Breast Neoplasms, HER2 Positive Carcinoma of Breast, Secondary
Conditions
Brief summary
Evaluation of the diagnostic potential of HER2 imaging using zirconium 89 labelled trastuzumab.
Detailed description
This is the first belgian feasibility study of HER2 imaging using a labelled monoclonal antibody, namely trastuzumab labelled with zirconium 89. The aims of this study are: I/ Evaluate the diagnostic potential of HER2 imaging using zirconium 89 labelled trastuzumab (based on the Groningen experience), through the analysis of the correlation between the FDG-PET/CT and the HER2 immunoPET. II/ PET quantification of HER2 receptor by using the images and the blood pharmacokinetic of the tracer. III/ In the subset of patients for whom biopsies of metastatic sites have not been carried out previously and are of an easy access, tissue will be acquired as part of the validation of the HER2 immunoPET and as an attempt to better understand the molecular heterogeneity of HER2 positive breast cancer at the time of relapse. IV/Evaluate the concentration of circulating HER2 extracellular domain in the blood and study his possible role as on imaging quality
Interventions
DRUGZr89-trastuzumab
trastuzumab labelled with zirconium 89 for PET/CT
Sponsors
Jules Bordet Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. All patients selected for this imaging study are patients scheduled to start trastuzumab-based therapy for advanced HER2 positive breast cancer (This includes trastuzumab alone, trastuzumab + chemotherapy, trastuzumab + endocrine therapy). 2. Histologically confirmed HER 2 positive (defined as FISH amplification ratio more than 2.2) invasive carcinoma of the breast (primary tumor at diagnosis) with locally recurrent or metastatic disease. 3. Patients with FDG-PET positive metastatic lesions. 4. Brain metastases are allowed provided they are controlled and they are not the sole site of metastatic disease. 5. Patient planned to have metastatic site biopsy for HER2 status control. 6. Age ≥ 18 years 7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1 8. For women of childbearing potential a pregnancy test will be done and an agreement to use a highly-effective non hormonal form of contraception. 9. Agreement from the patient to participate in this imaging study and if indicated agreement to biopsy one or two accessible lesions. 10. Signed written informed consent (approved by the Ethics Committee) obtained prior to any study procedure
Exclusion criteria
1. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) 2. Pregnant or lactating women 3. Current known infection with HIV, HBV, or HCV 4. Known severe hypersensitivity to trastuzumab 5. Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol 6. Patients with bone only metastases are not eligible 7. Psychiatric illness/social situations that would limit compliance with study requirements 8. Patients who received lapatinib within the 7 days prior to HER immunoPET/CT.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Test the Diagnostic Accuracy of the HER2 Imaging Using the Labelled Monoclonal Antibody Trastuzumab by Correlating the HER2 PET/CT Imaging With the FDG-PET/CT and Molecular Characterization of Tumor Samples With Discordant Image Findings | 4 years | A visual 'patient-based' classification capturing the whole disease burden was developed by using a side-by-side display, comparing baseline FDG-PET/CT(showing all FDG-positive mets independent of their HER2-imaging status) & day4 HER2-PET/CT. Pts were grouped into 4 HER2-PET/CT patterns according to the proportion of FDG avid tumour load showing relevant 89Zr-T uptake. Pattern A: entire tumor load showed pertinent tracer uptake; B: dominant part of tumour load showed tracer uptake; C: minor part of tumor load showed tracer uptake; D: entire tumor load lacked tracer uptake. Patterns A+B='HER2-positive' & C+D='HER2-negative'. In the 20 pts: 4 pts were classified A, 5B, 1C & 10D. This classification indicates substantial heterogeneity of 89Zr-T uptake within this so called 'HER2-positive' pt population. After dichotomization, 11(55%) pts were considered as HER2-PET/CT negative. Furthermore, HER2-PET/CT revealed intrapatient heterogeneity of tumour uptake(pts classified B or C). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time Activity Curve | blood sample at 5, 15, 30, 60 minutes, 1 day, 2 days and 4 or 6 days after tracer injection. Images : Day 0, Day 2 and Day 4 or 6 | Time activity curve of normal organ and tumor lesions: pharmacokinetic |
| HER2 Extracellular Domain | within 60 min before tracer injection | evaluate the concentration of circulating HER2 extracellular domain in the blood and study his possible role as on imaging quality |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zr89-trastuzumab PET/CT Zr89-trastuzumab (trastuzumab labelled with zirconium 89) for PET/CT single arm | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Zr89-trastuzumab PET/CT |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Region of Enrollment Belgium | 20 Participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 20 |
| serious Total, serious adverse events | 1 / 20 |
Outcome results
Primary
Test the Diagnostic Accuracy of the HER2 Imaging Using the Labelled Monoclonal Antibody Trastuzumab by Correlating the HER2 PET/CT Imaging With the FDG-PET/CT and Molecular Characterization of Tumor Samples With Discordant Image Findings
A visual 'patient-based' classification capturing the whole disease burden was developed by using a side-by-side display, comparing baseline FDG-PET/CT(showing all FDG-positive mets independent of their HER2-imaging status) & day4 HER2-PET/CT. Pts were grouped into 4 HER2-PET/CT patterns according to the proportion of FDG avid tumour load showing relevant 89Zr-T uptake. Pattern A: entire tumor load showed pertinent tracer uptake; B: dominant part of tumour load showed tracer uptake; C: minor part of tumor load showed tracer uptake; D: entire tumor load lacked tracer uptake. Patterns A+B='HER2-positive' & C+D='HER2-negative'. In the 20 pts: 4 pts were classified A, 5B, 1C & 10D. This classification indicates substantial heterogeneity of 89Zr-T uptake within this so called 'HER2-positive' pt population. After dichotomization, 11(55%) pts were considered as HER2-PET/CT negative. Furthermore, HER2-PET/CT revealed intrapatient heterogeneity of tumour uptake(pts classified B or C).
Time frame: 4 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zr89-trastuzumab PET/CT | Test the Diagnostic Accuracy of the HER2 Imaging Using the Labelled Monoclonal Antibody Trastuzumab by Correlating the HER2 PET/CT Imaging With the FDG-PET/CT and Molecular Characterization of Tumor Samples With Discordant Image Findings | Pattern A | 4 Participants |
| Zr89-trastuzumab PET/CT | Test the Diagnostic Accuracy of the HER2 Imaging Using the Labelled Monoclonal Antibody Trastuzumab by Correlating the HER2 PET/CT Imaging With the FDG-PET/CT and Molecular Characterization of Tumor Samples With Discordant Image Findings | Pattern B | 5 Participants |
| Zr89-trastuzumab PET/CT | Test the Diagnostic Accuracy of the HER2 Imaging Using the Labelled Monoclonal Antibody Trastuzumab by Correlating the HER2 PET/CT Imaging With the FDG-PET/CT and Molecular Characterization of Tumor Samples With Discordant Image Findings | Pattern C | 1 Participants |
| Zr89-trastuzumab PET/CT | Test the Diagnostic Accuracy of the HER2 Imaging Using the Labelled Monoclonal Antibody Trastuzumab by Correlating the HER2 PET/CT Imaging With the FDG-PET/CT and Molecular Characterization of Tumor Samples With Discordant Image Findings | Pattern D | 10 Participants |
Secondary
HER2 Extracellular Domain
evaluate the concentration of circulating HER2 extracellular domain in the blood and study his possible role as on imaging quality
Time frame: within 60 min before tracer injection
Secondary
Time Activity Curve
Time activity curve of normal organ and tumor lesions: pharmacokinetic
Time frame: blood sample at 5, 15, 30, 60 minutes, 1 day, 2 days and 4 or 6 days after tracer injection. Images : Day 0, Day 2 and Day 4 or 6