<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/NCT03769129</url>
  </required_header>
  <id_info>
    <org_study_id>ZZWMAICI-005</org_study_id>
    <nct_id>NCT03769129</nct_id>
  </id_info>
  <brief_title>Evaluating the Safety and Efficacy of Pembrolizumab Combined With MWA for Advanced NSCLC</brief_title>
  <official_title>A Prospective，Single Center, Randomized Control，Phase III Clinical Study for Evaluating the Safety and Efficacy of Pembrolizumab Combined With MWA for Patients With Stage ⅢB-Ⅳ NSCLC Who Failed With First-line Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Second Affiliated Hospital of Guangzhou Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Second Affiliated Hospital of Guangzhou Medical University</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>
      This is a prospective, randomized, single clinical study designed to evaluate its safety and&#xD;
      efficacy by using Microwave Ablation combine with Pembrolizumab in patients with Stage ⅢB-Ⅳ&#xD;
      Non-small Cell Lung.Cancer (NSCLC) who failed with first-line therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Lung cancer is one of the most common malignant tumors in the world and has become the No. 1&#xD;
      cause of death from malignant tumors in China. Non-small cell lung cancer (NSCLC) includes&#xD;
      squamous cell carcinomas, adenocarcinomas, and large cell carcinomas and accounts for about&#xD;
      80-85% of all lung cancers. NSCLC cancer cells divide slowly in a diffusive manner and&#xD;
      metastasize at a relatively late stage compared to small cell carcinomas. A majority of&#xD;
      patients with NSCLC are already in advanced stages and have a low 5-year survival rate.&#xD;
&#xD;
      Treatments for advanced NSCLC include chemotherapy ,targeted therapies and immunotherapy. The&#xD;
      microwave ablation is the good choice for patients who cannot tolerate surgical resection. A&#xD;
      large number of studies have shown that local minimally invasive ablation therapy within a&#xD;
      certain temperature range can stimulate the body to produce an immune response to varying&#xD;
      degrees. The study found that for a variety of malignant tumor models, thermal ablation local&#xD;
      treatment of in situ tumors, while the disappearance of other metastatic lesions, and treated&#xD;
      mice are resistant to secondary vaccination of the same tumor, proving that thermal ablation&#xD;
      therapy stimulates long-lasting Anti-tumor immunity. Pembrolizumab are representative drugs&#xD;
      for immunosuppressive agents, and its indications have been approved in various types of&#xD;
      tumors, including advanced melanoma, advanced squamous non-small cell lung cancer, advanced&#xD;
      renal cell carcinoma, and classical Hodgkin's lymphoma and late recurrent head and neck&#xD;
      squamous cell carcinoma patients. Whether the combination of the two can cause a stronger&#xD;
      anti-tumor immune response in the body. However, the flexibility, safety and efficacy of&#xD;
      using Microwave Ablation combine with Pembrolizumab in NSCLC patients are still unclear.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 1, 2018</start_date>
  <completion_date type="Anticipated">November 1, 2029</completion_date>
  <primary_completion_date type="Anticipated">November 1, 2026</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall survival</measure>
    <time_frame>2 years</time_frame>
    <description>Overall survival (OS) will be defined as the elapsed time from the enrollment to death from any cause. For surviving patients, follow-up will be censored at the date of last contact (or last date known to be alive). Follow-up for OS will occur every 12 weeks (±1 month) until death or withdrawal of consent from the study.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events（Safety）</measure>
    <time_frame>2 years</time_frame>
    <description>All the local reactions, systemic reactions, all the adverse events and serious adverse events obtained during the study of all the patients included in the first stage and the second stage of this study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival</measure>
    <time_frame>2 years</time_frame>
    <description>From enrollment to progression of disease.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Non Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Microwave ablation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Firstly, microwave ablation performed at our department by interventional radiologist, then Pembrolizumab will be administered at a dose of 2 mg/kg every three weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pembrolizumab</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Firstly, pembrolizumab was administered intravenously at a dose of 2 mg/kg. Then microwave ablation will be performed if there is no immune-related adverse reactions. Pembrolizumab will also be continuously administered every three weeks until the imaging evaluation of the disease progress.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Pembrolizumab</description>
    <arm_group_label>Microwave ablation</arm_group_label>
    <arm_group_label>Pembrolizumab</arm_group_label>
    <other_name>Keytruda</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>microwave ablation</intervention_name>
    <description>microwave ablation</description>
    <arm_group_label>Microwave ablation</arm_group_label>
    <arm_group_label>Pembrolizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Pathologically diagnosed IIIB or IV non-small cell lung cancer.&#xD;
&#xD;
          2. Previously accepted first-line standard treatment failure or recurrence&#xD;
&#xD;
          3. At least one measurable lesion.&#xD;
&#xD;
          4. The patient has not received any other anti-cancer treatment within four weeks.&#xD;
&#xD;
          5. Any gender, age ≥18 years&#xD;
&#xD;
          6. ECOG PS : 0-2 points&#xD;
&#xD;
          7. Expected survival ≥ 6 months&#xD;
&#xD;
          8. The level of organ function meets the following criteria.&#xD;
&#xD;
        (1) subject to the standard blood test: ANC ≥ 1.5×109 / L, PLT ≥ 50×109 / L, Hb ≥ 90g/L.&#xD;
&#xD;
        (2) biochemical tests must meet the following criteria: TBIL&lt;1.5×ULN, ALT, AST &lt;2.5×ULN (&#xD;
        if liver metastasis ALT, AST can be &lt;5×ULN), BUN, and Cr ≤ 1×ULN).&#xD;
&#xD;
        9. Female patients in child bearing period must have evidence of negative pregnancy test,&#xD;
        and agree to take effective contraceptive measures until 6months after therapy.&#xD;
&#xD;
        10. Subjects volunteered to join the study, signed informed consent, good compliance, with&#xD;
        follow-up.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with two or more kinds of tumors.&#xD;
&#xD;
          2. Patients with active viral or bacterial infection, and have failed to be controlled by&#xD;
             anti-infective treatment.&#xD;
&#xD;
          3. Patients with seropositive response of Human immunodeficiency virus (HIV) and&#xD;
             syphilis, or fail to control the hepatitis B virus or hepatitis C virus infection.&#xD;
&#xD;
          4. Patients with active rheumatic diseases, organ transplantation and other diseases&#xD;
             affecting the immune system seriously.&#xD;
&#xD;
          5. Patients with severe heart and lung dysfunction.&#xD;
&#xD;
          6. Patients with severe chronic diseases of kidney, liver and other important organs.&#xD;
&#xD;
          7. Patients with any other serious illness that the investigators consider it will may&#xD;
             affect the patient's treatments, follow-up or assessment, including any uncontrolled&#xD;
             clinically significant neurological or psychiatric disorders, immunoregulatory&#xD;
             diseases, metabolic diseases, infectious diseases and so on.&#xD;
&#xD;
          8. Patients who take part in clinical trials of other drugs or biological therapy at&#xD;
             present or within 30 days before enrollment.&#xD;
&#xD;
          9. Patients who need long-term use of immunosuppressive drugs or patients who are&#xD;
             undergoing treatment of autoimmune diseases.&#xD;
&#xD;
         10. Patients who need long-term use of glucocorticoid.&#xD;
&#xD;
         11. Women patients in gestation period or suckling period.&#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>zhang zhenfeng, MD,PHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Second Affiliated Hospital of Guangzhou Medical University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>zhang zhenfeng, MD,PHD</last_name>
    <phone>02034153532</phone>
    <email>zhangzhf@gzhmu.edu.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>CHEN deji, MD,PHD</last_name>
    <phone>02034153532</phone>
    <email>chendeji2003@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>zhang Zhenfeng</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zhang Zhenfeng</last_name>
      <phone>13202005598</phone>
      <email>zhangzhf@gzhmu.edu.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>November 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 6, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <last_update_submitted>February 26, 2023</last_update_submitted>
  <last_update_submitted_qc>February 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Microwave ablation</keyword>
  <keyword>Pembrolizumab</keyword>
  <keyword>NSCLC</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Don not plan</ipd_description>
  </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/NCT03769129
org study id: ZZWMAICI-005
nct id: NCT03769129
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a prospective, randomized, single clinical study designed to evaluate its safety and
      efficacy by using Microwave Ablation combine with Pembrolizumab in patients with Stage ⅢB-Ⅳ
      Non-small Cell Lung.Cancer (NSCLC) who failed with first-line therapy.
Lung cancer is one of the most common malignant tumors in the world and has become the No. 1
      cause of death from malignant tumors in China. Non-small cell lung cancer (NSCLC) includes
      squamous cell carcinomas, adenocarcinomas, and large cell carcinomas and accounts for about
      80-85% of all lung cancers. NSCLC cancer cells divide slowly in a diffusive manner and
      metastasize at a relatively late stage compared to small cell carcinomas. A majority of
      patients with NSCLC are already in advanced stages and have a low 5-year survival rate.

      Treatments for advanced NSCLC include chemotherapy ,targeted therapies and immunotherapy. The
      microwave ablation is the good choice for patients who cannot tolerate surgical resection. A
      large number of studies have shown that local minimally invasive ablation therapy within a
      certain temperature range can stimulate the body to produce an immune response to varying
      degrees. The study found that for a variety of malignant tumor models, thermal ablation local
      treatment of in situ tumors, while the disappearance of other metastatic lesions, and treated
      mice are resistant to secondary vaccination of the same tumor, proving that thermal ablation
      therapy stimulates long-lasting Anti-tumor immunity. Pembrolizumab are representative drugs
      for immunosuppressive agents, and its indications have been approved in various types of
      tumors, including advanced melanoma, advanced squamous non-small cell lung cancer, advanced
      renal cell carcinoma, and classical Hodgkin's lymphoma and late recurrent head and neck
      squamous cell carcinoma patients. Whether the combination of the two can cause a stronger
      anti-tumor immune response in the body. However, the flexibility, safety and efficacy of
      using Microwave Ablation combine with Pembrolizumab in NSCLC patients are still unclear.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall survival
time frame: 2 years
description: Overall survival (OS) will be defined as the elapsed time from the enrollment to death from any cause. For surviving patients, follow-up will be censored at the date of last contact (or last date known to be alive). Follow-up for OS will occur every 12 weeks (±1 month) until death or withdrawal of consent from the study.
measure: Incidence of Treatment-Emergent Adverse Events（Safety）
time frame: 2 years
description: All the local reactions, systemic reactions, all the adverse events and serious adverse events obtained during the study of all the patients included in the first stage and the second stage of this study
measure: Progression-Free Survival
time frame: 2 years
description: From enrollment to progression of disease.
arm group label: Microwave ablation
arm group type: Experimental
description: Firstly, microwave ablation performed at our department by interventional radiologist, then Pembrolizumab will be administered at a dose of 2 mg/kg every three weeks.
arm group label: Pembrolizumab
arm group type: Other
description: Firstly, pembrolizumab was administered intravenously at a dose of 2 mg/kg. Then microwave ablation will be performed if there is no immune-related adverse reactions. Pembrolizumab will also be continuously administered every three weeks until the imaging evaluation of the disease progress.
intervention type: Drug
intervention name: Pembrolizumab
description: Pembrolizumab
arm group label: Microwave ablation
arm group label: Pembrolizumab
other name: Keytruda
intervention type: Procedure
intervention name: microwave ablation
description: microwave ablation
arm group label: Microwave ablation
arm group label: Pembrolizumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: zhang zhenfeng, MD,PHD
role: Principal Investigator
affiliation: Second Affiliated Hospital of Guangzhou Medical University
last name: zhang zhenfeng, MD,PHD
phone: 02034153532
email: zhangzhf@gzhmu.edu.cn
last name: CHEN deji, MD,PHD
phone: 02034153532
email: chendeji2003@163.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Pembrolizumab
sharing ipd: No
ipd description: Don not plan