Assessment of safEty, Tolerability, Radiation Dosimetry, and Imaging Properties of 89Zr-labeled giRenTuximab (89Zr-Girentuximab) in patIents With Non-musclE-iNvasive Bladder CancEr (NMIBC) (PERTINENCE)
Primary Purpose
Bladder Cancer
Status
Completed
Phase
Early Phase 1
Locations
France
Study Type
Interventional
Intervention
89Zr-TLX250 PET/CT
Sponsored by
About this trial
This is an interventional diagnostic trial for Bladder Cancer focused on measuring 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)
Eligibility Criteria
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.
Sites / Locations
- Institut de cancerologie de l'Ouest
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
89Zr-TLX250 PET/CT
Arm Description
Pretherapeutic 89Zr-TLX250 PET/CT
Outcomes
Primary Outcome Measures
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
89Zr-girentuximab Blood dosing
89Zr-girentuximab activity dosing in blood will be measured (Becquerel/ml : Bq/ml) at T0+20 hours
Secondary Outcome Measures
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
Radiation protection management
Radiation exposure of staff (extremities, lens and Whole body: µSv)
Radiation protection management
Radiopharmaceutical management from intravesical instillation to elimination (surfasic contamination: counts/cm2 or Bq/cm2)
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
Full Information
NCT ID
NCT04897763
First Posted
May 17, 2021
Last Updated
February 20, 2023
Sponsor
Institut Cancerologie de l'Ouest
Collaborators
ATONCO
1. Study Identification
Unique Protocol Identification Number
NCT04897763
Brief Title
Assessment of safEty, Tolerability, Radiation Dosimetry, and Imaging Properties of 89Zr-labeled giRenTuximab (89Zr-Girentuximab) in patIents With Non-musclE-iNvasive Bladder CancEr (NMIBC)
Acronym
PERTINENCE
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
October 1, 2021 (Actual)
Primary Completion Date
August 24, 2022 (Actual)
Study Completion Date
September 26, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut Cancerologie de l'Ouest
Collaborators
ATONCO
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer
Keywords
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)
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Monocentric, open prospective study
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
89Zr-TLX250 PET/CT
Arm Type
Experimental
Arm Description
Pretherapeutic 89Zr-TLX250 PET/CT
Intervention Type
Drug
Intervention Name(s)
89Zr-TLX250 PET/CT
Intervention Description
Pretherapeutic 89Zr-TLX250 PET/CT
Primary Outcome Measure Information:
Title
PET/CT imaging 89Zr-girentuximab biodistribution assessment
Description
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
Time Frame
3 days
Title
89Zr-girentuximab Blood dosing
Description
89Zr-girentuximab activity dosing in blood will be measured (Becquerel/ml : Bq/ml) at T0+20 hours
Time Frame
2 days
Secondary Outcome Measure Information:
Title
Assess the toxicity of 89Zr-girentuximab administered by intravesical instillation
Description
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
Time Frame
30 days
Title
Radiation protection management
Description
Radiation exposure of staff (extremities, lens and Whole body: µSv)
Time Frame
3 days
Title
Radiation protection management
Description
Radiopharmaceutical management from intravesical instillation to elimination (surfasic contamination: counts/cm2 or Bq/cm2)
Time Frame
1 day
Title
Assess the degree of CAIX expression by immunohistochemistry of the tumor
Description
The expression of CAIX will be assessed by immunohistochemistry in tumor sample from TransUrethral Resection of Bladder Tumor (TURBT) or cystectomy
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Caroline ROUSSEAU, MD, PhD
Organizational Affiliation
Institut de Cancerologie de l'Ousest - ICO
Official's Role
Study Chair
Facility Information:
Facility Name
Institut de cancerologie de l'Ouest
City
Saint Herblain
ZIP/Postal Code
44805
Country
France
12. IPD Sharing Statement
Learn more about this trial
Assessment of safEty, Tolerability, Radiation Dosimetry, and Imaging Properties of 89Zr-labeled giRenTuximab (89Zr-Girentuximab) in patIents With Non-musclE-iNvasive Bladder CancEr (NMIBC)
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