Bladder Cancer
Conditions
Keywords
Non-muscle-invasive bladder cancer (NMIBC), 89Zr-Girentuximab PET, pilot study, 89Zr-TLX250 PET, carbonic anhydrase IX (CAIX)
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.
Interventions
DRUG89Zr-TLX250
89Zr-TLX250 (89Zr-girentuximab) PET/CT performed for all aptients
Sponsors
ATONCO
Institut Cancerologie de l'Ouest
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Monocentric, open prospective study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Uptake Spot in 89Zr-girentuximab PET/CT Images | 3 days | The presence or absence of uptake spot in bladder wall of 89Zr-girentuximab bladder and whole body PET/CT Images. |
| Number of Patients With Positive and Negative 89Zr-girentuximab Blood Dosing | 2 days | 89Zr-girentuximab activity dosing in blood is measured. The number of patients with Positive and negative 89Zr-girentuximab Blood dosing is evaluated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events | 30 days | Serious adverse events, related or not to 89Zr-girentuximab, are assessed up to Day 30 after 89Zr-girentuximab administration, using CTC-AE scale version 5.0 |
| Number of Patients With Positive and Negative CA-IX Expression in Tumor Cells | 3 months | The expression of CAIX is by immunohistochemistry in tumor sample from TransUrethral Resection of Bladder Tumor (TURBT) or cystectomy |
| Number of Participants With Adverse Events Related to 89Zr-girentuximab | 3 days | Adverse events related to 89Zr-girentuximab are assessed up to Day 3 After 89Zr-girentuximab Administration, using CTC-AE scale version 5.0 |
| Radiation Protection Management | 3 days | Radiation exposure of 3 staff membres (extremities and Whole body: µSv). A value greater than 4mSv is considered abnormal. |
Countries
France
Participant flow
Recruitment details
Study start date First patient was enrolled: 15 DEC 2021 End of trial date (last visit of last patient): 26 SEP 2022
Pre-assignment details
All screened patients have been enrolled
Participants by arm
| Arm | Count |
|---|---|
| 89Zr-TLX250 89Zr-TLX250 (89Zr-girentuximab) PET/CT performed for all patients after 89Zr-TLX250 (89Zr-girentuximab) administration | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | 89Zr-TLX250 | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 6 Participants | — |
| Age, Categorical Between 18 and 65 years | 0 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment France | 6 Participants | — |
| Sex: Female, Male Female | 2 Participants | — |
| Sex: Female, Male Male | 4 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 1 / 6 |
| serious Total, serious adverse events | 2 / 6 |
Outcome results
Primary
Number of Participants With Uptake Spot in 89Zr-girentuximab PET/CT Images
The presence or absence of uptake spot in bladder wall of 89Zr-girentuximab bladder and whole body PET/CT Images.
Time frame: 3 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 89Zr-TLX250 (89Zr-girentuximab) PET/CT | Number of Participants With Uptake Spot in 89Zr-girentuximab PET/CT Images | Uptake spot in bladder wall with early recurrence | 1 Participants |
| 89Zr-TLX250 (89Zr-girentuximab) PET/CT | Number of Participants With Uptake Spot in 89Zr-girentuximab PET/CT Images | Uptake spot in bladder wall with post-TURB inflammatory scarring reaction | 2 Participants |
| 89Zr-TLX250 (89Zr-girentuximab) PET/CT | Number of Participants With Uptake Spot in 89Zr-girentuximab PET/CT Images | No uptake spot in bladder wall | 3 Participants |
Primary
Number of Patients With Positive and Negative 89Zr-girentuximab Blood Dosing
89Zr-girentuximab activity dosing in blood is measured. The number of patients with Positive and negative 89Zr-girentuximab Blood dosing is evaluated.
Time frame: 2 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 89Zr-TLX250 (89Zr-girentuximab) PET/CT | Number of Patients With Positive and Negative 89Zr-girentuximab Blood Dosing | Positive 89Zr-girentuximab Blood dosing | 1 Participants |
| 89Zr-TLX250 (89Zr-girentuximab) PET/CT | Number of Patients With Positive and Negative 89Zr-girentuximab Blood Dosing | Negative 89Zr-girentuximab Blood dosing | 5 Participants |
Secondary
Number of Participants With Adverse Events Related to 89Zr-girentuximab
Adverse events related to 89Zr-girentuximab are assessed up to Day 3 After 89Zr-girentuximab Administration, using CTC-AE scale version 5.0
Time frame: 3 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 89Zr-TLX250 (89Zr-girentuximab) PET/CT | Number of Participants With Adverse Events Related to 89Zr-girentuximab | Urethral bleeding grade 1 not related to 89Zr-TLX250 (89Zr-girentuximab) PET/CT | 1 Participants |
| 89Zr-TLX250 (89Zr-girentuximab) PET/CT | Number of Participants With Adverse Events Related to 89Zr-girentuximab | No adverse events | 5 Participants |
Secondary
Number of Participants With Serious Adverse Events
Serious adverse events, related or not to 89Zr-girentuximab, are assessed up to Day 30 after 89Zr-girentuximab administration, using CTC-AE scale version 5.0
Time frame: 30 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 89Zr-TLX250 (89Zr-girentuximab) PET/CT | Number of Participants With Serious Adverse Events | Urinary retention grade 2 not related to 89Zr-TLX250 (89Zr-girentuximab) PET/CT | 1 Participants |
| 89Zr-TLX250 (89Zr-girentuximab) PET/CT | Number of Participants With Serious Adverse Events | Haemorrhage grade 3 not related to 89Zr-TLX250 (89Zr-girentuximab) PET/CT | 1 Participants |
| 89Zr-TLX250 (89Zr-girentuximab) PET/CT | Number of Participants With Serious Adverse Events | No SAE | 4 Participants |
Secondary
Number of Patients With Positive and Negative CA-IX Expression in Tumor Cells
The expression of CAIX is by immunohistochemistry in tumor sample from TransUrethral Resection of Bladder Tumor (TURBT) or cystectomy
Time frame: 3 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 89Zr-TLX250 (89Zr-girentuximab) PET/CT | Number of Patients With Positive and Negative CA-IX Expression in Tumor Cells | Positive CA-IX expression in tumor cells | 5 Participants |
| 89Zr-TLX250 (89Zr-girentuximab) PET/CT | Number of Patients With Positive and Negative CA-IX Expression in Tumor Cells | Negative CA-IX expression in tumor cells | 1 Participants |
Secondary
Radiation Protection Management
Radiation exposure of 3 staff membres (extremities and Whole body: µSv). A value greater than 4mSv is considered abnormal.
Time frame: 3 days
Population: Assessments were conducted on three staff members involved in the administration of 89Zr-TLX250 (89Zr-girentuximab) to determine the presence or absence of staff contamination from the administered radioactivity during patient management.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 89Zr-TLX250 (89Zr-girentuximab) PET/CT | Radiation Protection Management | Extremities radiation exposure of staff | 5 µSv |
| 89Zr-TLX250 (89Zr-girentuximab) PET/CT | Radiation Protection Management | Whole body radiation exposure of staff | 5.5 µSv |
Secondary
Radiation Protection Management
Radiopharmaceutical management from intravesical instillation to elimination (surfasic contamination measured in counts/second).
Time frame: 1 day
Population: Measurement of radioactivity on the urinary catheter, cotton swabs, diapers, and gloves to assess potential radioactivity contamination.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 89Zr-TLX250 (89Zr-girentuximab) PET/CT | Radiation Protection Management | 115 counts per second |