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

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ClinicalTrials.gov Identifier: NCT03827317
Recruitment Status : Recruiting
First Posted : February 1, 2019
Last Update Posted : August 21, 2019
Sponsor:
Collaborators:
Medical Research Council
University of Cambridge
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Breast Cancer Radiation: [18F]GE-226 Not Applicable

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Non-randomised cohort
Masking: None (Open Label)
Primary Purpose: Other
Official Title: HERPET: A Mechanistic Non‐Invasive Imaging Study of HER2 Expression in Breast Cancer Using [18F]GE‐226 Positron Emission Tomography
Actual Study Start Date : March 8, 2019
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
HER2 positive metastatic breast cancer
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.
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.

HER2 negative metastatic breast cancer
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.
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 :
  1. 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 HER2 positive and HER2 negative breast cancer measured using SUV and AUC.

  2. Tumoral uptake of [18F]GE‐226 in patients with breast cancer measured using fully quantitative parameters [ Time Frame: 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 :
  1. Adverse events of [18F]GE-226 injection [ Time Frame: 0 hour, 48 hours ]
    Safety of [18F]GE‐226 measured by adverse events from administration of [18F]GE‐226 injection throughout the study period.

  2. Serum biochemistry change from baseline measurement [ Time Frame: 0 hour, 48 hours ]
    Safety of [18F]GE-226 injection measured by clinically significant changes from baseline measurements in serum biochemistry finding.

  3. Haematology change from baseline measurement [ Time Frame: 0 hour, 48 hours ]
    Safety of [18F]GE-226 injection measured by haematology change from baseline measurements.

  4. Immunology change from baseline measurement [ Time Frame: 0 hour, 48 hours ]
    Safety of [18F]GE-226 injection measured by clinically significant changes from baseline measurements in immunology

  5. Urine change from baseline measurement [ Time Frame: 0 hour, 48 hours ]
    Safety of [18F]GE-226 injection measured by clinically significant changes from baseline measurements in urine

  6. EEG change from baseline measurement [ Time Frame: 0 hour, 48 hours ]
    Safety of [18F]GE-226 injection measured by clinically significant changes from baseline measurements in ECG



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Female patients with a histological diagnosis of breast cancer with known HER2 status ((8 positive and 8 negative).
Accepts Healthy Volunteers:   No
Criteria

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03827317


Contacts
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Contact: HERPET Trial Coordinator 0207 59 42804 herpet@imperial.ac.uk; g.gopalakrishnan@imperial.ac.uk
Contact: Gosala Gopalakrishnan, PhD 0207 59 42804 g.gopalakrishnan@imperial.ac.uk

Locations
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United Kingdom
Imperial College Healthcare NHS Trust Recruiting
London, United Kingdom, W12 0NN
Contact: Gosala Gopalakrishnan, PhD    0207 59 42804    g.gopalakrishnan@imperial.ac.uk   
Principal Investigator: Laura M Kenny, MBBS         
Sponsors and Collaborators
Imperial College London
Medical Research Council
University of Cambridge
Investigators
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Principal Investigator: Laura M Kenny, MD FRCP PhD Imperial College London
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Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT03827317    
Other Study ID Numbers: 2015‐004027‐31
First Posted: February 1, 2019    Key Record Dates
Last Update Posted: August 21, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Imperial College London:
HER2
imaging
PET
positron emission tomography
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases