<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/NCT03830996</url>
  </required_header>
  <id_info>
    <org_study_id>WeeklyEBV</org_study_id>
    <nct_id>NCT03830996</nct_id>
  </id_info>
  <brief_title>Weekly Plasma EBV DNA for Non-metastatic Nasopharyngeal Carcinoma</brief_title>
  <official_title>Weekly Plasma EBV DNA for Non-metastatic Nasopharyngeal Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The University of Hong Kong</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>
      Nasopharyngeal carcinoma (NPC) is an endemic malignancy in Southern China, Hong Kong, Taiwan,&#xD;
      Singapore and Malaysia. It is highly associated with Epstein-Barr virus (EBV). Radiation&#xD;
      therapy alone is indicated for early stage I to II diseases while concurrent chemoradiation&#xD;
      is required for more advanced stage III to IVB diseases. Intensity-modulated radiation&#xD;
      therapy (IMRT) is the standard radiation technique for NPC, in virtue of its superior target&#xD;
      coverage and dose sparing to adjacent critical organs-at-risks.&#xD;
&#xD;
      Plasma EBV DNA and other novel plasma biomarkers have been extensively investigated in NPC.&#xD;
      Previous studies have proven their predictive and prognostic values in NPC diagnosis,&#xD;
      surveillance and survival outcomes.&#xD;
&#xD;
      Investigators would like to investigate the roles of plasma biomarkers including plasma EBV&#xD;
      DNA on treatment response evaluation, survival and prognosis on NPC, in the modern era of&#xD;
      precision radiation therapy. This will help provide important information on refining on the&#xD;
      current edition of AJCC/UICC staging classification.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with histologically confirmed previously untreated NPC are be recruited to join tis&#xD;
      study. The study has obtained approval from local institutional review board.&#xD;
&#xD;
      After written informed consent, baseline investigations including blood tests for routine&#xD;
      hematology, biochemistry and plasma EBV DNA will be taken. Only 3ml of EDTA blood will be&#xD;
      taken for plasma EBV DNA and other potential biomarkers. Patients will also undergo baseline&#xD;
      imaging investigations including positron-emission tomography with integrated computed&#xD;
      tomography (PET-CT) and magnetic resonance imaging (MRI) of the head and neck regions. An&#xD;
      routine nasoendoscopy and nasopharyngeal biopsies will be obtained to confirm and delineate&#xD;
      the mucosal extent of the disease.&#xD;
&#xD;
      If confirmed non-metastatic, patients will be treated with IMRT using 7-9 radiation beams. A&#xD;
      total dose of 70Gy in 33-35 fractions over 6.5 to 7 weeks will be given. For advanced stage&#xD;
      III to IVB diseases, concurrent chemoradiation using cisplatin 100mg/m2 on Day 1, 22 and 43&#xD;
      of IMRT followed by 3 cycles of adjuvant chemotherapy with cisplatin 80mg/m2 on Day 1 and&#xD;
      5-FU 1000mg/m2 from Day 1 to Day 4 every 4 weeks for 3 more cycles starting 4 weeks after&#xD;
      completion of IMRT will also be given. Some patients will also receive induction chemotherapy&#xD;
      with cisplatin100mg/m2 on Day 1 and 5-FU 1000mg/m2 on Day 1 to 5, administered every 3 weeks&#xD;
      for 3 cycles before commencement of chemoradiation, at the discretion of treating oncologists&#xD;
      if the primary tumours are close to critical organs e.g. brainstem, optic chiasm or optic&#xD;
      nerves.&#xD;
&#xD;
      After treatment patients will undergo nasopharyngeal biopsies, patients will undergo&#xD;
      nasopharyngeal biopsies again at 8 weeks after completion of IMRT to confirm histological&#xD;
      complete local remission. Blood will be taken again on the same day for plasma EBV DNA and&#xD;
      other potential biomarkers. Additional biopsies and salvage local treatment e.g.&#xD;
      brachytherapy, stereotactic or IMRT boost will be offered to patients who have persistent&#xD;
      local disease at 12 weeks after completion of IMRT. If complete local remission is confirmed,&#xD;
      patient will have regular follow up every 3 to 4 months for surveillance and survival&#xD;
      outcomes. Regular imaging with MRI and CT scans every 3 to 4 months will also be arranged as&#xD;
      well. Plasma EBV DNA will be measured at weekly intervals until EBV DNA is undetectable.&#xD;
&#xD;
      For those with metastatic diseases, systemic chemotherapy (platinum-based chemotherapy) will&#xD;
      be offered. Blood taking for plasma EBV DNA and other potential biomarkers at baseline before&#xD;
      chemotherapy commencement and then after every 3 cycles will be arranged. Imaging&#xD;
      examinations with CT and MRI scans will be arranged at baseline and then after 3-4 cycles of&#xD;
      chemotherapy for tumour response evaluation.&#xD;
&#xD;
      The trend of baseline and serial plasma EBV DNA will be monitored prospectively.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 2016</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">December 2020</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>Progression-free survival</measure>
    <time_frame>3 years</time_frame>
    <description>Progression-free survival is calculated from the date of diagnosis of NPC to the date of progression of NPC or the date of death from any cause, whichever comes earlier.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>3 years</time_frame>
    <description>Overall survival is calculated from the date of diagnosis of NPC to the date of death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Distant metastasis-free survival</measure>
    <time_frame>3 years</time_frame>
    <description>Distant metastasis-free survival is calculated from the date of diagnosis of NPC to the date of distant metastasis or date of death from any cause, whichever comes earlier.</description>
  </secondary_outcome>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Nasopharyngeal Carcinoma</condition>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with histologically confirmed previously untreated nasopharyngeal carcinoma (NPC)&#xD;
        will be invited to join this study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with histologically confirmed previously untreated nasopharyngeal carcinoma&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who are pregnant or lactating&#xD;
&#xD;
          -  Patients who are not mentally capable of giving written informed consent&#xD;
&#xD;
          -  Patients with performance status ECOG=3 or above or patients who are expected not able&#xD;
             to tolerate radiation therapy and/or chemotherapy&#xD;
&#xD;
          -  Patients who refuse active treatment for their nasopharyngeal carcinoma&#xD;
&#xD;
          -  Patients who cannot comply with radiation therapy and/or chemotherapy for their&#xD;
             nasopharyngeal carcinoma&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Victor Lee, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of Hong Kong</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Victor Lee, MD</last_name>
    <phone>852-22554352</phone>
    <email>vhflee@hku.hk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Department of Clinical Oncology, Queen Mary Hospital</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Victor Lee, FRCR</last_name>
      <phone>852-2255-4352</phone>
      <email>vhflee@hku.hk</email>
    </contact>
    <contact_backup>
      <last_name>Ka-On Lam, FRCR</last_name>
      <phone>852-2255-4352</phone>
      <email>lamkaon@hku.hk</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Hong Kong</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>February 4, 2019</study_first_submitted>
  <study_first_submitted_qc>February 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 5, 2019</study_first_posted>
  <last_update_submitted>September 29, 2019</last_update_submitted>
  <last_update_submitted_qc>September 29, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 1, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The University of Hong Kong</investigator_affiliation>
    <investigator_full_name>Dr. Victor H.F. Lee</investigator_full_name>
    <investigator_title>Clinical Associate Professor</investigator_title>
  </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>
  <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/NCT03830996
org study id: WeeklyEBV
nct id: NCT03830996
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Nasopharyngeal carcinoma (NPC) is an endemic malignancy in Southern China, Hong Kong, Taiwan,
      Singapore and Malaysia. It is highly associated with Epstein-Barr virus (EBV). Radiation
      therapy alone is indicated for early stage I to II diseases while concurrent chemoradiation
      is required for more advanced stage III to IVB diseases. Intensity-modulated radiation
      therapy (IMRT) is the standard radiation technique for NPC, in virtue of its superior target
      coverage and dose sparing to adjacent critical organs-at-risks.

      Plasma EBV DNA and other novel plasma biomarkers have been extensively investigated in NPC.
      Previous studies have proven their predictive and prognostic values in NPC diagnosis,
      surveillance and survival outcomes.

      Investigators would like to investigate the roles of plasma biomarkers including plasma EBV
      DNA on treatment response evaluation, survival and prognosis on NPC, in the modern era of
      precision radiation therapy. This will help provide important information on refining on the
      current edition of AJCC/UICC staging classification.
Patients with histologically confirmed previously untreated NPC are be recruited to join tis
      study. The study has obtained approval from local institutional review board.

      After written informed consent, baseline investigations including blood tests for routine
      hematology, biochemistry and plasma EBV DNA will be taken. Only 3ml of EDTA blood will be
      taken for plasma EBV DNA and other potential biomarkers. Patients will also undergo baseline
      imaging investigations including positron-emission tomography with integrated computed
      tomography (PET-CT) and magnetic resonance imaging (MRI) of the head and neck regions. An
      routine nasoendoscopy and nasopharyngeal biopsies will be obtained to confirm and delineate
      the mucosal extent of the disease.

      If confirmed non-metastatic, patients will be treated with IMRT using 7-9 radiation beams. A
      total dose of 70Gy in 33-35 fractions over 6.5 to 7 weeks will be given. For advanced stage
      III to IVB diseases, concurrent chemoradiation using cisplatin 100mg/m2 on Day 1, 22 and 43
      of IMRT followed by 3 cycles of adjuvant chemotherapy with cisplatin 80mg/m2 on Day 1 and
      5-FU 1000mg/m2 from Day 1 to Day 4 every 4 weeks for 3 more cycles starting 4 weeks after
      completion of IMRT will also be given. Some patients will also receive induction chemotherapy
      with cisplatin100mg/m2 on Day 1 and 5-FU 1000mg/m2 on Day 1 to 5, administered every 3 weeks
      for 3 cycles before commencement of chemoradiation, at the discretion of treating oncologists
      if the primary tumours are close to critical organs e.g. brainstem, optic chiasm or optic
      nerves.

      After treatment patients will undergo nasopharyngeal biopsies, patients will undergo
      nasopharyngeal biopsies again at 8 weeks after completion of IMRT to confirm histological
      complete local remission. Blood will be taken again on the same day for plasma EBV DNA and
      other potential biomarkers. Additional biopsies and salvage local treatment e.g.
      brachytherapy, stereotactic or IMRT boost will be offered to patients who have persistent
      local disease at 12 weeks after completion of IMRT. If complete local remission is confirmed,
      patient will have regular follow up every 3 to 4 months for surveillance and survival
      outcomes. Regular imaging with MRI and CT scans every 3 to 4 months will also be arranged as
      well. Plasma EBV DNA will be measured at weekly intervals until EBV DNA is undetectable.

      For those with metastatic diseases, systemic chemotherapy (platinum-based chemotherapy) will
      be offered. Blood taking for plasma EBV DNA and other potential biomarkers at baseline before
      chemotherapy commencement and then after every 3 cycles will be arranged. Imaging
      examinations with CT and MRI scans will be arranged at baseline and then after 3-4 cycles of
      chemotherapy for tumour response evaluation.

      The trend of baseline and serial plasma EBV DNA will be monitored prospectively.
observational model: Cohort
time perspective: Prospective
measure: Progression-free survival
time frame: 3 years
description: Progression-free survival is calculated from the date of diagnosis of NPC to the date of progression of NPC or the date of death from any cause, whichever comes earlier.
measure: Overall survival
time frame: 3 years
description: Overall survival is calculated from the date of diagnosis of NPC to the date of death from any cause
measure: Distant metastasis-free survival
time frame: 3 years
description: Distant metastasis-free survival is calculated from the date of diagnosis of NPC to the date of distant metastasis or date of death from any cause, whichever comes earlier.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Victor Lee, MD
role: Principal Investigator
affiliation: The University of Hong Kong
last name: Victor Lee, MD
phone: 852-22554352
email: vhflee@hku.hk
facility: 
status: Recruiting
contact: 
contact backup: 
country: Hong Kong
responsible party type: Principal Investigator
investigator affiliation: The University of Hong Kong
investigator full name: Dr. Victor H.F. Lee
investigator title: Clinical Associate Professor
mesh term: Carcinoma
mesh term: Nasopharyngeal Carcinoma
sharing ipd: No