89Zr-TLX250 for PET/CT Imaging of ccRCC- ZIRCON Study (89ZR-TLX250)

A Confirmatory, Prospective, Open-label, Multi-centre Phase 3 Study to Evaluate Diagnostic Performance of Zirconium-labelled Girentuximab to Non-invasively Detect ccRCC by PET/CT Imaging in Patients With Indeterminate Renal Masses

89Zr-TLX250 is under clinical development as a diagnostic agent targeting clear cell renal cell carcinoma.

Study Overview

• Status: Completed
• Conditions: Clear Cell Renal Cell Carcinoma
• Intervention / Treatment: Diagnostic test: 89Zr-girentuximab

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.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
    • Sydney, New South Wales, Australia, 2109
      • Macquarie University Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health
    • Melbourne, Victoria, Australia, 3000
      • Victorian Comprehensive Cancer Centre
    • Melbourne, Victoria, Australia
      • Cabrini Hospital
• Belgium
  • Brussels, Belgium, 1000
    • Institute Jules Bordet
  • Leuven, Belgium, 3000
    • University Hospital Leuven (UZ Leuven)
• Canada
  • Québec, Canada, G1R2J6
    • CHU de Québec - Université Laval - L'Hôtel-Dieu de Québec
  • Quebec
    • Montréal, Quebec, Canada, H2X0C1
      • Centre De Recherche Centre hospitalier de l/Universite de Montreal (CrCHUM )
    • Montréal, Quebec, Canada, H3T 1E2
      • Jewish General Hopsital
• France
  • Bordeaux, France, 33076
    • CHU de Bordeaux, Groupe hospitalier Pellegrin
  • Nancy, France, 54500
    • Chru de Nancy, Hopitaux de Brabois
  • Nantes, France, 44000
    • Nantes University Hospital Hotel-Dieu
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Netherlands Cancer Institute
  • Nijmegen, Netherlands, 6500 HB
    • Radboud university medical centre
• Turkey
  • Ankara, Turkey, 06100
    • Ankara University Medical Faculty Hospital
  • Ankara, Turkey, 06230
    • Hacettepe University Faculty of Medicine
  • Istanbul, Turkey, 34098
    • Istanbul University Cerrahpasa Medical Faculty
  • Istanbul, Turkey, 34098
    • Istanbul Training and Research Hospital
• United Kingdom
  • London, United Kingdom, NW3 2QG
    • Royal Free London NHS Foundation Trust
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles Campus,
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University Hospital
    • Glen Burnie, Maryland, United States, 21061
      • Advanced Molecular Imaging & Therapy, LLC
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University St Louis
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance, University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

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
Experimental: 89Zr-girentuximab; A single administration of 37 Megabecquerel (MBq) (±10%) 89Zr-girentuximab, containing a mass dose of 10 mg of girentuximab, followed by a diagnostic scan on Day 5 ± 2 days after administration.	Diagnostic test: 89Zr-girentuximab; Single IV administration on Day 0, followed by diagnostic scan on Day 5 +/- 2 days.; Other Names: 89Zr-TLX250; 89Zr-DFO-TFP-girentuximab (GTX)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine sensitivity of 89Zr-TLX250 PET/CT imaging to detect ccRCC in the subgroup of patients with indeterminate renal masses of ≤ 4 cm in largest diameter (cT1a)	This outcome will be evaluated on all patients with a lesion ≤ 4cm in largest diameter by using a PET/CT machine to determine the uptake of the Zr89 radiotracer within the renal lesion. This amount of uptake in the lesion will be compared with the histologically determined cancer type following resection of the lesion	Single diagnostic administration, followed by a diagnostic scan on Day 5 ± 2 days. Resection to be conducted within 90 days of administration of 89Zr-girentuximab.
To determine specificity of 89Zr-TLX250 PET/CT imaging to detect ccRCC in the subgroup of patients with indeterminate renal masses of ≤ 4 cm in largest diameter (cT1a)	This outcome will be evaluated on all patients with a lesion ≤ 4cm in largest diameter by using a PET/CT machine to determine the uptake of the Zr89 radiotracer within the renal lesion. This amount of uptake in the lesion will be compared with the histologically determined cancer type following resection of the lesion	Single diagnostic administration, followed by a diagnostic scan on Day 5 ± 2 days. Resection to be conducted within 90 days of administration of 89Zr-girentuximab.
To evaluate positive predictive value (PPV), and accuracy of 89Zr-girentuximab PET/CT imaging to detect ccRCC in patients with indeterminate solid renal masses, and in patients with indeterminate renal masses of ≤ 4 cm (cT1a).	This outcome will be determining the proportion (as a percent) of the whole study population in which the PET/CT imaging could correctly predict if an individual patient had clear cell renal cell carcinoma or can correctly predict if the patient did not have clear cell renal cell carcinoma	This analysis will be conducted after all patients have completed study involvement
To define a standardized uptake value (SUV) cut-off for 89Zr-girentuximab, suitable to discriminate ccRCC from non-ccRCC	This outcome will be conducted on the whole study population and will use the counts derived from the PET/CT imaging of the 89Zr in the target tissue in order to see if there is a mathematical way to derive the tumour type information from the imaging alone. The tumour type will be determined by the histological sample obtained following resection.	Single diagnostic administration, followed by a diagnostic scan on Day 5 ± 2 days. Resection to be conducted within 90 days of administration of 89Zr-girentuximab
To evaluate the correlation between 89Zr- girentuximab SUVs and degree of histological carbonic anhydrase IX (CAIX) expression	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	Single diagnostic administration, followed by a diagnostic scan on Day 5 ± 2 days. Resection to be conducted within 90 days of administration of 89Zr-girentuximab
To evaluate inter-reader variability of diagnostic assessments of 89Zr- girentuximab PET/CT images, when performed by multiple readers	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.	This analysis will be conducted through study completion, on average of 5 months
To evaluate intra-reader variability of diagnostic assessments of 89Zr- girentuximab PET/CT images	This outcome will be conducted on a randomly determined subset of 10% of the patients. Three readers blinded to the histological outcome will be asked to read each patient PET/CT image on two occasions and determine if the target lesion is positive for Zr89. The results will be evaluated as a percent figure to consistently report the same finding with each patient.	This analysis will be conducted through study completion, on average of 5 months
To evaluate safety parameter of Heart rate in patients administered with 89Zr-girentuximab.	This outcome will be measured as beats per minute on all patients with treatment-related adverse events based on criteria as determined by the NCI CTCAE v 5.0 criteria	Patients will be evaluated for the 90 day period following administration of 89Zr-girentuximab
To evaluate safety parameter of blood pressure in patients administered with 89Zr-girentuximab.	This outcome will be measured as mmHg on all patients with treatment-related adverse events based on criteria as determined by the NCI CTCAE v 5.0 criteria	Patients will be evaluated for the 90 day period following administration of 89Zr-girentuximab
To evaluate negative predictive value (NPV) and accuracy of 89Zr-girentuximab PET/CT imaging to detect ccRCC in patients with indeterminate solid renal masses	This outcome will be determining the proportion (as a percent) of the whole study population in which the PET/CT imaging could correctly predict if an individual patient had clear cell renal cell carcinoma or can correctly predict if the patient did not have clear cell renal cell carcinoma	This analysis will be conducted through study completion, on average 5 months
To evaluate safety parameter related to Liver function in patients administered with 89Zr-girentuximab	This outcome will be measured on all patients with treatment-related adverse events based on criteria as determined by the NCI CTCAE v 5.0 criteria. Results will be assessed by number of participants with abnormal laboratory values.	Patients will be evaluated for the 90 day period following administration of 89Zr-girentuximab
To evaluate safety parameter related to Renal function in patients administered with 89Zr-girentuximab	This outcome will be measured on all patients with treatment-related adverse events based on criteria as determined by the NCI CTCAE v 5.0 criteria. Results will be assessed by number of participants with abnormal laboratory values.	Patients will be evaluated for the 90 day period following administration of 89Zr-girentuximab
To evaluate safety parameter related to Full Blood Count in patients administered with 89Zr-girentuximab	This outcome will be measured on all patients with treatment-related adverse events based on criteria as determined by the NCI CTCAE v 5.0 criteria. Results will be assessed by number of participants with abnormal laboratory values.	Patients will be evaluated for the 90 day period following administration of 89Zr-girentuximab
To evaluate sensitivity of 89Zr-TLX250 PET/CT imaging to detect ccRCC in patients with IRMs ≤ 3 cm lesions	This outcome will be evaluated on all patients with a lesion ≤ 3 cm in largest diameter by using a PET/CT machine to determine the uptake of the Zr89 radiotracer within the renal lesion. This amount of uptake in the lesion will be compared with the histologically determined cancer type following resection of the lesion.	Single diagnostic administration, followed by a diagnostic scan on Day 5 ± 2 days. Resection to be conducted within 90 days of administration of 89Zr-girentuximab.
To evaluate sensitivity of 89Zr-TLX250 PET/CT imaging to detect ccRCC in patients with IRMs ≤ 2 cm.	This outcome will be evaluated on all patients with a lesion ≤ 2 cm in largest diameter by using a PET/CT machine to determine the uptake of the Zr89 radiotracer within the renal lesion. This amount of uptake in the lesion will be compared with the histologically determined cancer type following resection of the lesion.	Single diagnostic administration, followed by a diagnostic scan on Day 5 ± 2 days. Resection to be conducted within 90 days of administration of 89Zr-girentuximab.
To evaluate sensitivity of 89Zr-TLX250 PET/CT imaging to detect ccRCC in patients with Bosniak 3 lesions.	This outcome will be evaluated on all patients with a Bosniak 3 lesion by using a PET/CT machine to determine the uptake of the Zr89 radiotracer within the renal lesion. This amount of uptake in the lesion will be compared with the histologically determined cancer type following resection of the lesion.	Single diagnostic administration, followed by a diagnostic scan on Day 5 ± 2 days. Resection to be conducted within 90 days of administration of 89Zr-girentuximab.
To evaluate sensitivity of 89Zr-TLX250 PET/CT imaging to detect ccRCC in patients with Bosniak 4 lesions.	This outcome will be evaluated on all patients with a Bosniak 4 lesion by using a PET/CT machine to determine the uptake of the Zr89 radiotracer within the renal lesion. This amount of uptake in the lesion will be compared with the histologically determined cancer type following resection of the lesion.	Single diagnostic administration, followed by a diagnostic scan on Day 5 ± 2 days. Resection to be conducted within 90 days of administration of 89Zr-girentuximab.
To evaluate specificity of 89Zr-TLX250 PET/CT imaging to detect ccRCC in patients with IRMs ≤ 3 cm lesions	This outcome will be evaluated on all patients with a lesion ≤ 3 cm in largest diameter by using a PET/CT machine to determine the uptake of the Zr89 radiotracer within the renal lesion. This amount of uptake in the lesion will be compared with the histologically determined cancer type following resection of the lesion.	Single diagnostic administration, followed by a diagnostic scan on Day 5 ± 2 days. Resection to be conducted within 90 days of administration of 89Zr-girentuximab.
To evaluate specificity of 89Zr-TLX250 PET/CT imaging to detect ccRCC in patients with IRMs ≤ 2 cm.	This outcome will be evaluated on all patients with a lesion ≤ 2 cm in largest diameter by using a PET/CT machine to determine the uptake of the Zr89 radiotracer within the renal lesion. This amount of uptake in the lesion will be compared with the histologically determined cancer type following resection of the lesion.	Single diagnostic administration, followed by a diagnostic scan on Day 5 ± 2 days. Resection to be conducted within 90 days of administration of 89Zr-girentuximab.
To evaluate specificity of 89Zr-TLX250 PET/CT imaging to detect ccRCC in patients with Bosniak 3 lesions.	This outcome will be evaluated on all patients with a Bosniak 3 by using a PET/CT machine to determine the uptake of the Zr89 radiotracer within the renal lesion. This amount of uptake in the lesion will be compared with the histologically determined cancer type following resection of the lesion.	Single diagnostic administration, followed by a diagnostic scan on Day 5 ± 2 days. Resection to be conducted within 90 days of administration of 89Zr-girentuximab.
To evaluate specificity of 89Zr-TLX250 PET/CT imaging to detect ccRCC in patients with Bosniak 4 lesions.	This outcome will be evaluated on all patients with a Bosniak 4 by using a PET/CT machine to determine the uptake of the Zr89 radiotracer within the renal lesion. This amount of uptake in the lesion will be compared with the histologically determined cancer type following resection of the lesion.	Single diagnostic administration, followed by a diagnostic scan on Day 5 ± 2 days. Resection to be conducted within 90 days of administration of 89Zr-girentuximab.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To quantitatively estimate achievable radiation absorbed doses (Gy) for therapeutic 177 Lutetium-girentuximab based on single time point 89Zr-girentuximab PET/CT images.	This outcome will be assessed by determining the radiation absorbed dose, using Monte Carlo analysis, that would have been delivered to the target tissue had the girentuximab been bound alternatively with the therapeutic radionuclide 177Lu, rather than the diagnostic 89Zr label.	This analysis will be conducted after all patients have completed study involvement, an average of 1 year
To quantitatively estimate achievable tumour uptake, retention and radiation absorbed doses (Gy) for therapeutic 177Lu-girentuximab, based on a general model of average girentuximab tumour kinetics derived from serial 89Zr-girentuximab imaging.	This outcome will be assessed by determining the radiation absorbed dose, using Monte Carlo analysis, that would have been delivered to the target tissue had the girentuximab been bound alternatively with the therapeutic radionuclide 177Lu, rather than the diagnostic 89Zr label.	This analysis will be conducted after all patients have completed study involvement, an average of 1 year
To quantitatively estimate achievable tumour uptake, retention and radiation absorbed doses (Gy) for therapeutic 177Lu-girentuximab, based on an assumed specific activity of 177Lu-girentuximab.	This outcome will be assessed by determining the radiation absorbed dose, using Monte Carlo analysis, that would have been delivered to the target tissue had the girentuximab been bound alternatively with the therapeutic radionuclide 177Lu, rather than the diagnostic 89Zr label.	This analysis will be conducted after all patients have completed study involvement, an average of 1 year
To evaluate the correlation between 89Zr-TLX250 SUVs and degree of histological CAIX expression.	This outcome will be conducted on the whole study population and will use the counts derived from the PET/CT imaging of the 89Zr in the target tissue and compare it to the CAIX expression determined by the histological sample obtained following resection.	Single diagnostic administration, followed by a diagnostic scan on Day 5 ± 2 days. Resection to be conducted within 90 days of administration of 89Zr-girentuximab
To evaluate distant masses outside the kidney identified on 89Zr-TLX250 whole body PET/CT in patients who present with unexpected evidence of disseminated disease.	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 there is evidence of disseminated disease with Zr89 which was not previously known.	This analysis will be conducted after all patients have completed study involvement

Collaborators and Investigators

• Sponsor: Telix Pharmaceuticals (Innovations) Pty Limited
• Investigators: Principal Investigator: Howard Gurney, MD, Macquarie University Hospital; Principal Investigator: Francoise Brodere, MD, University Hospital ICO, Nantes, France; Principal Investigator: Peter Mulders, MD, Radboud University Medical Center; Principal Investigator: Marcel Stokkel, MD, The Netherlands Cancer Institute; Principal Investigator: Declan Murphy, MD, Victorian Comprehensive Cancer Centre; Principal Investigator: Andrew Scott, MD, Olivia Newton John Cancer Research Center, Austin Hospital; Principal Investigator: Simon Wood, MD, Princess Alexander Hospital; Principal Investigator: Mark Frydenberg, MD, Cabrini Hospital; Principal Investigator: David Chan, Royal North Shore Hospital; Principal Investigator: Jean-Christophe Bernhard, MD, CHU de Bordeaux, Groupe hospitalier Pellegrin; Principal Investigator: Pierre Olivier, MD, CHRU de Nancy - Hôpitaux de Brabois; Principal Investigator: Linda Heijmen, MD, Leiden University Medical Centre; Principal Investigator: Martin Geert Steffens, MD, Isala; Principal Investigator: Karolien Goffin, MD, Universitair Ziekenhuis Leuven; Principal Investigator: Carlos Artigas Guix, MD, Instutit Jules Bordet; Principal Investigator: Nicolas Lumen, MD, Universitair Ziekenhuis Gent; Principal Investigator: Sumer Baltaci, MD, Ankara University; Principal Investigator: Bulent Akdogan, MD, Ankara Hacettepe University; Principal Investigator: Bulent Onal, MD, Istanbul University - Cerrahpasa (IUC); Principal Investigator: Tamer Aksoy, MD, Istanbul Training and Research Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2019
• Primary Completion (Actual): October 20, 2022
• Study Completion (Actual): November 7, 2022

Study Registration Dates

• First Submitted: January 29, 2019
• First Submitted That Met QC Criteria: February 19, 2019
• First Posted (Actual): February 21, 2019

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 9, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: clear cell renal cell carcinoma; PET/CT imaging; 89Zr-girentuximab
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell
• Other Study ID Numbers: 89Zr-TLX250-003

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