<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/NCT03282461</url>
  </required_header>
  <id_info>
    <org_study_id>D17064</org_study_id>
    <nct_id>NCT03282461</nct_id>
  </id_info>
  <brief_title>A Microdose Evaluation Study of ABY-029 in Head and Neck Oncology Surgery</brief_title>
  <official_title>A Phase 0 Open Label, Single-center Clinical Trial of ABY-029, an Anti-EGFR Fluorescence Imaging Agent Via Single Intravenous Injection to Subjects With Operable Head and Neck Cancer.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dartmouth-Hitchcock Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Dartmouth College</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Dartmouth-Hitchcock Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary study objective is to determine if microdoses of ABY-029 (up to 6X) lead to&#xD;
      detectable signals (defined as signal-to-noise ratio, SNR ≥10, with wide-field iFI) in&#xD;
      sampled tissues with an EGFR (epidermal growth factor receptor) pathology score ≥ 1 based on&#xD;
      histological staining.&#xD;
&#xD;
      The secondary study objective is to assess ex vivo the specificity of tumor binding in&#xD;
      resected specimens by measuring the corresponding molecular uptake and concentrations using&#xD;
      histopathology.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators plan to enroll a minimum of 6 and a maximum of 12 adult patients with a&#xD;
      diagnosis of operable head and neck cancer in this open label, single center, clinical trial&#xD;
      of ABY-029.&#xD;
&#xD;
      Administration of ABY-029 will occur as a single intravenous injection to subjects with&#xD;
      operable head and neck cancer approximately 1-3 hours prior to surgery.&#xD;
&#xD;
      Documentation of the tumor with digital photography will be performed at several time points&#xD;
      during surgery: pre-resection, at intermediate time points during surgery, and&#xD;
      post-resection. White light assessment of the tumor and boundaries will be performed by the&#xD;
      surgeon.&#xD;
&#xD;
      Intraoperative optical probe measurements will occur in areas of visible tumor as well as&#xD;
      normal appearing tissue. At multiple time points during each surgery and at the discretion of&#xD;
      the surgeon, optical probe measurements will be completed with the probe followed by biopsy&#xD;
      sampling of the same sites when they are intended for resection. Commonly, these acquisitions&#xD;
      will occur at first exposure of the tumor, at the approximate mid-point of tumor resection&#xD;
      (when a significant amount of tumor tissue is present in the operative field), at a point&#xD;
      nearing but prior to completion of tumor resection (when a small amount of tumor tissue is&#xD;
      presumably present), and at the intended completion of tumor resection (when residual tumor&#xD;
      may or may not exist). At a data collection time point, optical probe measurements will be&#xD;
      performed and archived for analysis and locations may be biopsied when tissue is intended for&#xD;
      resection.&#xD;
&#xD;
      Any normal tissue removed as part of surgical procedure will be sampled. Samples may be taken&#xD;
      from tissue outside the &quot;antic&quot; tumor volume but resected as part of the procedure along the&#xD;
      surgical corridor. All tissue collected will be submitted to pathology for routine&#xD;
      processing.&#xD;
&#xD;
      After tissue is removed breadloafed sections will be placed on a fluorescence scanning imager&#xD;
      for complete measurement of signal on the exposed surfaces. Pathological analysis for EGFR&#xD;
      status will be completed at selected regions around the faces of each breadloaf section.&#xD;
&#xD;
      The protocol is not a safety study since no physiological effects are expected at microdose&#xD;
      levels of ABY-029. Rather, doses have been selected to determine if a fluorescence signal can&#xD;
      be detected by wide-field imaging technology with a signal-to-noise ratio of 10, which is&#xD;
      considered necessary for subsequent assessment of diagnostic performance of ABY-029 as a&#xD;
      tumor biomarker sufficient to guide surgical resection in the future. No diagnostic or&#xD;
      therapeutic intent is proposed, and study drug administration is not intended to alter the&#xD;
      extent of planned tumor resection during the surgical procedure.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 24, 2018</start_date>
  <completion_date type="Actual">December 18, 2020</completion_date>
  <primary_completion_date type="Actual">December 18, 2020</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>open label</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>none - open label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Signal detection</measure>
    <time_frame>Day of surgery, up to 1 week after surgery</time_frame>
    <description>For each pathology, predictive models of the odds of tumor positivity for biopsies given concentration of ABY-029 will be constructed. Histologically confirmed tumor status from biopsies will be statistically analyzed against the predictive models. The quantitative fluorescence measures will also be assessed for their fit with statistics. The predictive accuracy of the model fit will be summarized through an index.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlation of spatial patterns of EGFR expression</measure>
    <time_frame>within 1 week of surgery</time_frame>
    <description>Regions within the wide-field FI images will be classified as tumor on the basis of their fluorescence signals. Continuous, quantitative optical response data will also be available from the intraoperative probe recordings within the fields-of-view. Two-way classification tables will be examined for agreement between the methods for the &quot;tumor&quot; and &quot;not tumor&quot; categories from an individual patient. Statistical analysis will be used to determine if there is agreement with the region classifications.&#xD;
In a second analysis, histopathology from biopsies taken at FI-positive and negative sites will be classified as non-tumor tissue, solid tumor, infiltrating tumor, or indeterminate. The positive predictive values of these locations within the wide-field images will be calculated for each individual. These data will also be analyzed for sensitivity and specificity of the fluorescence image signatures relative to the reference standard (histopathology).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Head and Neck Cancer</condition>
  <arm_group>
    <arm_group_label>ABY-029</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Between 3-9 patients will be administered ABY-029 as a single intravenous injection approximately 1-3 hours prior to surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ABY-029</intervention_name>
    <description>A sample size of 6-12 patients in this open label, single center, clinical trial of ABY-029. Administration will occur as a single intravenous injection to subjects with operable head and neck cancer approximately 1-3 hours prior to surgery.</description>
    <arm_group_label>ABY-029</arm_group_label>
    <other_name>ABY-029 trifluoroacetate salt</other_name>
    <other_name>IRDye® 800CW Maleimide labeled Affibody peptide</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Preoperative diagnosis of head and neck cancer.&#xD;
&#xD;
          2. Tumor judged to be operable based on preoperative imaging studies.&#xD;
&#xD;
          3. Valid informed consent by subject or subject's Legally Authorized Representative.&#xD;
&#xD;
          4. Age ≥ 18 years old.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant women or women who are breast feeding.&#xD;
&#xD;
          2. Patients on any experimental anti-EGFR targeted therapies, either investigational or&#xD;
             FDA approved.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joseph A Paydarfar, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dartmouth-Hitchcock Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dartmouth-Hitchcock Medical Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 14, 2017</study_first_posted>
  <last_update_submitted>May 17, 2023</last_update_submitted>
  <last_update_submitted_qc>May 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dartmouth-Hitchcock Medical Center</investigator_affiliation>
    <investigator_full_name>Joseph A. Paydarfar</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Head and Neck Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 21, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/61/NCT03282461/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03282461
org study id: D17064
nct id: NCT03282461
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The primary study objective is to determine if microdoses of ABY-029 (up to 6X) lead to
      detectable signals (defined as signal-to-noise ratio, SNR ≥10, with wide-field iFI) in
      sampled tissues with an EGFR (epidermal growth factor receptor) pathology score ≥ 1 based on
      histological staining.

      The secondary study objective is to assess ex vivo the specificity of tumor binding in
      resected specimens by measuring the corresponding molecular uptake and concentrations using
      histopathology.
The investigators plan to enroll a minimum of 6 and a maximum of 12 adult patients with a
      diagnosis of operable head and neck cancer in this open label, single center, clinical trial
      of ABY-029.

      Administration of ABY-029 will occur as a single intravenous injection to subjects with
      operable head and neck cancer approximately 1-3 hours prior to surgery.

      Documentation of the tumor with digital photography will be performed at several time points
      during surgery: pre-resection, at intermediate time points during surgery, and
      post-resection. White light assessment of the tumor and boundaries will be performed by the
      surgeon.

      Intraoperative optical probe measurements will occur in areas of visible tumor as well as
      normal appearing tissue. At multiple time points during each surgery and at the discretion of
      the surgeon, optical probe measurements will be completed with the probe followed by biopsy
      sampling of the same sites when they are intended for resection. Commonly, these acquisitions
      will occur at first exposure of the tumor, at the approximate mid-point of tumor resection
      (when a significant amount of tumor tissue is present in the operative field), at a point
      nearing but prior to completion of tumor resection (when a small amount of tumor tissue is
      presumably present), and at the intended completion of tumor resection (when residual tumor
      may or may not exist). At a data collection time point, optical probe measurements will be
      performed and archived for analysis and locations may be biopsied when tissue is intended for
      resection.

      Any normal tissue removed as part of surgical procedure will be sampled. Samples may be taken
      from tissue outside the "antic" tumor volume but resected as part of the procedure along the
      surgical corridor. All tissue collected will be submitted to pathology for routine
      processing.

      After tissue is removed breadloafed sections will be placed on a fluorescence scanning imager
      for complete measurement of signal on the exposed surfaces. Pathological analysis for EGFR
      status will be completed at selected regions around the faces of each breadloaf section.

      The protocol is not a safety study since no physiological effects are expected at microdose
      levels of ABY-029. Rather, doses have been selected to determine if a fluorescence signal can
      be detected by wide-field imaging technology with a signal-to-noise ratio of 10, which is
      considered necessary for subsequent assessment of diagnostic performance of ABY-029 as a
      tumor biomarker sufficient to guide surgical resection in the future. No diagnostic or
      therapeutic intent is proposed, and study drug administration is not intended to alter the
      extent of planned tumor resection during the surgical procedure.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: open label
primary purpose: Treatment
masking: None (Open Label)
masking description: none - open label
measure: Signal detection
time frame: Day of surgery, up to 1 week after surgery
description: For each pathology, predictive models of the odds of tumor positivity for biopsies given concentration of ABY-029 will be constructed. Histologically confirmed tumor status from biopsies will be statistically analyzed against the predictive models. The quantitative fluorescence measures will also be assessed for their fit with statistics. The predictive accuracy of the model fit will be summarized through an index.
measure: Correlation of spatial patterns of EGFR expression
time frame: within 1 week of surgery
description: Regions within the wide-field FI images will be classified as tumor on the basis of their fluorescence signals. Continuous, quantitative optical response data will also be available from the intraoperative probe recordings within the fields-of-view. Two-way classification tables will be examined for agreement between the methods for the "tumor" and "not tumor" categories from an individual patient. Statistical analysis will be used to determine if there is agreement with the region classifications.
In a second analysis, histopathology from biopsies taken at FI-positive and negative sites will be classified as non-tumor tissue, solid tumor, infiltrating tumor, or indeterminate. The positive predictive values of these locations within the wide-field images will be calculated for each individual. These data will also be analyzed for sensitivity and specificity of the fluorescence image signatures relative to the reference standard (histopathology).
arm group label: ABY-029
arm group type: Experimental
description: Between 3-9 patients will be administered ABY-029 as a single intravenous injection approximately 1-3 hours prior to surgery.
intervention type: Drug
intervention name: ABY-029
description: A sample size of 6-12 patients in this open label, single center, clinical trial of ABY-029. Administration will occur as a single intravenous injection to subjects with operable head and neck cancer approximately 1-3 hours prior to surgery.
arm group label: ABY-029
other name: ABY-029 trifluoroacetate salt
other name: IRDye® 800CW Maleimide labeled Affibody peptide
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Joseph A Paydarfar, MD
role: Principal Investigator
affiliation: Dartmouth-Hitchcock Medical Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Dartmouth-Hitchcock Medical Center
investigator full name: Joseph A. Paydarfar
investigator title: Principal Investigator
mesh term: Head and Neck Neoplasms
sharing ipd: No
provided document: 