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HERPET- A Novel PET Imaging Study of HER2 in Breast Cancer

Primary Purpose

Breast Cancer

Status

Recruiting

Phase

Not Applicable

Locations

United Kingdom

Study Type

Interventional

Intervention

[18F]GE-226

About this trial

This is an interventional other trial for Breast Cancer focused on measuring HER2, imaging, PET, positron emission tomography

Eligibility Criteria

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

Inclusion Criteria:

Female patients with a histological diagnosis of breast cancer with known HER2 status ((8 positive and 8 negative).
Written informed consent prior to admission in the study.
Target lesion diameter of ≥15mm that has not been previously irradiated.
Female patients aged ≥ 18 years of age.
For all patients: histologically confirmed locally advanced/metastatic breast cancer with a biopsy within the last 12 months confirming HER2 status by either immunohistochemistry (IHC), Silver In Situ Hybridization (SISH) or Fluorescent In Situ Hybridization (FISH).
ECOG performance status 0-2
Negative urine pregnancy test (within 2 hours prior to injection of imaging agent) in women of child bearing age and willingness to use contraception (barrier, abstinence, non-hormonal) for 3 weeks after injection of [18F]GE-226
Life expectancy > 3 months
Adequate organ function as defined by
- Hb≥10g/L
- WBC≥3.0 x 109/L
- PLT≥80 x 109/L
- Serum creatinine ≤1.4mg/dl
- SGOT and SGPT ≤2 x ULN
- Total bilirubin ≤ 2 x ULN or 3.0 mg/dl in patients with Gilbert's syndrome
Patients must have been appropriately staged using FDG-PET within 42 days of study entry and additional imaging according to local standard of care

Exclusion Criteria:

Pregnant or lactating women.
History of cardiac disease (myocardial infarction, arrhythmias requiring therapy, symptomatic valvular disease, cardiomyopathy, or pericarditis).
Evidence of significant medical condition or laboratory finding which, in the opinion of the Investigator, makes it undesirable for the patient to participate in the trial.
Participants with severe claustrophobia or who are unable to lie flat or fit into the scanner (≥350 lbs (160 Kg)).
Prior use within 14 days of enrolment or concurrent therapy with any other investigational agent.
Patients classified as radiation workers
Patients on therapeutic doses of anticoagulants, or with a raised prothrombin time

Sites / Locations

Imperial College Healthcare NHS TrustRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

HER2 positive metastatic breast cancer

HER2 negative metastatic breast cancer

Arm Description

8 HER2 positive patients (determined using the most recent biopsy) will be recruited. Dynamic [18F]GE-226 PET imaging over 90 minutes, radial artery sampling will be performed to establish the pharmacokinetic profile of [18F]GE-226 and hence determine the optimal imaging time point for [18F]GE-226 PET scans. Tumour uptake in individual metastases (and the target lesion) will be reported. Uptake will be compared between HER2 positive and negative tumours.

8 HER2 negative patients (determined using the most recent biopsy) will be recruited. Dynamic [18F]GE-226 PET imaging over 90 minutes, radial artery sampling will be performed to establish the pharmacokinetic profile of [18F]GE-226 and hence determine the optimal imaging time point for [18F]GE-226 PET scans. Tumour uptake in individual metastases (and the target lesion) will be reported. Uptake will be compared between HER2 positive and negative tumours.

Outcomes

Primary Outcome Measures

Tumoral uptake of [18F]GE-226 in patients with breast cancer measured using semi-quantitative parameters

Tumoral uptake of [18F]GE-226 in patients with HER2 positive and HER2 negative breast cancer measured using SUV and AUC.

Tumoral uptake of [18F]GE-226 in patients with breast cancer measured using fully quantitative parameters

Tumoral uptake of [18F]GE-226 in patients with HER2 positive and HER2 negative breast cancer measured using Ki in the case or irreversible uptake, and binding potential in the case of reversible uptake.

Secondary Outcome Measures

Adverse events of [18F]GE-226 injection

Safety of [18F]GE-226 measured by adverse events from administration of [18F]GE-226 injection throughout the study period.

Serum biochemistry change from baseline measurement

Safety of [18F]GE-226 injection measured by clinically significant changes from baseline measurements in serum biochemistry finding.

Haematology change from baseline measurement

Safety of [18F]GE-226 injection measured by haematology change from baseline measurements.

Immunology change from baseline measurement

Safety of [18F]GE-226 injection measured by clinically significant changes from baseline measurements in immunology

Urine change from baseline measurement

Safety of [18F]GE-226 injection measured by clinically significant changes from baseline measurements in urine

EEG change from baseline measurement

Safety of [18F]GE-226 injection measured by clinically significant changes from baseline measurements in ECG

Full Information

NCT ID

NCT03827317

First Posted

January 17, 2019

Last Updated

January 3, 2023

Sponsor

Imperial College London

Collaborators

Medical Research Council, University of Cambridge

1. Study Identification

Unique Protocol Identification Number

NCT03827317

Brief Title

HERPET- A Novel PET Imaging Study of HER2 in Breast Cancer

Official Title

HERPET: A Mechanistic Non-Invasive Imaging Study of HER2 Expression in Breast Cancer Using [18F]GE-226 Positron Emission Tomography

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 8, 2019 (Actual)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Imperial College London

Collaborators

Medical Research Council, University of Cambridge

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This mechanistic study will be the first study to assess the efficacy of [18F]GE-226 to target HER2 expression in patients with metastatic breast cancer. The study will establish the pharmacokinetics of [18F]GE-226 and the optimum time-point for performing static scans in this patient population.

Detailed Description

Objectives Primary: To determine the uptake in tumour lesions and normal tissue of [18F]GE-226 and compare the difference between patients with HER2 positive and HER2 negative lesions. Uptake will be quantified by semi-quantitative (SUV, AUC) and fully quantitative parameters (Ki in the case of irreversible uptake, and binding potential in the case of reversible uptake) To determine the optimal imaging time point for [18F]GE-226 Secondary: To determine the safety and toxicity of [18F]GE-226 PET in humans To determine if [18F]GE-226 can distinguish between HER2 amplified and HER2 non-amplified breast tumours To determine the metabolism of [18F]GE-226 in human subjects Exploratory: • To explore circulating biomarkers that may be related to [18F]GE-226 uptake and to investigate if treatment modulates [18F]GE-226 Endpoints Secondary: Safety and toxicity of [18F]GE-226 measured by adverse events from administration of [18F]GE-226 injection throughout the study period, and clinically significant changes from baseline measurements in serum biochemistry, haematology, coagulation, immunology, urinalysis, vital signs, ECG, injection site and physical examination findings. The association between [18F]GE-226 tumour uptake and standard HER2 pathological testing (HER2 amplified and HER2 non-amplified breast tumours) Proportion of metabolised [18F]GE-226 at scheduled time-points compared to baseline Normal tissue uptake of [18F]GE-226 will be quantified in the appropriate regions depending on the field of view. Exploratory: • To perform preliminary biodistribution analysis, to compare [18F]GE- 226 uptake to [18F]FDG uptake in tumour lesion

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

HER2, imaging, PET, positron emission tomography

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

Non-randomised cohort

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

HER2 positive metastatic breast cancer

Arm Type

Other

Arm Description

Arm Title

HER2 negative metastatic breast cancer

Arm Type

Other

Arm Description

Intervention Type

Radiation

Intervention Name(s)

[18F]GE-226

Intervention Description

[18F]GE-226 is a radiolabelled Affibody® tracer which binds to the HER2 receptor with high affinity at a different epitope than trastuzumab. The active molecule is a 61 amino acid peptide that is modified site-specifically with one fluorobenzaldehyde molecule at the C-terminal.

Primary Outcome Measure Information:

Title

Tumoral uptake of [18F]GE-226 in patients with breast cancer measured using semi-quantitative parameters

Description

Tumoral uptake of [18F]GE-226 in patients with HER2 positive and HER2 negative breast cancer measured using SUV and AUC.

Time Frame

24 months

Title

Tumoral uptake of [18F]GE-226 in patients with breast cancer measured using fully quantitative parameters

Description

Time Frame

24 months

Secondary Outcome Measure Information:

Title

Adverse events of [18F]GE-226 injection

Description

Safety of [18F]GE-226 measured by adverse events from administration of [18F]GE-226 injection throughout the study period.

Time Frame

0 hour, 48 hours

Title

Serum biochemistry change from baseline measurement

Description

Safety of [18F]GE-226 injection measured by clinically significant changes from baseline measurements in serum biochemistry finding.

Time Frame

0 hour, 48 hours

Title

Haematology change from baseline measurement

Description

Safety of [18F]GE-226 injection measured by haematology change from baseline measurements.

Time Frame

0 hour, 48 hours

Title

Immunology change from baseline measurement

Description

Safety of [18F]GE-226 injection measured by clinically significant changes from baseline measurements in immunology

Time Frame

0 hour, 48 hours

Title

Urine change from baseline measurement

Description

Safety of [18F]GE-226 injection measured by clinically significant changes from baseline measurements in urine

Time Frame

0 hour, 48 hours

Title

EEG change from baseline measurement

Description

Safety of [18F]GE-226 injection measured by clinically significant changes from baseline measurements in ECG

Time Frame

0 hour, 48 hours

10. Eligibility

Sex

Female

Gender Based

Yes

Gender Eligibility Description

Female patients with a histological diagnosis of breast cancer with known HER2 status ((8 positive and 8 negative).

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Female patients with a histological diagnosis of breast cancer with known HER2 status ((8 positive and 8 negative). Written informed consent prior to admission in the study. Target lesion diameter of ≥15mm that has not been previously irradiated. Female patients aged ≥ 18 years of age. For all patients: histologically confirmed locally advanced/metastatic breast cancer with a biopsy within the last 12 months confirming HER2 status by either immunohistochemistry (IHC), Silver In Situ Hybridization (SISH) or Fluorescent In Situ Hybridization (FISH). ECOG performance status 0-2 Negative urine pregnancy test (within 2 hours prior to injection of imaging agent) in women of child bearing age and willingness to use contraception (barrier, abstinence, non-hormonal) for 3 weeks after injection of [18F]GE-226 Life expectancy > 3 months Adequate organ function as defined by Hb≥10g/L WBC≥3.0 x 109/L PLT≥80 x 109/L Serum creatinine ≤1.4mg/dl SGOT and SGPT ≤2 x ULN Total bilirubin ≤ 2 x ULN or 3.0 mg/dl in patients with Gilbert's syndrome Patients must have been appropriately staged using FDG-PET within 42 days of study entry and additional imaging according to local standard of care Exclusion Criteria: Pregnant or lactating women. History of cardiac disease (myocardial infarction, arrhythmias requiring therapy, symptomatic valvular disease, cardiomyopathy, or pericarditis). Evidence of significant medical condition or laboratory finding which, in the opinion of the Investigator, makes it undesirable for the patient to participate in the trial. Participants with severe claustrophobia or who are unable to lie flat or fit into the scanner (≥350 lbs (160 Kg)). Prior use within 14 days of enrolment or concurrent therapy with any other investigational agent. Patients classified as radiation workers Patients on therapeutic doses of anticoagulants, or with a raised prothrombin time

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

HERPET Trial Coordinator

Phone

0207 59 42804

herpet@imperial.ac.uk; g.gopalakrishnan@imperial.ac.uk

First Name & Middle Initial & Last Name or Official Title & Degree

Gosala Gopalakrishnan, PhD

Phone

0207 59 42804

g.gopalakrishnan@imperial.ac.uk

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Laura M Kenny, MD FRCP PhD

Organizational Affiliation

Imperial College London

Official's Role

Principal Investigator

Facility Information:

Facility Name

Imperial College Healthcare NHS Trust

City

London

ZIP/Postal Code

W12 0NN

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Gosala Gopalakrishnan, PhD

Phone

0207 59 42804

g.gopalakrishnan@imperial.ac.uk

First Name & Middle Initial & Last Name & Degree

Laura M Kenny, MBBS

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

HERPET- A Novel PET Imaging Study of HER2 in Breast Cancer

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