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

Overview

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

Interventions

• Radiation [18F]GE-226
  \[18F\]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 measures

• Tumoral uptake of [18F]GE-226 in patients with breast cancer measured using semi-quantitative parameters [Time frame: 24 months]
• Tumoral uptake of [18F]GE-226 in patients with breast cancer measured using fully quantitative parameters [Time frame: 24 months]

Secondary outcome measures (6)

• Adverse events of [18F]GE-226 injection [Time frame: 0 hour, 48 hours]
• Serum biochemistry change from baseline measurement [Time frame: 0 hour, 48 hours]
• Haematology change from baseline measurement [Time frame: 0 hour, 48 hours]
• Immunology change from baseline measurement [Time frame: 0 hour, 48 hours]
• Urine change from baseline measurement [Time frame: 0 hour, 48 hours]
• EEG change from baseline measurement [Time frame: 0 hour, 48 hours]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Other

Study locations

United Kingdom · 1 center

• Imperial College Healthcare NHS Trust — London

Identifiers

NCT: NCT03827317 · 2015-004027-31

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗