Clear Cell Renal Cell Carcinoma
Conditions
Keywords
clear cell renal cell carcinoma, PET/CT imaging, 89Zr-girentuximab
Brief summary
89Zr-TLX250 is under clinical development as a diagnostic agent targeting clear cell renal cell carcinoma.
Detailed description
This is a confirmatory, prospective, open-label, multi-centre phase 3 study to evaluate sensitivity and specificity of 89Zr-TLX250 Positron Emission Tomography/Computed Tomography (PET/CT) imaging to non-invasively detect clear cell renal cell cancer (ccRCC) in adult patients with indeterminate renal masses (IRM), scheduled for partial or total nephrectomy. Patients, will be recruited in 12-15 renal cancer care specialist centres, who have access to state-of-the-art PET/CT imaging equipment. The study involves a single administration of 89Zr-TLX250. Imaging will then be conducted 5 +/-2 days post administration. The partial/total nephrectomy will then be performed at institutional discretion any time following the PET/CT imaging visit, but no later than 90 days post administration of 89Zr-TLX250. Histological tumour samples will be prepared and used for histological diagnosis of the renal mass (ccRCC or non-ccRCC) read by a central laboratory. On Day 5 +/-2 post study drug administration, an abdominal PET/CT imaging will be obtained. In patients, in which unexpected evidence for disseminated disease is observed, PET/CT imaging may be extended to complete whole body imaging(vertex of skull to toe) at the discretion of the investigator. Image data analyses will be performed by a central image core lab. Qualitative visual analysis (presence or absence of localised 89Zr-TLX250 uptake inside or in vicinity of renal lesion, as seen on contrast-enhanced CT or MRI), will be used to assess test performance or 89Zr-TLX-250 PET/CT imaging to non-invasively detect ccRCC, using histological results from the central histological reference laboratory as standard of truth.
Interventions
DIAGNOSTIC_TEST89Zr-girentuximab
Single IV administration on Day 0, followed by diagnostic scan on Day 5 +/- 2 days.
Sponsors
Telix Pharmaceuticals (Innovations) Pty Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
diagnostic, confirmatory, prospective, multi-centre
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity and Specificity of Qualitative Assessment of PET/CT Imaging With 89Zr-TLX250 to Noninvasively Detect ccRCC in Patients With Indeterminate Renal Masses, Using Histology as Standard of Truth. | Diagnostic PET/CT scan on Day 5 ± 2 days post 89Zr-TLX250 administration. Histological confirmation of the material from nephrectomy conducted within 90 days post 89Zr-TLX250 administration served as standard of truth. | This outcome was evaluated on all patients by using a PET/CT machine to determine the uptake of the Zr89 radiotracer within the renal lesion. This was compared against the histological determination of the lesion type following resection of the lesion |
Countries
Australia, Belgium, Canada, France, Netherlands, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 89Zr-girentuximab A single administration of 37 MBq (±10%) 89Zr-TLX250, containing a mass dose of 10 mg of girentuximab followed by a diagnostic scan on Day 5 ± 2 days | 300 |
| Total | 300 |
Baseline characteristics
| Characteristic | 89Zr-girentuximab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 124 Participants |
| Age, Categorical Between 18 and 65 years | 176 Participants |
| Age, Continuous | 62 years STANDARD_DEVIATION 11.8 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 participants |
| Race/Ethnicity, Customized Asian | 9 participants |
| Race/Ethnicity, Customized Black or African American | 13 participants |
| Race/Ethnicity, Customized Missing | 1 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants |
| Race/Ethnicity, Customized White | 277 participants |
| Region of Enrollment Australia | 35 participants |
| Region of Enrollment Belgium | 29 participants |
| Region of Enrollment Canada | 6 participants |
| Region of Enrollment France | 45 participants |
| Region of Enrollment Netherlands | 38 participants |
| Region of Enrollment Spain | 4 participants |
| Region of Enrollment Turkey | 29 participants |
| Region of Enrollment United Kingdom | 1 participants |
| Region of Enrollment United States | 113 participants |
| Sex: Female, Male Female | 86 Participants |
| Sex: Female, Male Male | 214 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 300 |
| other Total, other adverse events | 86 / 300 |
| serious Total, serious adverse events | 26 / 300 |
Outcome results
Primary
Sensitivity and Specificity of Qualitative Assessment of PET/CT Imaging With 89Zr-TLX250 to Noninvasively Detect ccRCC in Patients With Indeterminate Renal Masses, Using Histology as Standard of Truth.
This outcome was evaluated on all patients by using a PET/CT machine to determine the uptake of the Zr89 radiotracer within the renal lesion. This was compared against the histological determination of the lesion type following resection of the lesion
Time frame: Diagnostic PET/CT scan on Day 5 ± 2 days post 89Zr-TLX250 administration. Histological confirmation of the material from nephrectomy conducted within 90 days post 89Zr-TLX250 administration served as standard of truth.
Population: The overall number of participants analyzed consisted of all enrolled patients who had evaluable PET/CT imaging and a confirmed histopathology diagnosis. This number (284) is lower than the baseline participants (of 300) as 16 patients did not have both of these data points.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 89Zr-girentuximab | Sensitivity and Specificity of Qualitative Assessment of PET/CT Imaging With 89Zr-TLX250 to Noninvasively Detect ccRCC in Patients With Indeterminate Renal Masses, Using Histology as Standard of Truth. | True negative | 84 Participants |
| 89Zr-girentuximab | Sensitivity and Specificity of Qualitative Assessment of PET/CT Imaging With 89Zr-TLX250 to Noninvasively Detect ccRCC in Patients With Indeterminate Renal Masses, Using Histology as Standard of Truth. | False positive | 11 Participants |
| 89Zr-girentuximab | Sensitivity and Specificity of Qualitative Assessment of PET/CT Imaging With 89Zr-TLX250 to Noninvasively Detect ccRCC in Patients With Indeterminate Renal Masses, Using Histology as Standard of Truth. | False negative | 30 Participants |
| 89Zr-girentuximab | Sensitivity and Specificity of Qualitative Assessment of PET/CT Imaging With 89Zr-TLX250 to Noninvasively Detect ccRCC in Patients With Indeterminate Renal Masses, Using Histology as Standard of Truth. | True Positive | 159 Participants |