PHASE III ZIRCON STUDY

Detection of renal masses is increasing due to widespread use of cross-sectional imaging but current imaging is unable to reliably distinguish benign or malignant lesions from ccRCC.

To evaluate sensitivity and specificity of PET/CT imaging with TLX250-CDx 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.

For more information on the ZIRCON study see: https://clinicaltrials.gov/ct2/show/NCT03849118 

Secondary Outcome Measures:

1. To determine sensitivity and specificity of ⁸⁹Zr-TLX250 PET/CT imaging to detect ccRCC in the subgroup of patients with indeterminate renal masses of ≤ 4 cm in largest diameter (cT1a)
2. To determine positive predictive value (PPV), negative predictive value (NPV), and accuracy of ⁸⁹Zr-TLX250 PET/CT imaging to detect ccRCC in patients with indeterminate solid renal masses, and in the subgroup of patients with indeterminate renal masses of ≤ 4 cm (cT1a)
3. To identify a standardized uptake value (SUV) cut-off for ⁸⁹Zr-TLX250, suitable to discriminate ccRCC from non-ccRCC
4. To determine inter-reader variability of diagnostic assessments of ⁸⁹Zr-TLX250 PET/CT images, when performed by multiple readers
5. To determine intra-reader variability of diagnostic assessment of ⁸⁹Zr-TLX250 PET/CT images
6. To establish safety and tolerability of ⁸⁹Zr-TLX250 in patients with indeterminate renal masses.

For more information on the ZIRCON study see: https://clinicaltrials.gov/ct2/show/NCT03849118

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.

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).