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

• ClinicalTrials.gov Identifier: NCT03849118
• Recruitment Status: Completed
• First Posted: February 21, 2019
• Last Update Posted: April 14, 2023
• Sponsor: Telix International Pty Ltd
• Information provided by (Responsible Party): Telix International Pty Ltd

Study Description

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 300 participants
• Allocation: N/A
• 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: August 15, 2019
• Actual Primary Completion Date: October 20, 2022
• Actual Study Completion Date: November 7, 2022

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. To evaluate 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. [ 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 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) [ 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 ≤ 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
2. 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) [ 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 ≤ 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
3. 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). [ 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
4. 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.
5. 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
6. 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.
7. 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.
8. 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
9. 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
10. 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
11. To evaluate safety parameter related to Liver function 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 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 Renal function 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 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.
13. To evaluate safety parameter related to Full Blood Count 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 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.
14. To evaluate sensitivity of 89Zr-TLX250 PET/CT imaging to detect ccRCC in patients with IRMs ≤ 3 cm lesions [ 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 ≤ 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.
15. To evaluate sensitivity of 89Zr-TLX250 PET/CT imaging to detect ccRCC in patients with IRMs ≤ 2 cm. [ 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 ≤ 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.
16. To evaluate sensitivity of 89Zr-TLX250 PET/CT imaging to detect ccRCC in patients with Bosniak 3 lesions. [ 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 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.
17. To evaluate sensitivity of 89Zr-TLX250 PET/CT imaging to detect ccRCC in patients with Bosniak 4 lesions. [ 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 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.
18. To evaluate specificity of 89Zr-TLX250 PET/CT imaging to detect ccRCC in patients with IRMs ≤ 3 cm lesions [ 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 ≤ 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.
19. To evaluate specificity of 89Zr-TLX250 PET/CT imaging to detect ccRCC in patients with IRMs ≤ 2 cm. [ 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 ≤ 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.
20. To evaluate specificity of 89Zr-TLX250 PET/CT imaging to detect ccRCC in patients with Bosniak 3 lesions. [ 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 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.
21. To evaluate specificity of 89Zr-TLX250 PET/CT imaging to detect ccRCC in patients with Bosniak 4 lesions. [ 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 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.

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.
2. 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. [ 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.
3. 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. [ 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.
4. To evaluate the correlation between 89Zr-TLX250 SUVs and degree of histological 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 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.
5. 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. [ Time Frame: This analysis will be conducted after all patients have completed study involvement ]
   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.

Eligibility Criteria

• 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)

Contacts and Locations

Locations

United States, California

City of Hope Comprehensive Cancer Center

Duarte, California, United States, 91010

University of California, Los Angeles Campus,

Los Angeles, California, United States, 90095

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

United States, Maryland

Johns Hopkins University Hospital

Baltimore, Maryland, United States, 21287

Advanced Molecular Imaging & Therapy, LLC

Glen Burnie, Maryland, United States, 21061

United States, Michigan

Barbara Ann Karmanos Cancer Hospital

Detroit, Michigan, United States, 48201

United States, Missouri

Washington University St Louis

Saint Louis, Missouri, United States, 63110

United States, New York

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

United States, Washington

SEATTLE CANCER CARE ALLIANCE, University of Washington

Seattle, Washington, United States, 98109

Australia, New South Wales

Royal North Shore Hospital

St Leonards, New South Wales, Australia, 2065

Macquarie University Hospital

Sydney, New South Wales, Australia, 2109

Australia, Queensland

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia, 4029

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia, 4102

Australia, Victoria

Austin Health

Heidelberg, Victoria, Australia, 3084

Victorian Comprehensive Cancer Centre

Melbourne, Victoria, Australia, 3000

Cabrini Hospital

Melbourne, Victoria, Australia

Belgium

Institute Jules Bordet

Brussels, Belgium, 1000

University Hospital Leuven (UZ Leuven)

Leuven, Belgium, 3000

Canada, Quebec

Centre De Recherche Centre hospitalier de l/Universite de Montreal (CrCHUM )

Montréal, Quebec, Canada, H2X0C1

Jewish General Hopsital

Montréal, Quebec, Canada, H3T 1E2

Canada

CHU de Québec - Université Laval - L'Hôtel-Dieu de Québec

Québec, Canada, G1R2J6

France

CHU de Bordeaux, Groupe hospitalier Pellegrin

Bordeaux, France, 33076

CHRU de Nancy, Hopitaux de Brabois

Nancy, France, 54500

Nantes University Hospital Hotel-Dieu

Nantes, France, 44000

Netherlands

Netherlands Cancer Institute

Amsterdam, Netherlands, 1066 CX

Radboud University Medical Centre

Nijmegen, Netherlands, 6500 HB

Turkey

Ankara University Medical Faculty Hospital

Ankara, Turkey, 06100

Hacettepe University Faculty of Medicine

Ankara, Turkey, 06230

Istanbul Training and Research Hospital

Istanbul, Turkey, 34098

Istanbul University Cerrahpasa Medical Faculty

Istanbul, Turkey, 34098

United Kingdom

Royal Free London NHS Foundation Trust

London, United Kingdom, NW3 2QG

Sponsors and Collaborators

Telix International Pty Ltd

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

More Information

• Responsible Party: Telix International Pty Ltd
• ClinicalTrials.gov Identifier: NCT03849118
• Other Study ID Numbers: 89Zr-TLX250-003
• First Posted: February 21, 2019
• Last Update Posted: April 14, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• 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:

Carcinoma, Renal Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases