<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03827317</url>
  </required_header>
  <id_info>
    <org_study_id>2015-004027-31</org_study_id>
    <nct_id>NCT03827317</nct_id>
  </id_info>
  <brief_title>HERPET- A Novel PET Imaging Study of HER2 in Breast Cancer</brief_title>
  <official_title>HERPET: A Mechanistic Non-Invasive Imaging Study of HER2 Expression in Breast Cancer Using [18F]GE-226 Positron Emission Tomography</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Medical Research Council</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Cambridge</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Imperial College London</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This mechanistic study will be the first study to assess the efficacy of [18F]GE-226 to&#xD;
      target HER2 expression in patients with metastatic breast cancer. The study will establish&#xD;
      the pharmacokinetics of [18F]GE-226 and the optimum time-point for performing static scans in&#xD;
      this patient population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives&#xD;
&#xD;
      Primary:&#xD;
&#xD;
        -  To determine the uptake in tumour lesions and normal tissue of [18F]GE-226 and compare&#xD;
           the difference between patients with HER2 positive and HER2 negative lesions. Uptake&#xD;
           will be quantified by semi-quantitative (SUV, AUC) and fully quantitative parameters (Ki&#xD;
           in the case of irreversible uptake, and binding potential in the case of reversible&#xD;
           uptake)&#xD;
&#xD;
        -  To determine the optimal imaging time point for [18F]GE-226&#xD;
&#xD;
      Secondary:&#xD;
&#xD;
        -  To determine the safety and toxicity of [18F]GE-226 PET in humans&#xD;
&#xD;
        -  To determine if [18F]GE-226 can distinguish between HER2 amplified and HER2&#xD;
           non-amplified breast tumours&#xD;
&#xD;
        -  To determine the metabolism of [18F]GE-226 in human subjects&#xD;
&#xD;
      Exploratory:&#xD;
&#xD;
      • To explore circulating biomarkers that may be related to [18F]GE-226 uptake and to&#xD;
      investigate if treatment modulates [18F]GE-226&#xD;
&#xD;
      Endpoints&#xD;
&#xD;
      Secondary:&#xD;
&#xD;
        -  Safety and toxicity of [18F]GE-226 measured by adverse events from administration of&#xD;
           [18F]GE-226 injection throughout the study period, and clinically significant changes&#xD;
           from baseline measurements in serum biochemistry, haematology, coagulation, immunology,&#xD;
           urinalysis, vital signs, ECG, injection site and physical examination findings.&#xD;
&#xD;
        -  The association between [18F]GE-226 tumour uptake and standard HER2 pathological testing&#xD;
           (HER2 amplified and HER2 non-amplified breast tumours)&#xD;
&#xD;
        -  Proportion of metabolised [18F]GE-226 at scheduled time-points compared to baseline&#xD;
&#xD;
        -  Normal tissue uptake of [18F]GE-226 will be quantified in the appropriate regions&#xD;
           depending on the field of view.&#xD;
&#xD;
      Exploratory:&#xD;
&#xD;
      • To perform preliminary biodistribution analysis, to compare [18F]GE- 226 uptake to [18F]FDG&#xD;
      uptake in tumour lesion&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 8, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Non-randomised cohort</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Tumoral uptake of [18F]GE-226 in patients with breast cancer measured using semi-quantitative parameters</measure>
    <time_frame>24 months</time_frame>
    <description>Tumoral uptake of [18F]GE-226 in patients with HER2 positive and HER2 negative breast cancer measured using SUV and AUC.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tumoral uptake of [18F]GE-226 in patients with breast cancer measured using fully quantitative parameters</measure>
    <time_frame>24 months</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse events of [18F]GE-226 injection</measure>
    <time_frame>0 hour, 48 hours</time_frame>
    <description>Safety of [18F]GE-226 measured by adverse events from administration of [18F]GE-226 injection throughout the study period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum biochemistry change from baseline measurement</measure>
    <time_frame>0 hour, 48 hours</time_frame>
    <description>Safety of [18F]GE-226 injection measured by clinically significant changes from baseline measurements in serum biochemistry finding.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Haematology change from baseline measurement</measure>
    <time_frame>0 hour, 48 hours</time_frame>
    <description>Safety of [18F]GE-226 injection measured by haematology change from baseline measurements.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunology change from baseline measurement</measure>
    <time_frame>0 hour, 48 hours</time_frame>
    <description>Safety of [18F]GE-226 injection measured by clinically significant changes from baseline measurements in immunology</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urine change from baseline measurement</measure>
    <time_frame>0 hour, 48 hours</time_frame>
    <description>Safety of [18F]GE-226 injection measured by clinically significant changes from baseline measurements in urine</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EEG change from baseline measurement</measure>
    <time_frame>0 hour, 48 hours</time_frame>
    <description>Safety of [18F]GE-226 injection measured by clinically significant changes from baseline measurements in ECG</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>HER2 positive metastatic breast cancer</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HER2 negative metastatic breast cancer</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>[18F]GE-226</intervention_name>
    <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.</description>
    <arm_group_label>HER2 negative metastatic breast cancer</arm_group_label>
    <arm_group_label>HER2 positive metastatic breast cancer</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Female patients with a histological diagnosis of breast cancer with known HER2 status&#xD;
             ((8 positive and 8 negative).&#xD;
&#xD;
          2. Written informed consent prior to admission in the study.&#xD;
&#xD;
          3. Target lesion diameter of ≥15mm that has not been previously irradiated.&#xD;
&#xD;
          4. Female patients aged ≥ 18 years of age.&#xD;
&#xD;
          5. For all patients: histologically confirmed locally advanced/metastatic breast cancer&#xD;
             with a biopsy within the last 12 months confirming HER2 status by either&#xD;
             immunohistochemistry (IHC), Silver In Situ Hybridization (SISH) or Fluorescent In Situ&#xD;
             Hybridization (FISH).&#xD;
&#xD;
          6. ECOG performance status 0-2&#xD;
&#xD;
          7. Negative urine pregnancy test (within 2 hours prior to injection of imaging agent) in&#xD;
             women of child bearing age and willingness to use contraception (barrier, abstinence,&#xD;
             non-hormonal) for 3 weeks after injection of [18F]GE-226&#xD;
&#xD;
          8. Life expectancy &gt; 3 months&#xD;
&#xD;
          9. Adequate organ function as defined by&#xD;
&#xD;
               -  Hb≥10g/L&#xD;
&#xD;
               -  WBC≥3.0 x 109/L&#xD;
&#xD;
               -  PLT≥80 x 109/L&#xD;
&#xD;
               -  Serum creatinine ≤1.4mg/dl&#xD;
&#xD;
               -  SGOT and SGPT ≤2 x ULN&#xD;
&#xD;
               -  Total bilirubin ≤ 2 x ULN or 3.0 mg/dl in patients with Gilbert's syndrome&#xD;
&#xD;
         10. Patients must have been appropriately staged using FDG-PET within 42 days of study&#xD;
             entry and additional imaging according to local standard of care&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant or lactating women.&#xD;
&#xD;
          2. History of cardiac disease (myocardial infarction, arrhythmias requiring therapy,&#xD;
             symptomatic valvular disease, cardiomyopathy, or pericarditis).&#xD;
&#xD;
          3. Evidence of significant medical condition or laboratory finding which, in the opinion&#xD;
             of the Investigator, makes it undesirable for the patient to participate in the trial.&#xD;
&#xD;
          4. Participants with severe claustrophobia or who are unable to lie flat or fit into the&#xD;
             scanner (≥350 lbs (160 Kg)).&#xD;
&#xD;
          5. Prior use within 14 days of enrolment or concurrent therapy with any other&#xD;
             investigational agent.&#xD;
&#xD;
          6. Patients classified as radiation workers&#xD;
&#xD;
          7. Patients on therapeutic doses of anticoagulants, or with a raised prothrombin time&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Female patients with a histological diagnosis of breast cancer with known HER2 status ((8 positive and 8 negative).</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Laura M Kenny, MD FRCP PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Imperial College London</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>HERPET Trial Coordinator</last_name>
    <phone>0207 59 42804</phone>
    <email>herpet@imperial.ac.uk; g.gopalakrishnan@imperial.ac.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Gosala Gopalakrishnan, PhD</last_name>
    <phone>0207 59 42804</phone>
    <email>g.gopalakrishnan@imperial.ac.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Imperial College Healthcare NHS Trust</name>
      <address>
        <city>London</city>
        <zip>W12 0NN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gosala Gopalakrishnan, PhD</last_name>
      <phone>0207 59 42804</phone>
      <email>g.gopalakrishnan@imperial.ac.uk</email>
    </contact>
    <investigator>
      <last_name>Laura M Kenny, MBBS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <last_update_submitted>January 3, 2023</last_update_submitted>
  <last_update_submitted_qc>January 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 4, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HER2</keyword>
  <keyword>imaging</keyword>
  <keyword>PET</keyword>
  <keyword>positron emission tomography</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03827317
org study id: 2015-004027-31
nct id: NCT03827317
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Non-randomised cohort
primary purpose: Other
masking: None (Open Label)
measure: Tumoral uptake of [18F]GE-226 in patients with breast cancer measured using semi-quantitative parameters
time frame: 24 months
description: Tumoral uptake of [18F]GE-226 in patients with HER2 positive and HER2 negative breast cancer measured using SUV and AUC.
measure: Tumoral uptake of [18F]GE-226 in patients with breast cancer measured using fully quantitative parameters
time frame: 24 months
description: 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.
measure: Adverse events of [18F]GE-226 injection
time frame: 0 hour, 48 hours
description: Safety of [18F]GE-226 measured by adverse events from administration of [18F]GE-226 injection throughout the study period.
measure: Serum biochemistry change from baseline measurement
time frame: 0 hour, 48 hours
description: Safety of [18F]GE-226 injection measured by clinically significant changes from baseline measurements in serum biochemistry finding.
measure: Haematology change from baseline measurement
time frame: 0 hour, 48 hours
description: Safety of [18F]GE-226 injection measured by haematology change from baseline measurements.
measure: Immunology change from baseline measurement
time frame: 0 hour, 48 hours
description: Safety of [18F]GE-226 injection measured by clinically significant changes from baseline measurements in immunology
measure: Urine change from baseline measurement
time frame: 0 hour, 48 hours
description: Safety of [18F]GE-226 injection measured by clinically significant changes from baseline measurements in urine
measure: EEG change from baseline measurement
time frame: 0 hour, 48 hours
description: Safety of [18F]GE-226 injection measured by clinically significant changes from baseline measurements in ECG
arm group label: HER2 positive metastatic breast cancer
arm group type: Other
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.
arm group label: HER2 negative metastatic breast cancer
arm group type: Other
description: 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.
intervention type: Radiation
intervention name: [18F]GE-226
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.
arm group label: HER2 negative metastatic breast cancer
arm group label: HER2 positive metastatic breast cancer
criteria: 
gender: Female
gender based: Yes
gender description: Female patients with a histological diagnosis of breast cancer with known HER2 status ((8 positive and 8 negative).
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Laura M Kenny, MD FRCP PhD
role: Principal Investigator
affiliation: Imperial College London
last name: HERPET Trial Coordinator
phone: 0207 59 42804
email: herpet@imperial.ac.uk; g.gopalakrishnan@imperial.ac.uk
last name: Gosala Gopalakrishnan, PhD
phone: 0207 59 42804
email: g.gopalakrishnan@imperial.ac.uk
facility: 
status: Recruiting
contact: 
investigator: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Breast Neoplasms
sharing ipd: No