Clinical trial NCT01420146: Pilot Imaging Study With 89Zr-Trastuzumab in HER2-positive Metastatic Breast Cancer Patients
Official title: Pilot Imaging Study With 89Zr-Trastuzumab in HER2-positive Metastatic Breast Cancer Patients : Correlation With FDG-PET/CT and Anatomopathological Results
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Neoplasms
Secondary
HER2 Positive Carcinoma of Breast
Lead sponsor: Jules Bordet Institute
Sponsor class: OTHER
First posted: 2011-08-19
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 4 years
Secondary outcomes:
measure: Time Activity Curve
timeFrame: 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
measure: HER2 Extracellular Domain
timeFrame: within 60 min before tracer injection
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Jules Bordet Institut
Study officials:
affiliation: Jules Bordet Institut
name: Patrick Flamen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: