MedPath

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

Early Phase 1
Completed
Conditions
Bladder Cancer
Interventions
Drug: 89Zr-TLX250 PET/CT
Registration Number
NCT04897763
Lead Sponsor
Institut Cancerologie de l'Ouest
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
6
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
89Zr-TLX250 PET/CT89Zr-TLX250 PET/CTPretherapeutic 89Zr-TLX250 PET/CT
Primary Outcome Measures
NameTimeMethod
PET/CT imaging 89Zr-girentuximab biodistribution assessment3 days

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

89Zr-girentuximab Blood dosing2 days

89Zr-girentuximab activity dosing in blood will be measured (Becquerel/ml : Bq/ml) at T0+20 hours

Secondary Outcome Measures
NameTimeMethod
Radiation protection management1 day

Radiopharmaceutical management from intravesical instillation to elimination (surfasic contamination: counts/cm2 or Bq/cm2)

Assess the toxicity of 89Zr-girentuximab administered by intravesical instillation30 days

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

Assess the degree of CAIX expression by immunohistochemistry of the tumor3 months

The expression of CAIX will be assessed by immunohistochemistry in tumor sample from TransUrethral Resection of Bladder Tumor (TURBT) or cystectomy

Trial Locations

Locations (1)

Institut de cancerologie de l'Ouest

🇫🇷

Saint Herblain, France

© Copyright 2025. All Rights Reserved by MedPath