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

Primary Purpose

Breast Neoplasms, Secondary, HER2 Positive Carcinoma of Breast

Status
Completed
Phase
Phase 1
Locations
Belgium
Study Type
Interventional
Intervention
Zr89-trastuzumab
Sponsored by
Jules Bordet Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Breast Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Jules Bordet Institut

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Zr89-trastuzumab PET/CT

Arm Description

Zr89-trastuzumab PET/CT single arm

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Time Activity Curve
Time activity curve of normal organ and tumor lesions: pharmacokinetic
HER2 Extracellular Domain
evaluate the concentration of circulating HER2 extracellular domain in the blood and study his possible role as on imaging quality

Full Information

First Posted
August 8, 2011
Last Updated
March 7, 2017
Sponsor
Jules Bordet Institute
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1. Study Identification

Unique Protocol Identification Number
NCT01420146
Brief Title
Pilot Imaging Study With 89Zr-Trastuzumab in HER2-positive Metastatic Breast Cancer Patients
Acronym
IJBMNZrT003
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

2. Study Status

Record Verification Date
January 2015
Overall Recruitment Status
Completed
Study Start Date
August 2011 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jules Bordet Institute

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Neoplasms, Secondary, HER2 Positive Carcinoma of Breast

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Zr89-trastuzumab PET/CT
Arm Type
Experimental
Arm Description
Zr89-trastuzumab PET/CT single arm
Intervention Type
Drug
Intervention Name(s)
Zr89-trastuzumab
Other Intervention Name(s)
HER2 ImmunoPET/CT, HER2 receptor imaging, Breast cancer molecular imaging
Intervention Description
trastuzumab labelled with zirconium 89 for PET/CT
Primary Outcome Measure Information:
Title
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
Description
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).
Time Frame
4 years
Secondary Outcome Measure Information:
Title
Time Activity Curve
Description
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
Title
HER2 Extracellular Domain
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: 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). 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. Patients with FDG-PET positive metastatic lesions. Brain metastases are allowed provided they are controlled and they are not the sole site of metastatic disease. Patient planned to have metastatic site biopsy for HER2 status control. Age ≥ 18 years Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1 For women of childbearing potential a pregnancy test will be done and an agreement to use a highly-effective non hormonal form of contraception. Agreement from the patient to participate in this imaging study and if indicated agreement to biopsy one or two accessible lesions. Signed written informed consent (approved by the Ethics Committee) obtained prior to any study procedure Exclusion criteria: Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) Pregnant or lactating women Current known infection with HIV, HBV, or HCV Known severe hypersensitivity to trastuzumab Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol Patients with bone only metastases are not eligible Psychiatric illness/social situations that would limit compliance with study requirements Patients who received lapatinib within the 7 days prior to HER immunoPET/CT.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick Flamen, MD, PhD
Organizational Affiliation
Jules Bordet Institut
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jules Bordet Institut
City
Brussels
ZIP/Postal Code
1000
Country
Belgium

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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