<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/NCT04428515</url>
  </required_header>
  <id_info>
    <org_study_id>135-2018</org_study_id>
    <nct_id>NCT04428515</nct_id>
  </id_info>
  <brief_title>Pilot Study to Evaluate Photoacoustic Imaging in Head and Neck Cancer</brief_title>
  <official_title>Pilot Study to Evaluate Photoacoustic Imaging in Head and Neck Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sunnybrook Health Sciences Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sunnybrook Health Sciences Centre</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>
      In this study, PA imaging will be used to examine the physiological and physical changes in&#xD;
      lymph node involvements of head and neck cancer during radiotherapy with or without&#xD;
      chemotherapy. Our objective in this pilot study will be to evaluate if PA parameters change&#xD;
      within the lymph node involvements during chemoradiation therapy over time. Our hope is to&#xD;
      use this information to correlate the changes in measured PA parameters with radiological&#xD;
      response.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A trained clinical research coordinator will evaluate and authorize that each screened&#xD;
      volunteer is a suitable subject for the study prior to enrolment. Written informed consent&#xD;
      will be obtained from each participant prior to any clinical research scans to be performed&#xD;
      on the subject. Those subjects who qualify will have their lymph node imaged using a PA&#xD;
      imaging system. Up to 50 subjects will be recruited for this study.&#xD;
&#xD;
      Participants will be imaged 5 times over the course of radiotherapy regimen, which span up to&#xD;
      7 weeks. The patients will be assessed with MRI 10 to 12 weeks after the completion of&#xD;
      Chemoradiation therapy as per the institution's standard of care. The lymph nodes will be&#xD;
      measured by a staff radiologist, and the sizing information will be used to categorize&#xD;
      patients into responders or non-responders. This information will be accessed using the&#xD;
      patient's electronic medical record. Each patient will be assigned an anonymized accession&#xD;
      number to the study that withholds any identifiers. There will be a complete accounting of&#xD;
      all missing and excluded data, if any.&#xD;
&#xD;
      Although we do not anticipate any adverse events, all AEs will be documented in the CRF, and&#xD;
      will be immediately reported to the REB, the overseeing physician responsible for the&#xD;
      patient's care, and the study principal investigators.&#xD;
&#xD;
      Descriptive statistics (arithmetic mean, standard deviation, and coefficient of variation)&#xD;
      and tabulation (stem and leaf plots) of study endpoints (absolute values and absolute&#xD;
      value/comparator differences) will be used. PA datasets will be tested for normality, using a&#xD;
      Shapiro-Wilk test (alpha=0.05). Comparative tests will use an independent t-test (or Mann&#xD;
      Whitney test for normality violations) to compare the PA measurements between different&#xD;
      breast masses (fibroadenomas, cysts, tumors).&#xD;
&#xD;
      In determining chemoradiation therapy evaluation, the primary endpoint, multiple linear&#xD;
      regression models to relate study endpoints to subject characteristics and a logistic&#xD;
      regression model will be used to build for multiparametric analysis of multiple PA parameters&#xD;
      as a predictive model to pathological response. Descriptive statistics (frequency per scan,&#xD;
      frequency per subject) and tabulation will be used to analyze the frequency of system&#xD;
      malfunction.&#xD;
&#xD;
      Overall Survival Evaluation, the secondary endpoint, will use linear discriminant analysis to&#xD;
      test for sensitivity, specificity and accuracy of the PA parameters as a diagnostic test.&#xD;
      Receiver-operating characteristic will be used to test for PA cutoff values and a logistic&#xD;
      regression model will be used to build for multiparametric analysis of multiple PA parameters&#xD;
      as a predictive model to pathological response.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 23, 2019</start_date>
  <completion_date type="Anticipated">April 23, 2024</completion_date>
  <primary_completion_date type="Anticipated">April 23, 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Correlation of response to treatment between photoacoustic parameters and final radiological outcome. measures of outcome.</measure>
    <time_frame>3 months</time_frame>
    <description>The primary study endpoint will investigate changes of measured PA markers and compare these to radiological assessment of response of lymph node involvement to chemoradiation therapy for head and neck cancer. Changes in PA parameters will be made to a pre-treatment point over the course of treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlation between photoacoustic parameters and five-year overall survival.</measure>
    <time_frame>5 years</time_frame>
    <description>The secondary study endpoint will correlate changes of measured PA markers to five-year overall survival (OS) of the same patient cohort. The survival status and of the patient cohort will be tracked after the treatment for five years based on the patient information system and follow up surveys if necessary.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Head and Neck Cancer</condition>
  <arm_group>
    <arm_group_label>Radiotherapy Response Monitoring</arm_group_label>
    <description>Those undergoing radiation therapy treatment to their lymph nodes upon diagnosis of head and neck cancer</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Men or women with confirmed head and neck carcinoma and will be treated with radiotherapy.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed head and neck carcinoma which has not been&#xD;
             treated with any first-line therapy and will be treated with radiotherapy&#xD;
&#xD;
          -  Measurable disease by ultrasound, or MRI performed within 28 days prior to treatment&#xD;
&#xD;
          -  Eastern Co-operative Oncology Group (ECOG) Performance Status of 0 or 1&#xD;
&#xD;
          -  Life expectancy of at least 6 months&#xD;
&#xD;
          -  Adequate bone marrow, liver and renal function as assessed by the following laboratory&#xD;
             requirements to be conducted within 7 days prior to dosing:&#xD;
&#xD;
               1. hemoglobin &gt;90 mg/dL&#xD;
&#xD;
               2. leukocytes &gt;3,000/mL&#xD;
&#xD;
               3. absolute neutrophil count &gt;1,500/mL&#xD;
&#xD;
               4. platelets &gt;100,000/mL&#xD;
&#xD;
               5. total bilirubin within normal institutional limits&#xD;
&#xD;
               6. AST(SGOT)/ALT(SGPT) &lt;2.5 X institutional upper limit of normal&#xD;
&#xD;
               7. creatinine within normal institutional limits or creatinine clearance &gt;60&#xD;
                  mL/min/1.73 m2 for patients with creatinine levels above institutional upper&#xD;
                  limit of normal&#xD;
&#xD;
          -  Subjects must give appropriate written informed consent prior to participation in the&#xD;
             study;&#xD;
&#xD;
          -  Subjects must be able and willing to comply with the safety procedures during the&#xD;
             Scanning Period;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chemotherapy, radiotherapy, or major surgery within 4 weeks prior to registering the&#xD;
             study or those who have not recovered from adverse events due to agents administered&#xD;
             more than 4 weeks prior to registration&#xD;
&#xD;
          -  Receiving any other investigational agents&#xD;
&#xD;
          -  Known brain metastases&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition&#xD;
&#xD;
          -  Contraindications to radiotherapy such as but not limited to:&#xD;
&#xD;
               1. previous radiotherapy to an involved area&#xD;
&#xD;
               2. active collagen vascular disease&#xD;
&#xD;
               3. genetic diseases associated with hyper-radiosensitivity&#xD;
&#xD;
          -  Any clinically serious infections requiring systemic anti-bacterial, antifungal or&#xD;
             antiviral therapy&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active&#xD;
             infection,&#xD;
&#xD;
          -  Symptomatic congestive heart failure, unstable angina pectoris, and cardiac arrhythmia&#xD;
&#xD;
          -  History of active ongoing seizure disorder&#xD;
&#xD;
          -  Any condition that is unstable or could jeopardize the safety of the patient and their&#xD;
             compliance in the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Gregory J Czarnota, PhD, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sunnybrook Health Sciences Centre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sunnybrook Health Sciences Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gregory J Czarnota, PhD, MD</last_name>
      <phone>(416)480-6128</phone>
      <email>gregory.czarnota@sunnybrook.ca</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>June 9, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>September 27, 2022</last_update_submitted>
  <last_update_submitted_qc>September 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sunnybrook Health Sciences Centre</investigator_affiliation>
    <investigator_full_name>Dr. Gregory Czarnota</investigator_full_name>
    <investigator_title>Senior Scientist</investigator_title>
  </responsible_party>
  <keyword>Photoacoustic</keyword>
  <keyword>Head and Neck</keyword>
  <keyword>Radiotherapy</keyword>
  <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>
  <!-- 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/NCT04428515
org study id: 135-2018
nct id: NCT04428515
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In this study, PA imaging will be used to examine the physiological and physical changes in
      lymph node involvements of head and neck cancer during radiotherapy with or without
      chemotherapy. Our objective in this pilot study will be to evaluate if PA parameters change
      within the lymph node involvements during chemoradiation therapy over time. Our hope is to
      use this information to correlate the changes in measured PA parameters with radiological
      response.
A trained clinical research coordinator will evaluate and authorize that each screened
      volunteer is a suitable subject for the study prior to enrolment. Written informed consent
      will be obtained from each participant prior to any clinical research scans to be performed
      on the subject. Those subjects who qualify will have their lymph node imaged using a PA
      imaging system. Up to 50 subjects will be recruited for this study.

      Participants will be imaged 5 times over the course of radiotherapy regimen, which span up to
      7 weeks. The patients will be assessed with MRI 10 to 12 weeks after the completion of
      Chemoradiation therapy as per the institution's standard of care. The lymph nodes will be
      measured by a staff radiologist, and the sizing information will be used to categorize
      patients into responders or non-responders. This information will be accessed using the
      patient's electronic medical record. Each patient will be assigned an anonymized accession
      number to the study that withholds any identifiers. There will be a complete accounting of
      all missing and excluded data, if any.

      Although we do not anticipate any adverse events, all AEs will be documented in the CRF, and
      will be immediately reported to the REB, the overseeing physician responsible for the
      patient's care, and the study principal investigators.

      Descriptive statistics (arithmetic mean, standard deviation, and coefficient of variation)
      and tabulation (stem and leaf plots) of study endpoints (absolute values and absolute
      value/comparator differences) will be used. PA datasets will be tested for normality, using a
      Shapiro-Wilk test (alpha=0.05). Comparative tests will use an independent t-test (or Mann
      Whitney test for normality violations) to compare the PA measurements between different
      breast masses (fibroadenomas, cysts, tumors).

      In determining chemoradiation therapy evaluation, the primary endpoint, multiple linear
      regression models to relate study endpoints to subject characteristics and a logistic
      regression model will be used to build for multiparametric analysis of multiple PA parameters
      as a predictive model to pathological response. Descriptive statistics (frequency per scan,
      frequency per subject) and tabulation will be used to analyze the frequency of system
      malfunction.

      Overall Survival Evaluation, the secondary endpoint, will use linear discriminant analysis to
      test for sensitivity, specificity and accuracy of the PA parameters as a diagnostic test.
      Receiver-operating characteristic will be used to test for PA cutoff values and a logistic
      regression model will be used to build for multiparametric analysis of multiple PA parameters
      as a predictive model to pathological response.
observational model: Cohort
time perspective: Prospective
measure: Correlation of response to treatment between photoacoustic parameters and final radiological outcome. measures of outcome.
time frame: 3 months
description: The primary study endpoint will investigate changes of measured PA markers and compare these to radiological assessment of response of lymph node involvement to chemoradiation therapy for head and neck cancer. Changes in PA parameters will be made to a pre-treatment point over the course of treatment.
measure: Correlation between photoacoustic parameters and five-year overall survival.
time frame: 5 years
description: The secondary study endpoint will correlate changes of measured PA markers to five-year overall survival (OS) of the same patient cohort. The survival status and of the patient cohort will be tracked after the treatment for five years based on the patient information system and follow up surveys if necessary.
arm group label: Radiotherapy Response Monitoring
description: Those undergoing radiation therapy treatment to their lymph nodes upon diagnosis of head and neck cancer
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
last name: Gregory J Czarnota, PhD, MD
role: Principal Investigator
affiliation: Sunnybrook Health Sciences Centre
facility: 
status: Recruiting
contact: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Sunnybrook Health Sciences Centre
investigator full name: Dr. Gregory Czarnota
investigator title: Senior Scientist
mesh term: Head and Neck Neoplasms
sharing ipd: No