ZIRDAC-JP: Evaluation of Safety, Biodistibution and Sensitivity/Specificity of PET/CT Imaging With 89Zr-TLX250 in Subjects With RCC
Study Details
Study Description
Brief Summary
89Zr-TLX250 is a carbonic anydrase IX (CAIX)-targeted imaging agent that is under clinical development as a non-invasive diagnostic imaging agent for teh detection of clear cell renal cell carcinoma (ccRCC). The Phase 1 study part of this study is to confirm the safety/tolerability and to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) in subjects with suspected renal cell carcinoma (RCC) including clear cell renal cell carcinoma. The Phase 2 component of the study is to to evaluate the sensitivity/specificity of using 89Zr-TLX250 PET/CT images to detect RCC and ccRCC in patients with suspected RCC.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
Phase 1:
The phase 1 component of this study will be conducted in in 6-10 subjects at one study center, with the objective of confirming the safety/tolerability and the whole-body dose distribution of 89Zr-TLX250. 89Zr-TLX250 will be administered via a single IV injection (at least 3 min) at an activity dose of 37 MBq (± 10%) and at a dose of 10 mg (±10%). After the enrollment of 6 subjects, if the male-to-female ratio is different from the Japanese epidemiological RCC data (male-to-female ratio ≒ 2:1 in 2017), more subjects, up to 10 subjects in total, are to be enrolled.
Blood sampling for pharmacokinetic analysis will be is performed at 0.5, 1, 2, 4, 24, 72 h and during the Day 5 ± 2 imaging visit. The dose distribution will be determined using low-dose, non-contrast-enhanced CT whole body imaging at 0.5, 4, 24, 72 h and Day 5 ± 2. Diagnostic images will be acquired on Day 3 and Day 5 ± 2 using whole body PET/CT-imaging where individual organs will be assessed using Medical Internal Radiation Dose (MIRD) method.
Seven days after the Day 5 ± 2 imaging visit, patients will attend a follow-up visit to conduct safety evaluations and to undergo blood sampling for HACA measurement.
Phase 2:
The phase 2 component of this study will be conducted after the completion of the phase 1 study in 6-10 patients. This part of the study is equivalent to a phase 2, open-label, multi-center (2-5 sites) to assess the sensitivity/specificity of PET/CT images in subjects with suspected but not definitely diagnosed RCC including ccRCC. The study is intended to evaluate the sensitivity and specificity of PET/CT test as a non-invasive test with the CAIX-targeted imaging agent 89Zr-TLX250. The study will include patients who are scheduled to undergo a partial or total nephrectomy. Patients with an indeterminate renal mass with the longest diameter of 7cm or less, by diagnostic imaging, will receive a single administration of 37 MBq (+/- 10%) 89Zr-TLX250. Imaging will then be conducted Day 5 ± 2 post administration. The partial/total nephrectomy will 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.
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 89Zr-girentuximab A single administration of 37 Megabecquerel (MBq) (±10%) 89Zr-girentuximab, containing a mass dose of 10 mg of girentuximab |
Diagnostic Test: 89Zr-girentuximab
A single dose of 37 MBq (±10%) is administered. The dose per dose is equivalent to girentuximab 10 mg (±10%).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Incidence of Treatment-Emergent Adverse events [Safety and Tolerability] [90 days]
Incidence of abnormal laboratory test results and abnormal vital signs
- Determination of the sensitivity and specificity of 89Zr-TLX250 to detect clear cell renal cell carcinoma [90 days]
The sensitivity and specificity of 89Zr-TLX250 to detect renal cell carcinoma will be established by a diagnostic scan after administration of the investigational product followed by surgery of the indeterminate mass. After surgical removal of the kidney mass , diagnostic histology of the mass will be conducted and used as the "standard of truth" comparator.
Secondary Outcome Measures
- Phase 1: Evaluation of the radioactivity distribution and biodistribution/tumor uptake [0.5, 4, 24, and 72 hours and Day 5 ± 2]
Whole body PET/CT imaging (from the base of skull to the thigh) performed post-injection using non-contrast-enhanced and low-dose CT for absorption correction.
- Phase 1: Assessment of tumor uptake [Day 3-5]
This outcome will be evaluated by determining the absorbed dose after injection with 89Zr-TLX250 in identifiable tumor regions taking into account the tumor volume estimated from imaging performed prior to participation to the study.
- Phase 2: To evaluate positive predictive value (PPV) of 89Zr-girentuximab PET/CT imaging to detect ccRCC in patients with indeterminate solid renal masses [At end of study , on average of 5 months]
Positive predictive value (PPV) in detecting ccRCC by PT/CT imaging using 89Zr-TLX250 in subjects with undiagnosed solid renal mass
- Phase 2: To evaluate negative predictive value (NPV) of 89Zr-girentuximab PET/CT imaging to detect ccRCC in patients with indeterminate solid renal masses [At end of study , on average of 5 months]
Negative predictive value (NPV) using 89Zr-TLX250 in subjects with undiagnosed solid renal mass
- To evaluate accuracy of 89Zr-girentuximab PET/CT imaging to detect ccRCC in patients with indeterminate solid renal masses [At end of study , on average of 5 months]
Determine accuracy in detecting ccRCC by PT/CT imaging using 89Zr-TLX250 in subjects with undiagnosed solid renal mass
- Phase 2: To evaluate the correlation between 89Zr- girentuximab SUVs and degree of histological carbonic anhydrase IX (CAIX) expression [Within 90 days]
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
- Phase 2: To evaluate inter-reader variability of diagnostic assessments of 89Zr- girentuximab PET/CT images, when performed by multiple readers [This analysis will be conducted through study completion, on average of 5 months]
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.
- Phase 2: Assessment of differences in a same reader [This analysis will be conducted through study completion, on average of 5 months]
The difference in evaluations of 89Zr-TLX250 PET/CT images by a same reader is assessed with the use of Cohen's κ coefficient.
Eligibility Criteria
Criteria
Inclusion Criteria:
Phase 1:
-
Written and voluntarily given informed consent
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Aged ≥20 years at the time of enrollment
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Suspected renal cell carcinoma who have been diagnosed with a renal mass by CT or MRI performed within 90 days before screening
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Sufficient life expectancy to participate in the study
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Consent to practice barrier contraception (condoms) until a minimum of 42 days and 90 days after 89Zr-TLX250 administration in female and male, respectively
Phase 2 Part
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Written and voluntarily given informed consent
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Aged ≥20 years at the time of enrollment
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Imaging evidence of a single indeterminate renal mass of ≤ 7 cm in largest diameter on CT or MRI within 90 days prior to screening
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Scheduled for lesion resection as part of regular diagnostic work-up within 90 days from planned 89Zr-TLX250 administration
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Sufficient life expectancy to undergo nephrectomy
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Consent to practice barrier contraception (condoms) until a minimum of 42 days and 90 days after 89Zr-TLX250 administration in female and male, respectively
Exclusion Criteria:
Commonly applied for Phase 1 part and Phase 2 part
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Those who have hypersensitivity to Girentuximab or DFO
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Patients with metastatic renal tumor
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Patients who need treatment for other active malignancies during the study period
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Patients who have undergone chemotherapy, radiation therapy, or immunotherapy within 4 weeks before the administration of the investigational drug, or have continued adverse events of grade 1 (defined in NCI-CTCAE v5.0) or higher
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Patients scheduled for anticancer drug treatment during the period from administration of investigational drug to image collection
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Patients who have been exposed to mouse or chimeric antibody within the past 5 years
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Patients who have been administered some kind of radionuclide earlier than 10 half-lives of the nuclide.
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Patients with severe, but not fatal disease, for which the principal investigator / investigator has determined that study participation is not appropriate
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Women who are pregnant or breastfeeding. And women with childbearing potential who are not pregnant or breastfeeding but suspected of being pregnant by the blood test at screening and pre-dose (within 24 hours before administration). Pre-dose blood pregnancy test can be replaced with urine test
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Patients who have been administered the drug by any clinical study or clinical trial within 30 days before the scheduled administration of the investigational drug
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Patients who cannot give legally valid consent by himself / herself
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Patients with renal dysfunction whose GFR is 60mL / min / 1.73m2 or less
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Patents who are socially vulnerable (e.g., patients in custody)
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Others who are judged by the principal investigator or investigator to be inappropriate for participation in this trial Applied only to Phase 2 part 15． Patients whose biopsy is more suitable for pathological diagnosis than partial resection or nephrectomy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Yokohama City University Hospital | Yokohama City | Kanagawa | Japan | 236-0004 |
Sponsors and Collaborators
- Telix International Pty Ltd
Investigators
- Principal Investigator: Noboru Nakaigawa, MD, PhD, Yokohama City University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 89Zr-TLX250-004