<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/NCT03783871</url>
  </required_header>
  <id_info>
    <org_study_id>NEU_2017_07</org_study_id>
    <nct_id>NCT03783871</nct_id>
  </id_info>
  <brief_title>NeuWave HCC China Study</brief_title>
  <acronym>NW</acronym>
  <official_title>A Single-Arm, Prospective, Multicenter Study to Evaluate the Safety and Effectiveness of the NeuWave Certus Microwave Ablation System in Chinese Patients With Hepatocellular Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ethicon, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ethicon, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single-arm, prospective, multicenter, study. Individuals who are assessed for&#xD;
      microwave (MW) ablation of HCC in accordance with their institution's standard of care (SOC),&#xD;
      who meet study entry criteria and sign the informed consent, will be enrolled. The patients&#xD;
      will be treated with MW ablation and afterwards followed for up to 36 months after the&#xD;
      original ablation procedure to assess efficacy and safety. In addition to the final analysis&#xD;
      after all enrolled patients complete the 36-month observation period, a summary of selected&#xD;
      endpoints will be provided after all enrolled patients have completed each of the 1-month and&#xD;
      12-month visits.&#xD;
&#xD;
      To provide sites with an opportunity to get equal experience in the use of the Certus system,&#xD;
      there will 3 patients treated as part of a run-in phase. These patients will only be included&#xD;
      in the safety set.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients who have a single HCC tumor up to 5 cm or a maximum of 3 HCC tumors of up to 3 cm&#xD;
      per tumor will receive the same procedure: microwave ablation using only the NeuWave Certus&#xD;
      Microwave Ablation System. Patients in this study will come to their study site for the&#xD;
      ablation procedure. After the ablation procedure, the patient will be observed, which in most&#xD;
      cases is expected to be 2 to 3 hours, and afterwards may return home. If the Study Doctor&#xD;
      decides it is warranted for patient safety, the patient will remain in the hospital longer.&#xD;
&#xD;
      A minimum of one MRI of the liver must be taken at Baseline/Screening to ascertain tumor&#xD;
      type, location, and size. (Tumor size will be measured in longest diameter and the diameter&#xD;
      that is perpendicular to this longest diameter; tumor size must be measured with at least 2D&#xD;
      imaging.) Physicians who are experienced with tumor ablation will do all ablations&#xD;
      percutaneously using only the NeuWave Certus Ablation System. During the ablation, patients&#xD;
      will be under an anesthesia method as per the institution's SOC. Ultrasound and/or CT scan&#xD;
      will be used to guide the probe to the tumor and confirm accurate placement of the probe&#xD;
      prior to emitting the microwaves.&#xD;
&#xD;
      Within 7 days after ablation, contrast-enhanced MRI will be done to confirm the completion of&#xD;
      the ablation procedure. According to the standard practice at each study site, ablation&#xD;
      confirmation will be classified as:&#xD;
&#xD;
        -  complete tumor ablation with adequate margin (A0).&#xD;
&#xD;
        -  complete tumor ablation with insufficient margin (A1).&#xD;
&#xD;
        -  incomplete tumor ablation (A2). Over the course of 3 years, patients will return to&#xD;
           their study site for post ablation follow-up visits, which will be carried out per the&#xD;
           Schedule of Activities (see Table 1 at the end of the Synopsis). The follow-up schedule&#xD;
           will be based on the original ablation procedure date. A re-ablation for any reason will&#xD;
           not re-start or change the follow-up visit schedule.&#xD;
&#xD;
      At every follow-up visit, every patient will be scanned with at least one MRI to see if there&#xD;
      are any tumor foci at the edge of the ablation zone, which indicates tumor progression.&#xD;
      Repeat microwave ablation (using the Certus Microwave Ablation System only) may be performed&#xD;
      for recurrence of target tumor(s) or to achieve complete tumor ablation with adequate margin&#xD;
      (A0) of the target tumor(s) if the initial ablation had an insufficient margin, if the&#xD;
      treating physician deems appropriate and necessary.&#xD;
&#xD;
      While repeat ablations for a recurrence may be conducted at any point during the study&#xD;
      duration, repeat ablations to correct an ablative margin may only be performed within the&#xD;
      first 30 days of the original ablation (by Visit 3).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 17, 2019</start_date>
  <completion_date type="Anticipated">July 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">January 31, 2024</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Primary Technical Efficacy</measure>
    <time_frame>1 month (+/- 7 days)</time_frame>
    <description>defined as a combination of A0 ablations (complete tumor ablation with a surrounding 5 mm margin) and A1 ablations (complete tumor ablation with inadequate margins), based on contrast-enhanced MRI scans at 1 month (+/- 7 days) after the original ablation procedure.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Technical Success</measure>
    <time_frame>7 days</time_frame>
    <description>defined as a combination of A0 ablations (complete tumor ablation with a surrounding 5 mm margin) and A1 ablations (complete tumor ablation with inadequate margins) based on contrast-enhanced Magnetic Resonance Imaging (MRI) performed up to 7 days following the original ablation procedure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival</measure>
    <time_frame>1,3,6,9,12,18,24,30,36 months</time_frame>
    <description>defined as length of time from the original ablation procedure until any type of disease progression (i.e. local or distant).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary efficacy rate</measure>
    <time_frame>1,3,6,9,12,18,24,30,36 months</time_frame>
    <description>defined as the percentage of tumors that have undergone successful repeat ablation following identification of local tumor progression at any time during study follow up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall-survival,</measure>
    <time_frame>1,3,6,9,12,18,24,30,36 months</time_frame>
    <description>measured from the time of the original ablation procedure to the time of death or last follow-up, if death has not occurred.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Local tumor progression (LTP)</measure>
    <time_frame>1,3,6,9,12,18,24,30,36 months</time_frame>
    <description>evaluated at every visit after the ablation of the target tumor. LTP describes the appearance of tumor foci at the edge of the ablation zone, after at least one contrast-enhanced follow-up MRI scan has documented adequate ablation and an absence of viable tissue in the target tumor and surrounding ablation margin by using imaging criteria.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Safety Endpoint</measure>
    <time_frame>1,3,6,9,12,18,24,30,36 months</time_frame>
    <description>Adverse events (AEs) and serious adverse events (SAEs) reported at each analysis and cumulatively throughout the entire study period.</description>
  </other_outcome>
  <other_outcome>
    <measure>Numeric Pain Rating Scale</measure>
    <time_frame>7 days/1 month（±7days）</time_frame>
    <description>The Numeric Pain Rating Scale (NPRS) is a patient-reported outcome. Patients will complete this scale before the ablation procedure (measured at the Screening Visit), post ablation (within 7 days after ablation), and at the 1-month follow-up visit.&#xD;
This scale ranges from 0 (no pain) to 10 (worst possible pain).</description>
  </other_outcome>
  <other_outcome>
    <measure>EORTC QLQ-C30 Questionnaire</measure>
    <time_frame>7days/1,3,6,9,12,18,24,30,36 months</time_frame>
    <description>EORTC QLQ-C30 is a patient-reported questionnaire that assesses the health-related quality-of-life (QOL) of cancer patients. This questionnaire is assessed before the ablation procedure (measured at Screening Visit), post ablation (within 7 days after ablation), and at each follow-up visit.&#xD;
The questionnaire individual questions range in scores from 0 to 100 with a higher score correlating to a better quality of life for the patient for 'function' questions but correlates to worse symptoms for 'symptom' questions.</description>
  </other_outcome>
  <other_outcome>
    <measure>EORTC QLQ-HCC18 Questionnaire</measure>
    <time_frame>7days/1,3,6,9,12,18,24,30,36 months</time_frame>
    <description>EORTC QLQ-HCC18 is a patient-reported questionnaire that assesses the health-related quality-of-life (QOL) of hepatocellular cancer patients. This questionnaire is assessed before the ablation procedure (measured at Screening Visit), post ablation (within 7 days after ablation), and at each follow-up visit.&#xD;
All individual questions are scored from 0 to 100 with a higher score correlating with a more severe symptom or problem.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">135</enrollment>
  <condition>Liver Tumor</condition>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>Single-arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be treated with microwave ablation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Microwave ablation</intervention_name>
    <description>Subjects will be treated with microwave ablation.</description>
    <arm_group_label>Single-arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosed primary or recurrent HCC determined in accordance with the institution's SOC&#xD;
             procedure, a single tumor size up to 5 cm or a maximum of 3 tumors up to 3 cm per&#xD;
             tumor. Tumor size must be measured with at least 2-dimensional (2D) imaging.&#xD;
&#xD;
          -  Scheduled for microwave ablation of the liver.&#xD;
&#xD;
          -  Performance status 0-2 (Eastern Cooperative Oncology Group classification).&#xD;
&#xD;
          -  Functional hepatic reserve based on the Child-Pugh score (Class A or B).&#xD;
&#xD;
          -  Give voluntary, written informed consent to participate in this study and willing to&#xD;
             comply with study-related evaluation and procedure schedule.&#xD;
&#xD;
          -  At least 18 years of age.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. ASA score ≥ 4.&#xD;
&#xD;
          2. Active bacterial or fungal infections which are clinically significantly.&#xD;
&#xD;
          3. Chemotherapy or radiation therapy for HCC performed within 30 days prior to the study&#xD;
             procedure.&#xD;
&#xD;
          4. Patient with implantable pacemakers or other electronic implants.&#xD;
&#xD;
          5. Planned/ scheduled liver surgery.&#xD;
&#xD;
          6. Platelet count ≤ 50 × 109/L.&#xD;
&#xD;
          7. Patients with uncorrectable coagulopathy at time of screening based on investigator&#xD;
             judgement. Severe blood coagulation dysfunction (bleeding tendency, prothrombin time&#xD;
             [PT] was greater than normal control for 3~5 seconds, platelet count [PLT] was less&#xD;
             than 50x109/L, and the international normalized ratio [INR] was greater than 1.5).&#xD;
&#xD;
          8. Patient with renal failure and on renal dialysis.&#xD;
&#xD;
          9. Scheduled concurrent procedure other than MW ablation in the liver.&#xD;
&#xD;
         10. Pregnant or breast feeding.&#xD;
&#xD;
         11. Physical or psychological condition which would impair study participation.&#xD;
&#xD;
         12. Participation in any other interventional clinical study within 1 month before&#xD;
             screening and concurrently during the study.&#xD;
&#xD;
         13. The patient is judged unsuitable for study participation by the investigator for any&#xD;
             other reason.&#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>Ping Liang, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Leading PI</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jinhua Huang, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Co-PI</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Xiaoyan Xie, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Co-PI</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Bo Zhai, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>CO-PI</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sun Yat-sen University Cancer Center</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital，Sun Yat-sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chinese PLA General Hospital</name>
      <address>
        <city>Beijing</city>
        <zip>100089</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Renji Hospital, Shanghai Jiao Tong University School of Medicine</name>
      <address>
        <city>Shanghai</city>
        <zip>200120</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>November 30, 2018</study_first_submitted>
  <study_first_submitted_qc>December 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 21, 2018</study_first_posted>
  <last_update_submitted>September 11, 2023</last_update_submitted>
  <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HCC</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Hepatocellular</mesh_term>
  </condition_browse>
  <!-- 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/NCT03783871
org study id: NEU_2017_07
nct id: NCT03783871
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
This is a single-arm, prospective, multicenter, study. Individuals who are assessed for
      microwave (MW) ablation of HCC in accordance with their institution's standard of care (SOC),
      who meet study entry criteria and sign the informed consent, will be enrolled. The patients
      will be treated with MW ablation and afterwards followed for up to 36 months after the
      original ablation procedure to assess efficacy and safety. In addition to the final analysis
      after all enrolled patients complete the 36-month observation period, a summary of selected
      endpoints will be provided after all enrolled patients have completed each of the 1-month and
      12-month visits.

      To provide sites with an opportunity to get equal experience in the use of the Certus system,
      there will 3 patients treated as part of a run-in phase. These patients will only be included
      in the safety set.
Patients who have a single HCC tumor up to 5 cm or a maximum of 3 HCC tumors of up to 3 cm
      per tumor will receive the same procedure: microwave ablation using only the NeuWave Certus
      Microwave Ablation System. Patients in this study will come to their study site for the
      ablation procedure. After the ablation procedure, the patient will be observed, which in most
      cases is expected to be 2 to 3 hours, and afterwards may return home. If the Study Doctor
      decides it is warranted for patient safety, the patient will remain in the hospital longer.

      A minimum of one MRI of the liver must be taken at Baseline/Screening to ascertain tumor
      type, location, and size. (Tumor size will be measured in longest diameter and the diameter
      that is perpendicular to this longest diameter; tumor size must be measured with at least 2D
      imaging.) Physicians who are experienced with tumor ablation will do all ablations
      percutaneously using only the NeuWave Certus Ablation System. During the ablation, patients
      will be under an anesthesia method as per the institution's SOC. Ultrasound and/or CT scan
      will be used to guide the probe to the tumor and confirm accurate placement of the probe
      prior to emitting the microwaves.

      Within 7 days after ablation, contrast-enhanced MRI will be done to confirm the completion of
      the ablation procedure. According to the standard practice at each study site, ablation
      confirmation will be classified as:

        -  complete tumor ablation with adequate margin (A0).

        -  complete tumor ablation with insufficient margin (A1).

        -  incomplete tumor ablation (A2). Over the course of 3 years, patients will return to
           their study site for post ablation follow-up visits, which will be carried out per the
           Schedule of Activities (see Table 1 at the end of the Synopsis). The follow-up schedule
           will be based on the original ablation procedure date. A re-ablation for any reason will
           not re-start or change the follow-up visit schedule.

      At every follow-up visit, every patient will be scanned with at least one MRI to see if there
      are any tumor foci at the edge of the ablation zone, which indicates tumor progression.
      Repeat microwave ablation (using the Certus Microwave Ablation System only) may be performed
      for recurrence of target tumor(s) or to achieve complete tumor ablation with adequate margin
      (A0) of the target tumor(s) if the initial ablation had an insufficient margin, if the
      treating physician deems appropriate and necessary.

      While repeat ablations for a recurrence may be conducted at any point during the study
      duration, repeat ablations to correct an ablative margin may only be performed within the
      first 30 days of the original ablation (by Visit 3).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Primary Technical Efficacy
time frame: 1 month (+/- 7 days)
description: defined as a combination of A0 ablations (complete tumor ablation with a surrounding 5 mm margin) and A1 ablations (complete tumor ablation with inadequate margins), based on contrast-enhanced MRI scans at 1 month (+/- 7 days) after the original ablation procedure.
measure: Technical Success
time frame: 7 days
description: defined as a combination of A0 ablations (complete tumor ablation with a surrounding 5 mm margin) and A1 ablations (complete tumor ablation with inadequate margins) based on contrast-enhanced Magnetic Resonance Imaging (MRI) performed up to 7 days following the original ablation procedure.
measure: Progression-Free Survival
time frame: 1,3,6,9,12,18,24,30,36 months
description: defined as length of time from the original ablation procedure until any type of disease progression (i.e. local or distant).
measure: Secondary efficacy rate
time frame: 1,3,6,9,12,18,24,30,36 months
description: defined as the percentage of tumors that have undergone successful repeat ablation following identification of local tumor progression at any time during study follow up.
measure: Overall-survival,
time frame: 1,3,6,9,12,18,24,30,36 months
description: measured from the time of the original ablation procedure to the time of death or last follow-up, if death has not occurred.
measure: Local tumor progression (LTP)
time frame: 1,3,6,9,12,18,24,30,36 months
description: evaluated at every visit after the ablation of the target tumor. LTP describes the appearance of tumor foci at the edge of the ablation zone, after at least one contrast-enhanced follow-up MRI scan has documented adequate ablation and an absence of viable tissue in the target tumor and surrounding ablation margin by using imaging criteria.
measure: Safety Endpoint
time frame: 1,3,6,9,12,18,24,30,36 months
description: Adverse events (AEs) and serious adverse events (SAEs) reported at each analysis and cumulatively throughout the entire study period.
measure: Numeric Pain Rating Scale
time frame: 7 days/1 month（±7days）
description: The Numeric Pain Rating Scale (NPRS) is a patient-reported outcome. Patients will complete this scale before the ablation procedure (measured at the Screening Visit), post ablation (within 7 days after ablation), and at the 1-month follow-up visit.
This scale ranges from 0 (no pain) to 10 (worst possible pain).
measure: EORTC QLQ-C30 Questionnaire
time frame: 7days/1,3,6,9,12,18,24,30,36 months
description: EORTC QLQ-C30 is a patient-reported questionnaire that assesses the health-related quality-of-life (QOL) of cancer patients. This questionnaire is assessed before the ablation procedure (measured at Screening Visit), post ablation (within 7 days after ablation), and at each follow-up visit.
The questionnaire individual questions range in scores from 0 to 100 with a higher score correlating to a better quality of life for the patient for 'function' questions but correlates to worse symptoms for 'symptom' questions.
measure: EORTC QLQ-HCC18 Questionnaire
time frame: 7days/1,3,6,9,12,18,24,30,36 months
description: EORTC QLQ-HCC18 is a patient-reported questionnaire that assesses the health-related quality-of-life (QOL) of hepatocellular cancer patients. This questionnaire is assessed before the ablation procedure (measured at Screening Visit), post ablation (within 7 days after ablation), and at each follow-up visit.
All individual questions are scored from 0 to 100 with a higher score correlating with a more severe symptom or problem.
arm group label: Single-arm
arm group type: Experimental
description: Subjects will be treated with microwave ablation.
intervention type: Device
intervention name: Microwave ablation
description: Subjects will be treated with microwave ablation.
arm group label: Single-arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ping Liang, Doctor
role: Principal Investigator
affiliation: Leading PI
last name: Jinhua Huang, Doctor
role: Principal Investigator
affiliation: Co-PI
last name: Xiaoyan Xie, Doctor
role: Principal Investigator
affiliation: Co-PI
last name: Bo Zhai, Doctor
role: Principal Investigator
affiliation: CO-PI
facility: 
facility: 
facility: 
facility: 
country: China
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular