Assessment of safEty, Tolerability, Radiation Dosimetry, and Imaging Properties of 89Zr-labeled giRenTuximab (89Zr-Girentuximab) in patIents With Non-musclE-iNvasive Bladder CancEr (NMIBC)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the use of 89Zr-labeled girentuximab (89Zr-TLX250) as a novel, carbonic anhydrase IX (CAIX) targeted PET/CT radiopharmaceutical for the imaging of Non-muscle-invasive bladder cancer (NMIBC) patients.

Detailed Description
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There is a real need for treatment of NMIBC. Currently, treatment options include Bacillus Calmette-Guerin (BCG) intravesical immunotherapy and mitomycin C chemotherapy. These therapies are efficient for some time but relapses repeat them at more and more close intervals and finally patients are refractory to them and require a radical cystectomy. CAIX is expressed in 70% to 90% of bladder cancers but not in normal urothelial tissue. CAIX is expressed on the membrane of Non-Muscle-Invasive Bladder Cancer cells. Girentuximab, an anti-CAIX antibody could be a promising target in NMIBC. PET/CT with Girentuximab labelled with 89Zirconium will be used for diagnosis purpose. 89Zr-Girentuximab will be administered by intravesical instillation. In this study, patients with Non-Muscle-Invasive Bladder Cancer (NMIBC) will be enrolled in this study after confirmation of their eligibility. A single intravesical administration of 89Zr-Girentuximab will be performed at day 0. Multiple PET/CT imaging sessions will be performed on day 0, day 1 and day 2 in order to evaluate the bladder and the whole body 89Zr girentuximab uptake.

Official Title
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A Pilot Open-label, Feasibility Study to Assess safEty, Tolerability, Radiation Dosimetry, and Imaging Properties of 89Zr-labeled giRenTuximab (89Zr-Girentuximab) in patIents With Non-musclE-iNvasive Bladder CancEr (NMIBC)

Conditions
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Bladder Cancer

Intervention / Treatment
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* Drug: 89Zr-TLX250 PET/CT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. Female or male, Age ≥ 18 years at time of study entry. Performance Status: 0 or 1. Clinical evidence of NMIBC based on cystoscopy and proven histologically of papillary tumors. Histologically-confirmed pTa Grade 3 or pT1 Grade 3 bladder cancer patients relapsing without muscle invasion. Negative sterile Urine cytobacteriological testing at baseline (T0). Consent to use a contraception method for at least 30 days after administration of 89Zr-girentuximab. Patient has valid health insurance. Exclusion Criteria: Patient with urinary incontinence. Known hypersensitivity to girentuximab. Exposure to any experimental diagnostic or therapeutic drug within 30 days prior the date of planned administration of 89Zr-girentuximab Exposure to any radiopharmaceutical within 30 days (corresponding to 10 half-lives of Zr-89) prior to the administration of 89Zr-girentuximab Patients suffering from a bladder cancer at stage pT2, pT3 or pT4 Serious non-malignant disease that may interfere with the objectives of the study or with the safety or compliance of the patient; as judged by the investigator Concomitant cancer in the past 5 years except cutaneous cancers (except melanoma) and in situ carcinoma Prior chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy), immunotherapy within 21 days of 89Zr-girentuximab administration Patients with known human immunodeficiency viruses (HIV), Hepatitis B virus (HBV) and Hepatitis C Virus (HCV) infections, Pregnant or likely to be pregnant or nursing patient. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study Persons deprived of their liberty, under a measure of safeguard of justice, under guardianship or placed under the authority of a guardian.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Monocentric, open prospective study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 89Zr-TLX250 PET/CT<br>Pretherapeutic 89Zr-TLX250 PET/CT | Drug: 89Zr-TLX250 PET/CT<br>* Pretherapeutic 89Zr-TLX250 PET/CT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PET/CT imaging 89Zr-girentuximab biodistribution assessment | Standardized Uptake Values (SUVs) of bladder and whole body uptake will be evaluated by PET/CT imaging at T0, T0+2 hours, T0+20 hours and T0+44 hours | 3 days | 
| 89Zr-girentuximab Blood dosing | 89Zr-girentuximab activity dosing in blood will be measured (Becquerel/ml : Bq/ml) at T0+20 hours | 2 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the toxicity of 89Zr-girentuximab administered by intravesical instillation | Number of adverse events due to intravesical administration of 89Zr-Girentuximab up to Day 30 after 89Zr-girentuximab administration. Adverse events will be assessed by using CTC-AE scale version 5.0 | 30 days | 
| Radiation protection management | Radiation exposure of staff (extremities, lens and Whole body: µSv) | 3 days | 
| Radiation protection management | Radiopharmaceutical management from intravesical instillation to elimination (surfasic contamination: counts/cm2 or Bq/cm2) | 1 day | 
| Assess the degree of CAIX expression by immunohistochemistry of the tumor | The expression of CAIX will be assessed by immunohistochemistry in tumor sample from TransUrethral Resection of Bladder Tumor (TURBT) or cystectomy | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-muscle-invasive bladder cancer (NMIBC) patients, 89Zr-Girentuximab ((89Zirconium-Girentuximab) PET/CT, Safety assessment, pilot study, feasibility study, 89Zr-TLX250 (89Zirconium-TLX250) PET/CT, Positron Emission Tomography/Computerized Tomography (PET/CT) scan, carbonic anhydrase IX (CAIX)