A Single-centre, Open-label, Phase I Study to Evaluate the Diagnostic Performance of 89Zirconium-labelled Girentuximab (89Zr-TLX250) PET in Urothelial Cancer Patients (ZiPUP Study)

Study Overview
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Brief Summary
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The aim of this study is to determine if it is practical to use 89Zr-TLX250 PET/CT in the staging and detection of localized and metastatic urothelial carcinoma or bladder cancer. The primary objective is to evaluate the feasibility of using 89Zr-TLX250 PET/CTas a new diagnostic and staging modality to detect urothelial carcinoma or bladder cancer.

Detailed Description
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This will be a non-randomised, non-blinded, single centre, phase 1 feasibility study comparing 89Zr-girentuximab PET with FDG PET in patients with urothelial carcinoma or bladder cancer. This study would include 2 cohorts of adult patients; those with known metastatic urothelial carcinoma and bladder cancer and those undergoing primary staging for recently diagnosed urothelial carcinoma or bladder cancer. This study is open-label, single centre and eligible patients will receive a single administration of study drug prior to imaging on day 5 (+/- 2 days). PET scans will be independently interpreted by nuclear medicine physicians blinded to the FDG PET findings. For patients proceeding to radical cystectomy, subsequent histological confirmation of areas of increased uptake will be retrospectively correlated with both PET scans.

Official Title
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A Single-centre, Open-label, Phase I Study to Evaluate the Diagnostic Performance of 89Zirconium-labelled Girentuximab (89Zr-TLX250) PET in Urothelial Cancer Patients (ZiPUP Study)

Conditions
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Urothelial Carcinoma

Intervention / Treatment
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* Drug: 89Zr-Girentuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18 or older with bladder cancer or urothelial carcinoma who are able to provide informed consent Negative serum pregnancy test in female patients of childbearing potential at screening. Confirmation of negative pregnancy test result from urine within 24 hours prior to receiving investigational product. Consent to practise double-barrier contraception until a minimum of 42 days after 89Zr-TLX250 administration. Exclusion Criteria: Active malignancy other than urothelial carcinoma or bladder cancer Administration of a radioisotope within 10 physical half-lives prior to study enrolment. Administration of chemotherapy, radiotherapy, or immunotherapy within 4 weeks prior to planned administration of 89Zr-TLX250 or continuing adverse effects from such therapy Planned antineoplastic therapies for the period between administration of 89Zr-TLX250 and imaging Serious non-malignant disease that may interfere with the objectives of the study Renal insufficiency with glomerular filtration rate ≤45 mL/min/1.73m2 Pregnancy or lactation Exposure to murine or chimeric antibodies within the last 5 years Known hypersensitivity or human anti-chimeric antibodies against girentuximab Exposure to any experimental diagnostic or therapeutic drug 30 days prior to the date of planned administration of 89Zr-TLX250 Contraindications to FDG PET/CT

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Staging cohort<br>Eligible participants recruited to the staging cohort | Drug: 89Zr-Girentuximab<br>* Administration of 89Zr-girentuximab as per protocol.<br>|
| Other: Metastatic cohort<br>Eligible participants recruited from the metastatic cohort | Drug: 89Zr-Girentuximab<br>* Administration of 89Zr-girentuximab as per protocol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the sensitivity and specificity of 89Zr-girentuximab PET with FDG PET | Sensitivity and specificity will be established following histological confirmation | Day 1 - Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the correlation between 89Zr-girentuximab SUV's and degree of urinary carbonic anhydrase IX excretion (cytology and CA-IX via PCR). | 89Zr-girentuximab SUV's will be correlated with urinary CA-IX expression | Day 1 | 
| To evaluate safety parameters related to 89Zr-girentuximab administration | Number of participants with treatment-related adverse events as assessed by NCI-CTCAE v 5.0 criteria | Day 1 to Day 90 | 
| To evaluate the correlation between tumour volume using MIM quantitative software and histopathological findings | Tumour burden as defined by volumetric software will be correlated with histopathological results | Day 1 - Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glandular and Epithelial