<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/NCT03758014</url>
  </required_header>
  <id_info>
    <org_study_id>LYS-GBM-01</org_study_id>
    <nct_id>NCT03758014</nct_id>
  </id_info>
  <brief_title>Studies of Chlorogenic Acid for Injection for Safety and Efficacy of Grade IV GBM Patients</brief_title>
  <official_title>A Randomized, Control, Open-label, Multicenter, Phase II/III Studies of Chlorogenic Acid for Injection for Safety and Efficacy of Grade IV GBM Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sichuan J.Z. Bio-chemical Science and Technology Development Co., Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sichuan J.Z. Bio-chemical Science and Technology Development Co., Ltd</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of phase II/III study: Determining the Overall Survival（OS）of Chlorogenic acid&#xD;
      for injection comparing to in the advanced Glioblastoma Patients through study completion（an&#xD;
      average of 18 months）after the first dose of chlorogenic acid for injection and Lomustine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chlorogenic acid (CHA) is a class 1 innovative small molecular natural drug, developed by&#xD;
      Sichuan Jiuzhang Biological Science and Technology Co., Ltd. The mechanism of broad-spectrum&#xD;
      antitumor activity is immunoregulation. After received the clinical trial approval issued by&#xD;
      CFDA, Jiuzhang Biotech successfully finished the phase I clinical studies of CHA for&#xD;
      injection in advanced GBM patients, focus on safety, PK, and preliminary efficacy evaluation.&#xD;
&#xD;
      The results of phase I data showed that CHA had good safety, the main adverse effect was&#xD;
      induration, no other serious adverse effects. PK exhibited that CHA had a rapid metabolism&#xD;
      character (t1/2 = 1-1.5 h). In addition, there were no accumulative side effects for&#xD;
      long-term use. To the investigators' surprise, the preliminary efficacy evaluation was&#xD;
      amazing, there were 1 case CR and 1 case PR. The median OS of grade IV GBM patients was 21.4&#xD;
      months in effective dose group, which was much better than that of the historical reported&#xD;
      data.The purpose of phase II/III study: Determining the Overall Survival（OS）of Chlorogenic&#xD;
      acid for injection comparing to in the advanced Glioblastoma Patients through study&#xD;
      completion（an average of 18 months）after the first dose of chlorogenic acid for injection and&#xD;
      Lomustine .&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 27, 2018</start_date>
  <completion_date type="Anticipated">April 30, 2021</completion_date>
  <primary_completion_date type="Anticipated">October 30, 2020</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Survival（OS）</measure>
    <time_frame>Through study completion（an average of 18 months）after the first dose of chlorogenic acid for injection and Lomustine</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>progress free survival(PFS)</measure>
    <time_frame>Through study completion（an average of 18 months）after the first dose of chlorogenic acid for injection and Lomustine</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>disease control rate（DCR)</measure>
    <time_frame>Within the first 10 weeks after the first dose of chlorogenic acid for injection and Lomustine</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>objective response rate (ORR)</measure>
    <time_frame>Within the first 10 weeks after the first dose of chlorogenic acid for injection and Lomustine</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Karnofsky score standard</measure>
    <time_frame>Through study completion（an average of 18 months）after the first dose of chlorogenic acid for injection and Lomustine</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Montreal Cognitive Assessment score standard</measure>
    <time_frame>Through study completion（an average of 18 months）after the first dose of chlorogenic acid for injection and Lomustine</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>GBM</condition>
  <arm_group>
    <arm_group_label>Chlorogenic Acid for Injection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 mg/kg per day, injection for 28 days，5 weeks per circle; max. 8 circles</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lomustine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>110 mg/m2 taken as a single oral dose every 6 weeks; max. 4 circles</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Chlorogenic acid for Injection</intervention_name>
    <description>Chlorogenic acid (CHA) is a class 1 innovative small molecular natural drug, developed by Sichuan Jiuzhang Biological Science and Technology Co., Ltd. The mechanism of broad-spectrum antitumor activity is immunoregulation.</description>
    <arm_group_label>Chlorogenic Acid for Injection</arm_group_label>
    <other_name>CHA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lomustine</intervention_name>
    <description>Lomustine (INN), abbreviated as CCNU (original brand name (formerly available) is CeeNU, now marketed as Gleostine), is an alkylating nitrosourea compound used in chemotherapy. It is closely related to semustine and is in the same family as streptozotocin. It is a highly lipid-soluble drug, thus it crosses the blood-brain barrier. This property makes it ideal for treating brain tumors, which is its primary use.</description>
    <arm_group_label>Lomustine</arm_group_label>
    <other_name>CCNU</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18;&#xD;
&#xD;
          2. KPS ≥ 60;&#xD;
&#xD;
          3. Recurrent GBM;&#xD;
&#xD;
          4. Estimated lifetime ≥ 3 months；&#xD;
&#xD;
          5. Female patients with negative pregnant test, and male/female patients of reproductive&#xD;
             age without pregnancy planning in the next 12 months;&#xD;
&#xD;
          6. Volunteered for the phase 2 trial and sign the informed consent without protest.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients who have received the therapy of chemotherapy or radical radiotherapy within&#xD;
             1 month before enrollment;&#xD;
&#xD;
          2. Pregnant or breast-feeding women, or patients(male and female) who have pregnancy&#xD;
             plan;&#xD;
&#xD;
          3. Patients who had received a therapy of another investigational drug within 1 month；&#xD;
&#xD;
          4. Known active hepatitis B/hepatitis C, positive HIV/ syphilis antibody;&#xD;
&#xD;
          5. Patients who have received therapy of major surgery within 4 weeks or biopsy surgery&#xD;
             within 1 week before enrollment;&#xD;
&#xD;
          6. Patient who need long term treatment of cortical hormone or other immunosuppressive&#xD;
             drugs such as visceral organ transplanters；&#xD;
&#xD;
          7. Patients who have sufficient baseline organ function and whose laboratory data can&#xD;
             meet the following criteria at the enrollment:1)PLT count&lt;80×10~9/L； 2)NEUT#&#xD;
             count&lt;1.5×10~9/L ；3)HGB count&lt;90g/L；4)Total bilirubin &gt;1.5 times of ULN；5)ALT/AST &gt;1.5&#xD;
             times of ULN；&#xD;
&#xD;
          8. History of drug abuse；&#xD;
&#xD;
          9. Patients who was treated with Immunologic drugs（DC/CIK/CTL/PD-（L）1） in 3 months;&#xD;
&#xD;
         10. Patients who are false progressers；&#xD;
&#xD;
         11. Patients who can not be received MRI examination；&#xD;
&#xD;
         12. Patients who had severe trauma or infectious diseases within 4 weeks；&#xD;
&#xD;
         13. Patients who had cerebral stroke or Transient ischemic attack within 6 months；&#xD;
&#xD;
         14. Patients who were performed important operations within 4 weeks；&#xD;
&#xD;
         15. Uncontrollable psychopaths;&#xD;
&#xD;
         16. Patients who had other advanced cancers within 5 years；&#xD;
&#xD;
         17. Patients who had grade III or IV heart failure within 6 months；&#xD;
&#xD;
         18. Other patients judged ineligible for enrollment in the study by the investigator&#xD;
             (sub-investigator).&#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>Wenbin Li</last_name>
    <role>Study Director</role>
    <affiliation>Beijing Tian Tan Hospital，Capital Medical University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Wenbin Li</last_name>
    <phone>8615301377998</phone>
    <email>neure55@126.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Zhuang Kang</last_name>
    <phone>8615011281069</phone>
    <email>kzhaoren1984@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Beijing Tiantan Hospital, Capital Medical University</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wenbin Li</last_name>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>October 21, 2018</study_first_submitted>
  <study_first_submitted_qc>November 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>November 27, 2018</last_update_submitted>
  <last_update_submitted_qc>November 27, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 29, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lomustine</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/NCT03758014
org study id: LYS-GBM-01
nct id: NCT03758014
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The purpose of phase II/III study: Determining the Overall Survival（OS）of Chlorogenic acid
      for injection comparing to in the advanced Glioblastoma Patients through study completion（an
      average of 18 months）after the first dose of chlorogenic acid for injection and Lomustine.
Chlorogenic acid (CHA) is a class 1 innovative small molecular natural drug, developed by
      Sichuan Jiuzhang Biological Science and Technology Co., Ltd. The mechanism of broad-spectrum
      antitumor activity is immunoregulation. After received the clinical trial approval issued by
      CFDA, Jiuzhang Biotech successfully finished the phase I clinical studies of CHA for
      injection in advanced GBM patients, focus on safety, PK, and preliminary efficacy evaluation.

      The results of phase I data showed that CHA had good safety, the main adverse effect was
      induration, no other serious adverse effects. PK exhibited that CHA had a rapid metabolism
      character (t1/2 = 1-1.5 h). In addition, there were no accumulative side effects for
      long-term use. To the investigators' surprise, the preliminary efficacy evaluation was
      amazing, there were 1 case CR and 1 case PR. The median OS of grade IV GBM patients was 21.4
      months in effective dose group, which was much better than that of the historical reported
      data.The purpose of phase II/III study: Determining the Overall Survival（OS）of Chlorogenic
      acid for injection comparing to in the advanced Glioblastoma Patients through study
      completion（an average of 18 months）after the first dose of chlorogenic acid for injection and
      Lomustine .
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Investigator)
measure: Overall Survival（OS）
time frame: Through study completion（an average of 18 months）after the first dose of chlorogenic acid for injection and Lomustine
measure: progress free survival(PFS)
time frame: Through study completion（an average of 18 months）after the first dose of chlorogenic acid for injection and Lomustine
measure: disease control rate（DCR)
time frame: Within the first 10 weeks after the first dose of chlorogenic acid for injection and Lomustine
measure: objective response rate (ORR)
time frame: Within the first 10 weeks after the first dose of chlorogenic acid for injection and Lomustine
measure: Karnofsky score standard
time frame: Through study completion（an average of 18 months）after the first dose of chlorogenic acid for injection and Lomustine
measure: Montreal Cognitive Assessment score standard
time frame: Through study completion（an average of 18 months）after the first dose of chlorogenic acid for injection and Lomustine
arm group label: Chlorogenic Acid for Injection
arm group type: Experimental
description: 3 mg/kg per day, injection for 28 days，5 weeks per circle; max. 8 circles
arm group label: Lomustine
arm group type: Active Comparator
description: 110 mg/m2 taken as a single oral dose every 6 weeks; max. 4 circles
intervention type: Drug
intervention name: Chlorogenic acid for Injection
description: Chlorogenic acid (CHA) is a class 1 innovative small molecular natural drug, developed by Sichuan Jiuzhang Biological Science and Technology Co., Ltd. The mechanism of broad-spectrum antitumor activity is immunoregulation.
arm group label: Chlorogenic Acid for Injection
other name: CHA
intervention type: Drug
intervention name: Lomustine
description: Lomustine (INN), abbreviated as CCNU (original brand name (formerly available) is CeeNU, now marketed as Gleostine), is an alkylating nitrosourea compound used in chemotherapy. It is closely related to semustine and is in the same family as streptozotocin. It is a highly lipid-soluble drug, thus it crosses the blood-brain barrier. This property makes it ideal for treating brain tumors, which is its primary use.
arm group label: Lomustine
other name: CCNU
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Wenbin Li
role: Study Director
affiliation: Beijing Tian Tan Hospital，Capital Medical University
last name: Wenbin Li
phone: 8615301377998
email: neure55@126.com
last name: Zhuang Kang
phone: 8615011281069
email: kzhaoren1984@163.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Lomustine
sharing ipd: No