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

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)

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.

Study Overview

• Status: Completed
• Conditions: Urothelial Carcinoma
• Intervention / Treatment: Drug: 89Zr-Girentuximab

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 Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Administration of 89Zr-Girentuximab; Administration of 89Zr-Girentuximab as per protocol	Drug: 89Zr-Girentuximab; Administration of 89Zr-girentuximab as per protocol.

What is the study measuring?

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
Number of participants with treatment related adverse events 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 quantify 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

Collaborators and Investigators

• Sponsor: South Metropolitan Health Service
• Collaborators: Telix Pharmaceuticals (Innovations) Pty Limited

Publications and helpful links

General Publications

• Al-Zubaidi M, Viswambaram P, McCombie S, Liow E, Lenzo N, Ferguson T, Redfern AD, Gauci R, Hayne D. 89Zirconium-labelled girentuximab (89Zr-TLX250) PET in Urothelial Cancer Patients (ZiPUP): protocol for a phase I trial of a novel staging modality for urothelial carcinoma. BMJ Open. 2022 Apr 15;12(4):e060478. doi: 10.1136/bmjopen-2021-060478.

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2021
• Primary Completion (Actual): August 9, 2022
• Study Completion (Actual): August 9, 2022

Study Registration Dates

• First Submitted: September 8, 2021
• First Submitted That Met QC Criteria: September 8, 2021
• First Posted (Actual): September 16, 2021

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Glandular and Epithelial
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Carcinoma, Transitional Cell
• Other Study ID Numbers: ZiPUP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No