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

Not Applicable

Recruiting

• Conditions: Breast Cancer
• Interventions: Radiation: [18F]GE-226

• Registration Number: NCT03827317
• Lead Sponsor: Imperial College London

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

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-01-17
• Study First Submitted QC: 2019-01-31
• Study First Posted: 2019-02-01
• Study Start: 2019-03-08
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-23
• Last Update Posted: 2024-08-26
• Primary Completion: 2026-03-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 24

Inclusion Criteria

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

2. Written informed consent prior to admission in the study.

3. Target lesion diameter of ≥15mm that has not been previously irradiated.

4. Female patients aged ≥ 18 years of age.

5. 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).

6. ECOG performance status 0-2

7. 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

8. Life expectancy > 3 months

9. 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

10. Patients must have been appropriately staged using FDG-PET within 42 days of study entry and additional imaging according to local standard of care

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Exclusion Criteria

1. Pregnant or lactating women.
2. History of cardiac disease (myocardial infarction, arrhythmias requiring therapy, symptomatic valvular disease, cardiomyopathy, or pericarditis).
3. 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.
4. Participants with severe claustrophobia or who are unable to lie flat or fit into the scanner (≥350 lbs (160 Kg)).
5. Prior use within 14 days of enrolment or concurrent therapy with any other investigational agent.
6. Patients classified as radiation workers
7. Patients on therapeutic doses of anticoagulants, or with a raised prothrombin time

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HER2 negative metastatic breast cancer	[18F]GE-226	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.
HER2 positive metastatic breast cancer	[18F]GE-226	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.

Primary Outcome Measures

Name	Time	Method
Tumoral uptake of [18F]GE-226 in patients with breast cancer measured using semi-quantitative parameters	24 months	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	24 months	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

Name	Time	Method
Adverse events of [18F]GE-226 injection	0 hour, 48 hours	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	0 hour, 48 hours	Safety of \[18F\]GE-226 injection measured by clinically significant changes from baseline measurements in serum biochemistry finding.
Haematology change from baseline measurement	0 hour, 48 hours	Safety of \[18F\]GE-226 injection measured by haematology change from baseline measurements.
Immunology change from baseline measurement	0 hour, 48 hours	Safety of \[18F\]GE-226 injection measured by clinically significant changes from baseline measurements in immunology
Urine change from baseline measurement	0 hour, 48 hours	Safety of \[18F\]GE-226 injection measured by clinically significant changes from baseline measurements in urine
EEG change from baseline measurement	0 hour, 48 hours	Safety of \[18F\]GE-226 injection measured by clinically significant changes from baseline measurements in ECG

Trial Locations

Locations (1)

Imperial College Healthcare NHS Trust; 🇬🇧 London, United Kingdom