Imaging Performance Assessment of 89Zirconium-labelled Girentuximab (89Zr-TLX250) PET-CT in Metastatic Triple Negative Breast Cancer Patients

Study Overview
=================
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 tracer for the imaging of metastatic triple negative breast cancer (TNBC) patients.

Detailed Description
-----------------
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 tracer for the imaging of metastatic triple negative breast cancer (TNBC) patients. TNBC patients are known to be rapidly progressive and have a poor prognosis. This poor prognosis is due to the lack of common breast cancer targets in TNBC. As TNBC expresses CAIX, this stuy will evaluate CAIX targeting by using a radiolabeled monoclonal antibody that recognizes carbonic anhydrase IX (CAIX) : 89Zr- girentuximab otherwise known as 89Zr-TLX250. Previous and ongoing studies have demonstrated the potential application of 89Zr-TLX250 as a new PET/CT imaging tracer for the detection of renal cancer. After establishing the TNBC targeting properties of the 89Zr-TLX250 PET/CT imaging tracer, it should be interesting to develop a new targeted therapy using TLX250- radiolabeled with a therapeutic radionuclide such as 177Lutétium.

Official Title
-----------------
Prospective Phase II Pilot Study, Assessing Imaging Performance of 89Zirconium-labelled Girentuximab (89Zr-TLX250) PET-CT (Positron Emission Tomography/Computerized Tomography) in Metastatic Triple Negative Breast Cancer Patients

Conditions
-----------------
Triple Negative Breast Cancer

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations. Female or male, Age ≥ 18 years at time of study entry. Primitive triple negative breast cancer proven histologically, defined according to the following criteria: Estrogen receptors <10%. And progesterone receptors <10%. And Human Epidermal Growth factor Receptor 2 (HER2) not amplified or not overexpressed. Breast Cancer (BC) recurrence documented by conventional imaging and/or FDG PET/CT with at least one measurable metastatic lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) and/or PET Response Criteria In Solid Tumors (PERCIST). Consent to use a contraception method for at least 30 days after administration of 89Zr-TLX250. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1. Life expectancy at least 6 months. Patient has valid health insurance. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. Exclusion Criteria: History of another primary malignancy except for basal cell carcinoma within the last 5 years. 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). Planned antineoplastic therapies (for the period between IV administration of 89Zr-TLX250 and imaging). Exposure to murine or chimeric antibodies within the last 5 years. Previous administration of any radionuclide within 10 half-lives of the same. Impossibility to hold lying motionless at least 1 hour, or known claustrophobia. Serious non-malignant disease (e.g. psychiatric, infectious, autoimmune or metabolic), that may interfere with the objectives of the study or with the safety or compliance of the subject, as judged by the investigator. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study. Pregnant or likely to be pregnant or nursing patient. Known hypersensitivity to girentuximab or desferoxamine. Renal insufficiency with Glomerular Filtration Rate : GFR ≤ 45 mL/min/ 1.73 m². Persons deprived of their liberty, under a measure of safeguard of justice, under guardianship or placed under the authority of a guardian. Disorder precluding understanding of trial information or informed consent.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the concordance for tumor lesion detection using 89Zr-TLX250 PET/CT versus a conventional 18FDG PET/CT scan | Assess the concordance for tumor lesion detection using 89Zr-TLX250 PET/CT scan : Positron Emission Tomography/Computerized Tomography scan versus a conventional 18 Fluorodésoxyglucose (18FDG) PET/CT scan where comparison will be made on a per lesion analysis basis | 35 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| determine the percent of total tumor burden (whole body) detected on 89Zr-TLX250 PET/CT scan compared to that defined on 18FDG PET/CT used as the reference | Percent of positive CA IX metastatic tumor burden compared to total metastatic tumor burden by 18FDG (ratio Number of positive 89Zr-TLX250 lesions / Number of positive FDG lesions | 35 days | 
| Assess the correlation between the Standardized Uptake Values (SUV) of 89Zr-TLX250 and CAIX histological expression if a biopsy is done | If a metastasis biopsy is conducted, assessment of the correlation between the normalized uptake values (SUV) of 89Zr-TLX250 positive lesions and CAIX histological expression will be done by comparing the 89Zr-TLX250 semi-quantitative data with the immunohistochemical results (IHC) of biopsied metastases | 35 days | 
| Vital signs measurment after 89Zr-TLX250 injection | Vital signs will be measured within 2 hours after 89Zr-TLX250 injection | 2 Hours | 
| Assess the generation of Human Anti-Chimeric Antibodies (HACA) in response to the girentuximab | A blood sample will be drawn before 89Zr-TLX250 injection and 3 months after in order to evaluate the presence of Human anti-chimeric antibody (HACA) in sera of patients. This will be tested quantitatively and qualitatively using validated ELISAs HACA | 3 months | 
| Number of participants with adverse events and Serious Adverse Events related to 89Zr-TLX250 as assessed by CTCAE v5.0 | All Adverse Events and Serious Adverse Events due to 89Zr-TLX250 will be reported | 30 days | 
| Number of participants with Serious Adverse Events related to 89Zr-TLX250 as assessed by CTCAE v5.0 | All Serious Adverse Events due to 89Zr-TLX250 will be reported | 30 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
89Zr-TLX250 (89Zirconium-TLX250), Positron Emission Tomography/Computerized Tomography (PET/CT) scan, carbonic anhydrase IX (CAIX), 89Zr- girentuximab (89Zirconium-girentuximab), 89Zr-TLX250 PET/CT, Metastatic Triple Negative Breast Cancer (TNBC), Human Anti-Chimeric Antibodies (HACA)