Pilot Imaging Study With 89Zr-Trastuzumab in HER2-positive Metastatic Breast Cancer Patients (IJBMNZrT003)

Pilot Imaging Study With 89Zr-Trastuzumab in HER2-positive Metastatic Breast Cancer Patients : Correlation With FDG-PET/CT and Anatomopathological Results

Evaluation of the diagnostic potential of HER2 imaging using zirconium 89 labelled trastuzumab.

Study Overview

• Status: Completed
• Conditions: Breast Neoplasms; Secondary; HER2 Positive Carcinoma of Breast
• Intervention / Treatment: Drug: Zr89-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

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • Jules Bordet Institut

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zr89-trastuzumab PET/CT; Zr89-trastuzumab PET/CT single arm	Drug: Zr89-trastuzumab; trastuzumab labelled with zirconium 89 for PET/CT; Other Names: HER2 ImmunoPET/CT; HER2 receptor imaging; Breast cancer molecular imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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", 5"B", 1"C" & 10"D". 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).	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time Activity Curve	Time activity curve of normal organ and tumor lesions: pharmacokinetic	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
HER2 Extracellular Domain	evaluate the concentration of circulating HER2 extracellular domain in the blood and study his possible role as on imaging quality	within 60 min before tracer injection

Collaborators and Investigators

• Sponsor: Jules Bordet Institute
• Investigators: Principal Investigator: Patrick Flamen, MD, PhD, Jules Bordet Institut

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: August 8, 2011
• First Submitted That Met QC Criteria: August 18, 2011
• First Posted (Estimate): August 19, 2011

Study Record Updates

• Last Update Posted (Actual): April 18, 2017
• Last Update Submitted That Met QC Criteria: March 7, 2017
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: IJBMNZrT003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided