E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with an indeterminate renal mass (IRM) detected on contrast-enhanced abdominal MR imaging or equivalent standard of care imaging, clinically suspicious for renal cell carcinoma and scheduled for lesion resection as part of the regular diagnostic work-up/clinical care. |
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E.1.1.1 | Medical condition in easily understood language |
Patients with an indeterminate renal mass (IRM) detected during imaging, clinically suspicious for renal cell carcinoma and scheduled for lesion resection |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. 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.
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E.2.2 | Secondary objectives of the trial |
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 ≤ 2 cm in largest diameter 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 3. To identify a standardized uptake value (SUV) cut-off for 89Zr TLX250, suitable to discriminate ccRCC from non-ccRCC 4. To evaluate the correlation between 89Zr-TLX250 SUVs and degree of histological CAIX expression 5. To determine inter-reader variability of diagnostic assessments of 89Zr-TLX250 PET/CT images, when performed by multiple readers 6. To determine intra-reader variability of diagnostic assessment of 89Zr-TLX250 PET/CT images 7. To establish safety and tolerability of 89Zr-TLX250 in patients with indeterminate renal masses.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Included in the given study protocol (for the sub-study no separate objectives) 89Zr-TLX250 PET/CT imaging Abdominal PET/CT scans including the kidneys will be acquired over 20 minutes in a single bed position if possible at a single time point on Day 5 ± 2 post administration (p.a.) of 89Zr-TLX250 using static image acquisition and low dose CT. Patients found to have evidence of N1 or M1 disease may undergo additional whole body PET/CT imaging (skull base to mid-thigh) as part of a sub-study using 6-8 bed positions with 10 minutes acquisition time per bed position at the discretion of the treating clinician in the intent to support comprehensive staging. The additional scan if requested by the treating physician needs to be completed within 7 days of the administration of the investigational product. The additional images collected will be included as a sub-study analysis for the purpose of the study. In cases, where staging results in a cancellation of the planned nephrectomy, patients need to be replaced.
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E.3 | Principal inclusion criteria |
All patients must meet all of the following 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 ≤ 7 cm in largest diameter (tumour stage cT1), on MRI or equivalent standard of care imaging, with contrast agent, not older than 90 days on Day 0, but performed before any screening procedure, 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 confirmation of negative pregnancy test result from urine 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 practise double-barrier contraception until a minimum of 42 days after 89Zr-TLX250 administration.
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E.4 | Principal exclusion criteria |
A patient will be excluded from participation in the trial if one or more of the following criteria are met: 1. A bioptic procedure only (rather than 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 89Zr-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 with the safety or compliance of the subject, 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 (desferoxamine) 13. Renal insufficiency with GFR ≤ 60 mL/min/ 1.73 m² 14. Vulnerable patients (e.g. being in detention)
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary study objective is to evaluate the diagnostic efficacy of 89Zr-TLX250 as a non-invasive diagnostic tool for the detection of clear cell renal carcinoma. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Treatment: IMP administered on Day 0 Imaging visit: Day 5 ± 2 days (whole body PET/CT imaging) |
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E.5.2 | Secondary end point(s) |
Test performance parameters (sensitivity, specificity, positive and negative predictive values, accuracy), will be determined considering visually determined qualitatitive 89Zr-TLX250 tumour uptake (yes/no), and histology (ccRCC+/ ccRCC-) as standard of truth. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Treatment: IMP administered on Day 0 Imaging visit: Day 5 ± 2 days (whole body PET/CT imaging) Surgery visit: any time after imaging visit, but no later than Day 90 p.a. (Surgical resection material will be sent to local pathology for routine histological work-up (H&E staining, histological diagnosis: ccRCC vs. non-ccRCC). Central pathology service, for independent confirmation of histological diagnosis. In addition, CAIX expression.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Canada |
France |
Netherlands |
Spain |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |