Clinical trial NCT03849118: 89Zr-TLX250 for PET/CT Imaging of ccRCC- ZIRCON Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Clear Cell Renal Cell Carcinoma
Keywords: clear cell renal cell carcinoma
PET/CT imaging
89Zr-girentuximab
Lead sponsor: Telix Pharmaceuticals (Innovations) Pty Limited
Sponsor class: INDUSTRY
First posted: 2019-02-21
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: diagnostic, confirmatory, prospective, multi-centre
Primary purpose: DIAGNOSTIC

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

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.

Eligibility criteria: 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)

Primary outcomes:
measure: 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.
timeFrame: 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 outcomes:
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles Campus,
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins University Hospital
state: Maryland
city: Glen Burnie
country: United States
facility: Advanced Molecular Imaging & Therapy, LLC
state: Maryland
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Washington University St Louis
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Seattle
country: United States
facility: SEATTLE CANCER CARE ALLIANCE, University of Washington
state: Washington
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Macquarie University Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Victorian Comprehensive Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: Cabrini Hospital
state: Victoria
city: Brussels
country: Belgium
facility: Institute Jules Bordet
city: Leuven
country: Belgium
facility: University Hospital Leuven (UZ Leuven)
city: Montréal
country: Canada
facility: Centre De Recherche Centre hospitalier de l/Universite de Montreal (CrCHUM )
state: Quebec
city: Montréal
country: Canada
facility: Jewish General Hopsital
state: Quebec
city: Québec
country: Canada
facility: CHU de Québec - Université Laval - L'Hôtel-Dieu de Québec
city: Bordeaux
country: France
facility: CHU de Bordeaux, Groupe hospitalier Pellegrin
city: Nancy
country: France
facility: CHRU de Nancy, Hopitaux de Brabois
city: Nantes
country: France
facility: Nantes University Hospital Hotel-Dieu
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Centre
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty Hospital
city: Ankara
country: Turkey
facility: Hacettepe University Faculty of Medicine
city: Istanbul
country: Turkey
facility: Istanbul Training and Research Hospital
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Medical Faculty
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
Study officials:
affiliation: Macquarie University Hospital
name: Howard Gurney, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital ICO, Nantes, France
name: Francoise Brodere, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radboud University Medical Center
name: Peter Mulders, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Netherlands Cancer Institute
name: Marcel Stokkel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Victorian Comprehensive Cancer Centre
name: Declan Murphy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Olivia Newton John Cancer Research Center, Austin Hospital
name: Andrew Scott, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Princess Alexander Hospital
name: Simon Wood, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cabrini Hospital
name: Mark Frydenberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal North Shore Hospital
name: David Chan
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU de Bordeaux, Groupe Hospitalier Pellegrin
name: Jean-Christophe Bernhard, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHRU de Nancy - Hôpitaux de Brabois
name: Pierre Olivier, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Leiden University Medical Centre
name: Linda Heijmen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Isala
name: Martin Geert Steffens, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitair Ziekenhuis Leuven
name: Karolien Goffin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instutit Jules Bordet
name: Carlos Artigas Guix, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitair Ziekenhuis Gent
name: Nicolas Lumen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ankara University
name: Sumer Baltaci, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ankara Hacettepe University
name: Bulent Akdogan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Istanbul University - Cerrahpasa
name: Bulent Onal, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Istanbul Training and Research Hospital
name: Tamer Aksoy, MD
role: PRINCIPAL_INVESTIGATOR
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