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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03849118




Registration number
NCT03849118
Ethics application status
Date submitted
29/01/2019
Date registered
21/02/2019
Date last updated
20/08/2019

Titles & IDs
Public title
89Zr-TLX250 for PET/CT Imaging of ccRCC- ZIRCON Study
Scientific title
A Confirmatory, Prospective, Open-label, Multi-centre Phase 3 Study to Evaluate Diagnostic Performance of Zirconium-labelled Girentuximab to Non-invasively Detect ccRCC by PET/CT Imaging in Patients With Indeterminate Renal Masses
Secondary ID [1] 0 0
89Zr-TLX250-003
Universal Trial Number (UTN)
Trial acronym
89ZR-TLX250
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Clear Cell Renal Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Diagnosis / Prognosis - 89Zr-girentuximab

Experimental: 89Zr-girentuximab - A single administration of 37 Megabecquerel (MBq) (±10%) 89Zr-girentuximab, containing a mass dose of 10 mg of girentuximab, followed by a diagnostic scan on Day 5 ± 2 days after administration.


Diagnosis / Prognosis: 89Zr-girentuximab
Single IV administration on Day 0, followed by diagnostic scan on Day 5 +/- 2 days.

Intervention code [1] 0 0
Diagnosis / Prognosis
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To evaluate sensitivity and specificity of PET/CT imaging with 89Zr-TLX250 to non-invasively detect ccRCC in patients with indeterminate renal masses, using histology as standard of truth - This outcome will be evaluated on all patients by using a PET/CT machine to determine the uptake of the Zr89 radiotracer within the renal lesion. This will be compared against the histological determination of the lesion type following resection of the lesion
Timepoint [1] 0 0
Single diagnostic administration, followed by a diagnostic scan on Day 5 ± 2 days. Histological confirmation from nephrectomy material will serve as standard of truth.
Secondary outcome [1] 0 0
To evaluate sensitivity and specificity of 89Zr-girentuximab PET/CT imaging to detect ccRCC in the subgroup of patients with indeterminate renal masses of = 2cm in largest diameter using histology as standard of truth - This outcome will be evaluated on all patients with a lesion = 2cm in largest diameter by using a PET/CT machine to determine the uptake of the Zr89 radiotracer within the renal lesion. This amount of uptake in the lesion will be compared with the histologically determined cancer type following resection of the lesion
Timepoint [1] 0 0
Single diagnostic administration, followed by a diagnostic scan on Day 5 ± 2 days. Resection to be conducted within 90 days of administration of 89Zr-girentuximab.
Secondary outcome [2] 0 0
To evaluate positive predictive value (PPV), and accuracy of 89Zr-girentuximab PET/CT imaging to detect ccRCC in patients with indeterminate solid renal masses - This outcome will be determining the proportion (as a percent) of the whole study population in which the PET/CT imaging could correctly predict if an individual patient had clear cell renal cell carcinoma or can correctly predict if the patient did not have clear cell renal cell carcinoma
Timepoint [2] 0 0
This analysis will be conducted after all patients have completed study involvement
Secondary outcome [3] 0 0
To define a standardized uptake value (SUV) cut-off for 89Zr-girentuximab, suitable to discriminate ccRCC from non-ccRCC - This outcome will be conducted on the whole study population and will use the counts derived from the PET/CT imaging of the 89Zr in the target tissue in order to see if there is a mathematical way to derive the tumour type information from the imaging alone. The tumour type will be determined by the histological sample obtained following resection.
Timepoint [3] 0 0
Single diagnostic administration, followed by a diagnostic scan on Day 5 ± 2 days. Resection to be conducted within 90 days of administration of 89Zr-girentuximab
Secondary outcome [4] 0 0
To evaluate the correlation between 89Zr- girentuximab SUVs and degree of histological carbonic anhydrase IX (CAIX) expression - This outcome will be assessed on all patients. The counts derived from the PET/CT imaging of the renal lesion will be compared with the amount of CAIX expressed in the histologically extracted sample
Timepoint [4] 0 0
Single diagnostic administration, followed by a diagnostic scan on Day 5 ± 2 days. Resection to be conducted within 90 days of administration of 89Zr-girentuximab
Secondary outcome [5] 0 0
To evaluate inter-reader variability of diagnostic assessments of 89Zr- girentuximab PET/CT images, when performed by multiple readers - This outcome will be conducted on all patients. Three blinded readers operating independently will be used to read each patient PET/CT image and determine if the target lesion is positive for Zr89. A comparison of findings will then be made between the readers for each patient individually.
Timepoint [5] 0 0
This analysis will be conducted through study completion, on average of 5 months
Secondary outcome [6] 0 0
To evaluate intra-reader variability of diagnostic assessments of 89Zr- girentuximab PET/CT images - This outcome will be conducted on a randomly determined subset of 10% of the patients. Three readers blinded to the histological outcome will be asked to read each patient PET/CT image on two occasions and determine if the target lesion is positive for Zr89. The results will be evaluated as a percent figure to consistently report the same finding with each patient.
Timepoint [6] 0 0
This analysis will be conducted through study completion, on average of 5 months
Secondary outcome [7] 0 0
To evaluate safety parameter of Heart rate in patients administered with 89Zr-girentuximab. - This outcome will be measured as beats per minute on all patients with treatment-related adverse events based on criteria as determined by the NCI CTCAE v 5.0 criteria
Timepoint [7] 0 0
Patients will be evaluated for the 90 day period following administration of 89Zr-girentuximab
Secondary outcome [8] 0 0
To evaluate safety parameter of blood pressure in patients administered with 89Zr-girentuximab. - This outcome will be measured as mmHg on all patients with treatment-related adverse events based on criteria as determined by the NCI CTCAE v 5.0 criteria
Timepoint [8] 0 0
Patients will be evaluated for the 90 day period following administration of 89Zr-girentuximab
Secondary outcome [9] 0 0
To evaluate negative predictive value (NPV) and accuracy of 89Zr-girentuximab PET/CT imaging to detect ccRCC in patients with indeterminate solid renal masses - This outcome will be determining the proportion (as a percent) of the whole study population in which the PET/CT imaging could correctly predict if an individual patient had clear cell renal cell carcinoma or can correctly predict if the patient did not have clear cell renal cell carcinoma
Timepoint [9] 0 0
This analysis will be conducted through study completion, on average 5 months
Secondary outcome [10] 0 0
To evaluate safety parameter related to Liver function in patients administered 89Zr-girentuximab - This outcome will be measured on all patients with treatment-related adverse events based on criteria as determined by the NCI CTCAE v 5.0 criteria. Results will be assessed by number of participants with abnormal laboratory values.
Timepoint [10] 0 0
Patients will be evaluated for the 90 day period following administration of 89Zr-girentuximab
Secondary outcome [11] 0 0
To evaluate safety parameter related to Renal function in patients administered 89Zr-girentuximab - This outcome will be measured on all patients with treatment-related adverse events based on criteria as determined by the NCI CTCAE v 5.0 criteria. Results will be assessed by number of participants with abnormal laboratory values.
Timepoint [11] 0 0
Patients will be evaluated for the 90 day period following administration of 89Zr-girentuximab
Secondary outcome [12] 0 0
To evaluate safety parameter related to Full Blood Count in patients administered 89Zr-girentuximab - This outcome will be measured on all patients with treatment-related adverse events based on criteria as determined by the NCI CTCAE v 5.0 criteria. Results will be assessed by number of participants with abnormal laboratory values.
Timepoint [12] 0 0
Patients will be evaluated for the 90 day period following administration of 89Zr-girentuximab

Eligibility
Key inclusion criteria
1. Written and voluntarily given Informed Consent

2. Male or female =18 years of age

3. Imaging evidence of a single indeterminate renal mass of =7cm in largest diameter
(tumour stage cT1) , on CT or MRI with and without contrast agent, suspicious for
ccRCC

4. Scheduled for lesion resection as part of regular diagnostic work-up within 90 days
from planned 89Zr-TLX250 administration

5. Negative serum pregnancy tests in female patients of childbearing potential (at
Screening and within 24 hours prior to receiving investigational product)

6. for patients included in France only, verification and confirmation of their
affiliation with a social security

7. Sufficient life expectancy to justify nephrectomy

8. Consent to practice double-barrier contraception until a minimum of 42 days after
89Zr-TLX250 administration
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Bioptic procedure (rather than a partial or total nephrectomy) planned for
histological species delineation of IRM

2. Renal mass known to be a metastasis of another primary tumour

3. Active non-renal malignancy requiring therapy during the time frame of the study
participation

4. Chemotherapy, radiotherapy or immunotherapy within 4 weeks prior to the planned
administration of 89Zr-TLX250 or continuing adverse effects (> grade 1) from such
therapy (Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)

5. Planned antineoplastic therapies (for the period between administration of 89
Zr-TLX250 and imaging)

6. Exposure to murine or chimeric antibodies within the last 5 years

7. Previous administration of any radionuclide within 10 half-lives of the same

8. Serious non-malignant disease (e.g. psychiatric, infectious, autoimmune or metabolic)
that may interfere with the objectives of the study or within the safety of compliance
of the subjects as judged by the Investigator

9. Mental impairment that may compromise the ability to give Informed Consent and comply
with the requirements of the study

10. Exposure to any experimental diagnostic or therapeutic drug within 30 days from the
date of planned administration of 89Zr-TLX250

11. Women who are pregnant or breastfeeding

12. Known hypersensitivity to Girentuximab or DFO (Desferrioxamine)

13. Renal insufficiency with glomerular filtration rate (GFR) = 60 millilitres/min/1.73m2

14. Vulnerable patients (e.g being in detention)

Study design
Purpose of the study
Diagnosis
Allocation to intervention
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 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 0 0
Macquarie University Hospital - Sydney
Recruitment hospital [3] 0 0
Austin Health - Heidelberg
Recruitment hospital [4] 0 0
Victorian Comprehensive Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
2109 - Sydney
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Netherlands
State/province [1] 0 0
Amsterdam
Country [2] 0 0
Netherlands
State/province [2] 0 0
Nijmegen
Country [3] 0 0
Turkey
State/province [3] 0 0
Ankara
Country [4] 0 0
Turkey
State/province [4] 0 0
Istanbul

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Telix International Pty Ltd
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
89Zr-TLX250 is under clinical development as a diagnostic agent targeting clear cell renal
cell carcinoma.
Trial website
https://clinicaltrials.gov/show/NCT03849118
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Howard Gurney, MD
Address 0 0
Macquarie University Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Telix Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
+61 3 9093 3808
Fax 0 0
Email 0 0
global-clinicaltrials@telixpharma.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03849118