Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03849118
Recruitment Status : Recruiting
First Posted : February 21, 2019
Last Update Posted : August 20, 2019
Sponsor:
Information provided by (Responsible Party):
Telix International Pty Ltd

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

Condition or disease Intervention/treatment Phase
Clear Cell Renal Cell Carcinoma Diagnostic Test: 89Zr-girentuximab Phase 3

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 252 participants
Intervention Model: Single Group Assignment
Intervention Model Description: diagnostic, confirmatory, prospective, multi-centre
Masking: None (Open Label)
Primary Purpose: Diagnostic
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
Actual Study Start Date : April 15, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : June 30, 2021


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)




Primary Outcome Measures :
  1. To evaluate sensitivity and specificity of PET/CT imaging with 89Zr-TLX250 to non-invasively detect ccRCC in patients with indeterminate renal masses, using histology as standard of truth [ Time Frame: Single diagnostic administration, followed by a diagnostic scan on Day 5 ± 2 days. Histological confirmation from nephrectomy material will serve as standard of truth. ]
    This outcome will be evaluated on all patients by using a PET/CT machine to determine the uptake of the Zr89 radiotracer within the renal lesion. This will be compared against the histological determination of the lesion type following resection of the lesion


Secondary Outcome Measures :
  1. To evaluate sensitivity and specificity of 89Zr-girentuximab PET/CT imaging to detect ccRCC in the subgroup of patients with indeterminate renal masses of ≤ 2cm in largest diameter using histology as standard of truth [ Time Frame: 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. ]
    This outcome will be evaluated on all patients with a lesion ≤ 2cm 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

  2. To evaluate positive predictive value (PPV), and accuracy of 89Zr-girentuximab PET/CT imaging to detect ccRCC in patients with indeterminate solid renal masses [ Time Frame: This analysis will be conducted after all patients have completed study involvement ]
    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

  3. To define a standardized uptake value (SUV) cut-off for 89Zr-girentuximab, suitable to discriminate ccRCC from non-ccRCC [ Time Frame: 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 ]
    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.

  4. To evaluate the correlation between 89Zr- girentuximab SUVs and degree of histological carbonic anhydrase IX (CAIX) expression [ Time Frame: 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 ]
    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

  5. To evaluate inter-reader variability of diagnostic assessments of 89Zr- girentuximab PET/CT images, when performed by multiple readers [ Time Frame: This analysis will be conducted through study completion, on average of 5 months ]
    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.

  6. To evaluate intra-reader variability of diagnostic assessments of 89Zr- girentuximab PET/CT images [ Time Frame: This analysis will be conducted through study completion, on average of 5 months ]
    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.

  7. To evaluate safety parameter of Heart rate in patients administered with 89Zr-girentuximab. [ Time Frame: Patients will be evaluated for the 90 day period following administration of 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

  8. To evaluate safety parameter of blood pressure in patients administered with 89Zr-girentuximab. [ Time Frame: Patients will be evaluated for the 90 day period following administration of 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

  9. To evaluate negative predictive value (NPV) and accuracy of 89Zr-girentuximab PET/CT imaging to detect ccRCC in patients with indeterminate solid renal masses [ Time Frame: This analysis will be conducted through study completion, on average 5 months ]
    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

  10. To evaluate safety parameter related to Liver function in patients administered 89Zr-girentuximab [ Time Frame: Patients will be evaluated for the 90 day period following administration of 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.

  11. To evaluate safety parameter related to Renal function in patients administered 89Zr-girentuximab [ Time Frame: Patients will be evaluated for the 90 day period following administration of 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.

  12. To evaluate safety parameter related to Full Blood Count in patients administered 89Zr-girentuximab [ Time Frame: Patients will be evaluated for the 90 day period following administration of 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.


Other Outcome Measures:
  1. To quantitatively estimate achievable radiation absorbed doses (Gy) for therapeutic 177 Lutetium-girentuximab based on single time point 89Zr-girentuximab PET/CT images [ Time Frame: This analysis will be conducted after all patients have completed study involvement, an average of 1 year ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03849118


Contacts
Layout table for location contacts
Contact: Telix Pharmaceuticals +61 3 9093 3808 global-clinicaltrials@telixpharma.com

Locations
Layout table for location information
Australia, New South Wales
Royal North Shore Hospital Recruiting
St Leonards, New South Wales, Australia, 2065
Contact: Paul Roach, MD         
Contact: Dale Bailey, MD         
Macquarie University Hospital Recruiting
Sydney, New South Wales, Australia, 2109
Contact: Howard Gurney, MD         
Principal Investigator: Howard Gurney, MD         
Australia, Victoria
Austin Health Recruiting
Heidelberg, Victoria, Australia, 3084
Contact: Andrew Scott, MD         
Contact: Sze Ting Lee, MD         
Victorian Comprehensive Cancer Centre Recruiting
Melbourne, Victoria, Australia, 3000
Contact: Declan Murphy, MD         
Contact: Amir Irivani, MD         
Netherlands
Netherlands Cancer Institute Recruiting
Amsterdam, Netherlands, 1066 CX
Contact: Marcel Stokkel, MD         
Radboud University Medical Centre Recruiting
Nijmegen, Netherlands, 6500 HB
Contact: Peter Mulder, MD         
Turkey
Ankara University Medical Faculty Hospital Recruiting
Ankara, Turkey, 06100
Contact: Sumer Baltaci, MD         
Hacettepe University Faculty of Medicine Recruiting
Ankara, Turkey, 06230
Contact: Bulent Akdogan, MD         
Istanbul Training and Research Hospital Recruiting
Istanbul, Turkey, 34098
Contact: Tamer Aksoy, MD         
Istanbul University Cerrahpasa Medical Faculty Recruiting
Istanbul, Turkey, 34098
Contact: Bulent Onal, MD         
Sponsors and Collaborators
Telix International Pty Ltd
Investigators
Layout table for investigator information
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
Principal Investigator: Marcel Stokkel, MD The Netherlands Cancer Institute
Principal Investigator: Declan Murphy, MD Victorian Comprehensive Cancer Centre

Layout table for additonal information
Responsible Party: Telix International Pty Ltd
ClinicalTrials.gov Identifier: NCT03849118     History of Changes
Other Study ID Numbers: 89Zr-TLX250-003
First Posted: February 21, 2019    Key Record Dates
Last Update Posted: August 20, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Telix International Pty Ltd:
clear cell renal cell carcinoma
PET/CT imaging
89Zr-girentuximab
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma, Renal Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs