<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/NCT04417985</url>
  </required_header>
  <id_info>
    <org_study_id>NSC 100-2314-B-182A-053</org_study_id>
    <nct_id>NCT04417985</nct_id>
  </id_info>
  <brief_title>Prognostic Utility of the Imaging and Biological Signatures in Nasopharyngeal Carcinoma</brief_title>
  <official_title>Integrating Biomarkers From Serum/Plasma and Molecular Images to Predict Occult Distant Metastases in Nasopharyngeal Carcinoma Patients With M0 Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chang Gung Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chang Gung Memorial Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Nasopharyngeal carcinoma (NPC) differs from other head and neck malignancies terms of its&#xD;
      epidemiology, pathology, and treatment outcome. Although NPC is a radiosensitive tumor,&#xD;
      distant recurrence remains a clinical challenge. Therefore, the investigators conducted this&#xD;
      study to prospectively investigate the role of imaging and blood biomarkers in predicting the&#xD;
      prognosis of NPC patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Background:&#xD;
&#xD;
           Nasopharyngeal carcinoma (NPC) differs from other head and neck malignancies terms of&#xD;
           its epidemiology, pathology, and treatment outcome. NPC has a good local tumor control&#xD;
           rate but a higher incidence of distant metastasis compared with squamous cell carcinomas&#xD;
           of other regions of the head and neck. Thus, it's usually considered a distinct study&#xD;
           group.&#xD;
&#xD;
           A good prognostic model for the development of distant failure for NPC patients is still&#xD;
           lacking. It is well known that Epstein-Barr virus (EBV) genomes are present in almost&#xD;
           every NPC tumor cell, irrespective of histologic differentiation and geographic&#xD;
           distribution. Various EBV-derived/related factors, therefore, have been used as NPC&#xD;
           tumor markers, including EBV-specific viral capsid antigen (VCA) IgA and cell-free EBV&#xD;
           DNA. The measurement of cell-free EBV DNA load has already been shown to be a good&#xD;
           pretreatment prognostic indicator. Another important feature of NPC is that the tumors&#xD;
           are characterized by heavy infiltration of nonmalignant lymphocytes and might play an&#xD;
           important role in tumorigenesis; and cytokines and chemokines may represent the key&#xD;
           mediators of this interaction. Compelling evidence has also emerged in recent years&#xD;
           suggesting that cytokines and chemokines play important roles in regulating processes&#xD;
           critical to tumor progression, such as proliferation and metastasis.&#xD;
&#xD;
           Beyond blood biomarkers, standard uptake value (SUV) from FDG PET could predict&#xD;
           treatment failure in NPC patients. On the other hand, apparent diffusion coefficient&#xD;
           (ADC) from diffusion-weighted MRI (DWI) has been shown to be an important prognostic&#xD;
           marker in cancer patients, including head and neck cancer.&#xD;
&#xD;
        2. Aim:&#xD;
&#xD;
           To investigate the roles of imaging and blood biomarkers in predicting distant failures,&#xD;
           recurrences, and survival in NPC patients.&#xD;
&#xD;
        3. Study design:&#xD;
&#xD;
      Study participants:&#xD;
&#xD;
      Patients with a histological diagnosis of primary M0 NPC were deemed eligible. All study&#xD;
      participants received both 18F-FDG PET/CT and head-neck MRI imaging before treatment, during&#xD;
      radiotherapy, and 3 months after the definitive treatment. The blood sample was collected on&#xD;
      the same day of the PET/CT scan.&#xD;
&#xD;
      18F-FDG PET/CT: Study participants were instructed to fast for six hours before the PET&#xD;
      study. FDG (370-444 MBq) was administered intravenously. No intravenous contrast material was&#xD;
      administered for CT scans. The participants underwent head to mid-thigh scans. PET and CT&#xD;
      images were acquired consecutively 50 to 70 minutes after the injection of 18F-FDG. Before&#xD;
      PET acquisition, a standard helical CT scan was acquired from the head to the proximal thighs&#xD;
      using the manufacturer's dose reduction software. The PET images were reconstructed using the&#xD;
      CT data for attenuation correction and an ordered subsets expectation maximization iterative&#xD;
      reconstruction algorithm.&#xD;
&#xD;
      MRI :&#xD;
&#xD;
      MRI was performed at 3 Tesla (MAGNETOM® Trio with Tim; Siemens Medical Solutions, Bonn,&#xD;
      Germany). Dedicated MRI of the head and neck region was obtained in the axial projection with&#xD;
      T1-weighted turbo spin echo (TSE) sequence and subsequently with T2-weighted TSE sequences&#xD;
      with fat saturation. After intravenous administration of gadopentetate dimeglumine&#xD;
      (Magnevist; Schering, Berlin, Germany) at 3 mL/sec with a dose of 0.1 mmol/kg, MRI of the&#xD;
      head and neck region was performed using a fat-saturated T1-weighted TSE sequence in the&#xD;
      axial and coronal planes. DWI was acquired using single shot spin-echo echo-planar imaging&#xD;
      with a modified Stejskal-Tanner diffusion gradient pulsing scheme.&#xD;
&#xD;
      Collection and storage of blood plasma:&#xD;
&#xD;
      Ten-milliliter samples of peripheral blood were drawn from subjects using standardized&#xD;
      phlebotomy procedures and collected into an EDTA tube for isolation of plasma. Blood samples&#xD;
      were centrifuged at 2000×g. Plasma was immediately aliquoted, transferred into plain&#xD;
      polypropylene tubes, and was stored in a dedicated freezer at -80°C. No more than one&#xD;
      freeze-thaw cycle was allowed for each plasma sample.&#xD;
&#xD;
      Statistical analysis:&#xD;
&#xD;
      Recurrence-free survival (RFS) and overall survival (OS) served as main outcome measures. RFS&#xD;
      was defined as the time between the end of treatment and the date of recurrence (tumor&#xD;
      relapse or death) or censored at the date of the last follow-up. Distant failure-free&#xD;
      survival was also calculated from the date of diagnosis to the date of documented distant&#xD;
      recurrences, or censored at the last follow-up date. OS was calculated from the date of&#xD;
      diagnosis to the date of death or censor at the date of the last follow-up for surviving&#xD;
      study participants. The cutoff values for the clinical variables, blood biomarkers, and&#xD;
      imaging parameters in survival analysis were determined using the log-rank test based on the&#xD;
      RFS and OS rates observed in the entire study cohort. Survival curves were plotted using the&#xD;
      Kaplan-Meier method. The effect of each individual variable was initially evaluated using&#xD;
      univariate analysis. Cox regression models were used to identify the predictors of survival.&#xD;
      Two-tailed P values &lt; 0.05 were considered statistically significant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2011</start_date>
  <completion_date type="Actual">July 31, 2014</completion_date>
  <primary_completion_date type="Actual">July 31, 2014</primary_completion_date>
  <phase>N/A</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>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recurrence-free survival</measure>
    <time_frame>5 years</time_frame>
    <description>The time between the end of chemoradiotherapy and the date of recurrence or censored at the date of the last follow-up</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">112</enrollment>
  <condition>Nasopharyngeal Carcinoma</condition>
  <arm_group>
    <arm_group_label>18F-FDG PET/CT with MRI and blood sampling</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The enrolled subjects received 18F-FDG PET/CT and MRI before, during, and after the primary definitive treatment.&#xD;
The blood sample was collected on the same day of PET/CT scan.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>18F-FDG PET/CT, MRI</intervention_name>
    <arm_group_label>18F-FDG PET/CT with MRI and blood sampling</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Biopsy proved primary M0 nasopharyngeal carcinoma&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Woman with pregnancy or during lactation&#xD;
&#xD;
          -  A history of other malignancies or presence of recurrent tumors&#xD;
&#xD;
          -  A serum glucose level &gt; 200mg/dL before PET scan&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sheng-Chieh Chan</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chang Gung Memorial Hospital</affiliation>
  </overall_official>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>June 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>June 4, 2020</last_update_submitted>
  <last_update_submitted_qc>June 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Nasopharyngeal Carcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluorodeoxyglucose F18</mesh_term>
  </intervention_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/NCT04417985
org study id: NSC 100-2314-B-182A-053
nct id: NCT04417985
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Nasopharyngeal carcinoma (NPC) differs from other head and neck malignancies terms of its
      epidemiology, pathology, and treatment outcome. Although NPC is a radiosensitive tumor,
      distant recurrence remains a clinical challenge. Therefore, the investigators conducted this
      study to prospectively investigate the role of imaging and blood biomarkers in predicting the
      prognosis of NPC patients.
1. Background:

           Nasopharyngeal carcinoma (NPC) differs from other head and neck malignancies terms of
           its epidemiology, pathology, and treatment outcome. NPC has a good local tumor control
           rate but a higher incidence of distant metastasis compared with squamous cell carcinomas
           of other regions of the head and neck. Thus, it's usually considered a distinct study
           group.

           A good prognostic model for the development of distant failure for NPC patients is still
           lacking. It is well known that Epstein-Barr virus (EBV) genomes are present in almost
           every NPC tumor cell, irrespective of histologic differentiation and geographic
           distribution. Various EBV-derived/related factors, therefore, have been used as NPC
           tumor markers, including EBV-specific viral capsid antigen (VCA) IgA and cell-free EBV
           DNA. The measurement of cell-free EBV DNA load has already been shown to be a good
           pretreatment prognostic indicator. Another important feature of NPC is that the tumors
           are characterized by heavy infiltration of nonmalignant lymphocytes and might play an
           important role in tumorigenesis; and cytokines and chemokines may represent the key
           mediators of this interaction. Compelling evidence has also emerged in recent years
           suggesting that cytokines and chemokines play important roles in regulating processes
           critical to tumor progression, such as proliferation and metastasis.

           Beyond blood biomarkers, standard uptake value (SUV) from FDG PET could predict
           treatment failure in NPC patients. On the other hand, apparent diffusion coefficient
           (ADC) from diffusion-weighted MRI (DWI) has been shown to be an important prognostic
           marker in cancer patients, including head and neck cancer.

        2. Aim:

           To investigate the roles of imaging and blood biomarkers in predicting distant failures,
           recurrences, and survival in NPC patients.

        3. Study design:

      Study participants:

      Patients with a histological diagnosis of primary M0 NPC were deemed eligible. All study
      participants received both 18F-FDG PET/CT and head-neck MRI imaging before treatment, during
      radiotherapy, and 3 months after the definitive treatment. The blood sample was collected on
      the same day of the PET/CT scan.

      18F-FDG PET/CT: Study participants were instructed to fast for six hours before the PET
      study. FDG (370-444 MBq) was administered intravenously. No intravenous contrast material was
      administered for CT scans. The participants underwent head to mid-thigh scans. PET and CT
      images were acquired consecutively 50 to 70 minutes after the injection of 18F-FDG. Before
      PET acquisition, a standard helical CT scan was acquired from the head to the proximal thighs
      using the manufacturer's dose reduction software. The PET images were reconstructed using the
      CT data for attenuation correction and an ordered subsets expectation maximization iterative
      reconstruction algorithm.

      MRI :

      MRI was performed at 3 Tesla (MAGNETOM® Trio with Tim; Siemens Medical Solutions, Bonn,
      Germany). Dedicated MRI of the head and neck region was obtained in the axial projection with
      T1-weighted turbo spin echo (TSE) sequence and subsequently with T2-weighted TSE sequences
      with fat saturation. After intravenous administration of gadopentetate dimeglumine
      (Magnevist; Schering, Berlin, Germany) at 3 mL/sec with a dose of 0.1 mmol/kg, MRI of the
      head and neck region was performed using a fat-saturated T1-weighted TSE sequence in the
      axial and coronal planes. DWI was acquired using single shot spin-echo echo-planar imaging
      with a modified Stejskal-Tanner diffusion gradient pulsing scheme.

      Collection and storage of blood plasma:

      Ten-milliliter samples of peripheral blood were drawn from subjects using standardized
      phlebotomy procedures and collected into an EDTA tube for isolation of plasma. Blood samples
      were centrifuged at 2000×g. Plasma was immediately aliquoted, transferred into plain
      polypropylene tubes, and was stored in a dedicated freezer at -80°C. No more than one
      freeze-thaw cycle was allowed for each plasma sample.

      Statistical analysis:

      Recurrence-free survival (RFS) and overall survival (OS) served as main outcome measures. RFS
      was defined as the time between the end of treatment and the date of recurrence (tumor
      relapse or death) or censored at the date of the last follow-up. Distant failure-free
      survival was also calculated from the date of diagnosis to the date of documented distant
      recurrences, or censored at the last follow-up date. OS was calculated from the date of
      diagnosis to the date of death or censor at the date of the last follow-up for surviving
      study participants. The cutoff values for the clinical variables, blood biomarkers, and
      imaging parameters in survival analysis were determined using the log-rank test based on the
      RFS and OS rates observed in the entire study cohort. Survival curves were plotted using the
      Kaplan-Meier method. The effect of each individual variable was initially evaluated using
      univariate analysis. Cox regression models were used to identify the predictors of survival.
      Two-tailed P values < 0.05 were considered statistically significant.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Recurrence-free survival
time frame: 5 years
description: The time between the end of chemoradiotherapy and the date of recurrence or censored at the date of the last follow-up
arm group label: 18F-FDG PET/CT with MRI and blood sampling
arm group type: Experimental
description: The enrolled subjects received 18F-FDG PET/CT and MRI before, during, and after the primary definitive treatment.
The blood sample was collected on the same day of PET/CT scan.
intervention type: Device
intervention name: 18F-FDG PET/CT, MRI
arm group label: 18F-FDG PET/CT with MRI and blood sampling
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Sheng-Chieh Chan
role: Principal Investigator
affiliation: Chang Gung Memorial Hospital
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Nasopharyngeal Carcinoma
mesh term: Fluorodeoxyglucose F18
sharing ipd: No