Clinical trial NCT04758780: Imaging Performance Assessment of 89Zirconium-labelled Girentuximab (89Zr-TLX250) PET-CT in Metastatic Triple Negative Breast Cancer Patients
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Triple Negative Breast Cancer
Keywords: 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)
Lead sponsor: Institut Cancerologie de l'Ouest
Sponsor class: OTHER
Collaborators: name: Telix Pharmaceutical
name: SIRIC ILIAD
First posted: 2021-02-17
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Monocentric, open prospective study
Primary purpose: DIAGNOSTIC

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.

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.

Primary outcomes:
measure: Assess the concordance for tumor lesion detection using 89Zr-TLX250 PET/CT versus a conventional 18FDG PET/CT scan
timeFrame: 35 days
Secondary outcomes:
measure: 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
timeFrame: 35 days
measure: Assess the correlation between the Standardized Uptake Values (SUV) of 89Zr-TLX250 and CAIX histological expression if a biopsy is done
timeFrame: 35 days
measure: Vital signs measurment after 89Zr-TLX250 injection
timeFrame: 2 Hours
measure: Assess the generation of Human Anti-Chimeric Antibodies (HACA) in response to the girentuximab
timeFrame: 3 months
measure: Number of participants with adverse events and Serious Adverse Events related to 89Zr-TLX250 as assessed by CTCAE v5.0
timeFrame: 30 days
measure: Number of participants with Serious Adverse Events related to 89Zr-TLX250 as assessed by CTCAE v5.0
timeFrame: 30 days
Other outcomes:
Locations:
city: Saint-Herblain
country: France
facility: ICO René Gauducheau
Study officials:
affiliation: Institut de Cancerologie de l'Ousest - ICO
name: Caroline ROUSSEAU, MD
role: STUDY_CHAIR
References: