] 436506 0
Determine the pharmacokinetics of hu/mo-10D7

This will be assessed as a composite outcome
Timepoint [2] 436506 0
PET/CT scans will be performed after administration of 89Zr-hu/mo-10D7 at the following timepoints:
Day 0 - 4 hours post infusion
Day 1 - approx 24 hours post infusion
Day 3 - 3 days post infusion (+/- 1 day)
Day 7 - 7 days post infusion (+/- 1 day)

PK sampling - PK blood samples are to be taken from a peripheral vein of the arm opposite the infusion site for the determination of activity at the following time points after administration of 89Zr-hu/mo-10D7 on day 0 at 1 hour, 2 hours, 4 hours, Day 1 (24 hours), day 3* and day 7* (*+/- 1 day).
Aliquots of blood and, plasma, and will be measured for 89Zr radioactivity in an isotope well-counter, compared with an aliquot retained from the conjugate preparation, and corrected for decay. Blood activity to be expressed as the percentage of the injected dose per kilogram.
Secondary outcome [3] 436507 0
Perform dosimetry estimates for both malignant bladder tumour and normal human tissues to determine if there is a suitable therapeutic window.

This will be assessed as a composite outcome
Timepoint [3] 436507 0
PET/CT scans will be performed after administration of 89Zr-hu/mo-10D7 at the following timepoints:
Day 0 - 4 hours post infusion
Day 1 - approx 24 hours post infusion
Day 3* - 3 days post infusion (+/- 1 day)
Day 7 - 7 days post infusion (+/- 1 day)

Eligibility
Key inclusion criteria
• Provide a signed and dated informed consent form
• Be willing to comply with all study procedures and be available for the duration of the study
• Adults greater than or equal to 18 years
• Have histologically proven invasive bladder cancer
• Visible metastatic disease on diagnostic CT and/or FDG-PET imaging
• CDCP1 expression proven on tumour sample
• ECOG 0-1
• Expected survival more than 3 months
• Women of reproductive potential must use highly effective contraception and abstain from getting period during the trial period
• Adequate organ function. Out of range values that are not clinically significant will be permitted, except for the following laboratory parameters, which must be within the ranges specified:
Serum AST and ALT less than or equal to 2.5 x ULN
Serum bilirubin less than or equal to 1.5 x ULN
eGFR GFR greater than or equal to 30 mL/min/ 1.73 m²
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• History of major immunologic reaction to any IgG containing agent
• Prior or ongoing clinically significant illness, medical condition(s), surgical history, physical finding, electrocardiogram (ECG) finding, or laboratory abnormality that, in the investigator’s opinion, could places the subject at an unacceptably high risk, adversely affect the safety of the subject or impair the assessment of study results
• Subject is pregnant, lactating, or and/or plans to become pregnant within the trial period
• Exposure within the past 5 years to chimeric or murine antibodies
• Exposure to a radiopharmaceuticals within the washout period (washout 10 half-lives of the radionuclide)
• Concurrent participation in another clinical trial

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
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
SAMPLE SIZE:
The sample size of up to 20 patients was selected based on previous disease-stratifying 89Zr-labelled antibody studies in:
- breast cancer (n=23, anti-VEGFA antibody
- colorectal cancer (n=7; anti-EGFR antibody
- head and neck cancer (n=20; anti-CD44v6 antibody
- pancreatic and ovarian cancer (n=11; anti-mesothelin antibody

DATA ANALYSIS
1. The suitability of hu/mo-10D7 for subsequent use as a theranostic will be assessed for PET scans by measurement of uptake in tumours compared with uptake in normal tissues, using both semi-quantitative measures (SUVmax ratios) as well as formal organ and tumour dosimetry estimates from multi time point imaging.

2. 89Zr-hu/mo-10D7 parameters will also be determined from whole blood concentration-time data measured by scintillation counting and mass spectrometry are: Maximum Observed Plasma Concentration (Cmax); Terminal Phase Half-life (t1/2); Mean Residence Time (MRT); Elimination Rate Constant (Lambda-z); and Clearance rate. Mean Tumour and Organ Dose and Effective Dose of 89Zr-hu/mo-10D7 in tumours and organs, as a fraction of total MBq dose will be determined from PET-CT scans for all participants.

3. Safety will be assessed based on collated data for the cohort of:
i) Adverse events (AE) and serious adverse events (SAE) relating to liver, kidney, cardio-vascular, immunological and haematological toxicities including:
ii) Clinical Chemistry Data - glucose, creatinine, phosphorous, magnesium, calcium, carbon dioxide content, albumin, potassium and sodium.
ii) Haematology Data - haemoglobin, lymphocytes, haematocrit, neutrophil count, platelet count and white blood cell count.
iv) ECG- to review significant changes from baseline to post administration.
v) Vital signs (including pulse rate, blood pressure, temperature, respiratory rate).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/11/2024
Actual
Date of last participant enrolment
Anticipated
1/09/2026
Actual
Date of last data collection
Anticipated
1/10/2026
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 26708 0
Mater Hospital Brisbane - South Brisbane
Recruitment hospital [2] 26709 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 42747 0
4101 - South Brisbane
Recruitment postcode(s) [2] 42748 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 316772 0
Government body
Name [1] 316772 0
Australian Federal Government CUREator Funding scheme
Country [1] 316772 0
Australia
Primary sponsor type
University
Name
University of Queensland
Address
Country
Australia
Secondary sponsor category [1] 318988 0
None
Name [1] 318988 0
Address [1] 318988 0
Country [1] 318988 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315540 0
Metro North Health Human Research Ethics Committee A
Ethics committee address [1] 315540 0
Ethics committee country [1] 315540 0
Australia
Date submitted for ethics approval [1] 315540 0
28/06/2024
Approval date [1] 315540 0
19/09/2024
Ethics approval number [1] 315540 0

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

Contacts
Principal investigator
Name 135018 0
A/Prof Paul Thomas
Address 135018 0
Department of Nuclear Medicine, Royal Brisbane & Women's Hospital, Butterfield Street, Herston QLD 4029
Country 135018 0
Australia
Phone 135018 0
+61 736467593
Fax 135018 0
Email 135018 0
[email protected]
Contact person for public queries
Name 135019 0
Professor John Hooper
Address 135019 0
Mater Research Institute - The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba QLD 4102
Country 135019 0
Australia
Phone 135019 0
+61 734437639
Fax 135019 0
Email 135019 0
[email protected]
Contact person for scientific queries
Name 135020 0
Professor John Hooper
Address 135020 0
Mater Research Institute - The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba QLD 4102
Country 135020 0
Australia
Phone 135020 0
+61 734437639
Fax 135020 0
Email 135020 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


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.