Phase I Study to Evaluate the Diagnostic Performance of 89Zirconium Girentuximab PET in Urothelial Cancer Patients

Phase 1

Completed

• Conditions: Urothelial Carcinoma
• Interventions: Drug: 89Zr-Girentuximab

• Registration Number: NCT05046665
• Lead Sponsor: South Metropolitan Health Service

Brief Summary

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

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.

Study Timeline

• Study Start: 2021-05-14
• Study First Submitted: 2021-09-08
• Study First Submitted QC: 2021-09-08
• Study First Posted: 2021-09-16
• Primary Completion: 2022-08-09
• Study Completion: 2022-08-09
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-18
• Last Update Posted: 2024-04-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

Inclusion Criteria

1. Patients aged 18 or older with bladder cancer or urothelial carcinoma who are able to provide informed consent
2. 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.
3. Consent to practise double-barrier contraception until a minimum of 42 days after 89Zr-TLX250 administration.

Exclusion Criteria

1. Active malignancy other than urothelial carcinoma or bladder cancer
2. Administration of a radioisotope within 10 physical half-lives prior to study enrolment.
3. Administration of chemotherapy, radiotherapy, or immunotherapy within 4 weeks prior to planned administration of 89Zr-TLX250 or continuing adverse effects from such therapy
4. Planned antineoplastic therapies for the period between administration of 89Zr-TLX250 and imaging
5. Serious non-malignant disease that may interfere with the objectives of the study
6. Renal insufficiency with glomerular filtration rate ≤45 mL/min/1.73m2
7. Pregnancy or lactation
8. Exposure to murine or chimeric antibodies within the last 5 years
9. Known hypersensitivity or human anti-chimeric antibodies against girentuximab
10. Exposure to any experimental diagnostic or therapeutic drug 30 days prior to the date of planned administration of 89Zr-TLX250
11. Contraindications to FDG PET/CT

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Administration of 89Zr-Girentuximab	89Zr-Girentuximab	Administration of 89Zr-Girentuximab as per protocol

Primary Outcome Measures

Name	Time	Method
Comparison of the sensitivity and specificity of 89Zr-girentuximab PET with FDG PET	Day 1 - Day 90	Sensitivity and specificity will be established following histological confirmation

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Fiona Stanley Hospital; 🇦🇺 Murdoch, Western Australia, Australia