<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/NCT04413227</url>
  </required_header>
  <id_info>
    <org_study_id>SIM181202-PEGENDO-102</org_study_id>
    <nct_id>NCT04413227</nct_id>
  </id_info>
  <brief_title>A Phase Ib Study With Pegylated Recombinant Human Endostatin in Advanced / Metastatic NSCLC or Other Solid Tumors</brief_title>
  <official_title>A Phase Ⅰb Study Evaluating the Safety, Tolerability and Pharmacokinetics of Pegylated Recombinant Human Endostatin (PEG-ENDO) in Subjects With Advanced / Metastatic Non-small Cell Lung Cancer (NSCLC) or Other Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu Simcere Pharmaceutical Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jiangsu Simcere Pharmaceutical Co., Ltd.</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>
      The primary purpose of this study is to examine the safety, tolerability and pharmacokinetics&#xD;
      of PEG-ENDO in combination with docetaxel in subjects previously treated or untreated&#xD;
      (standard therapy is not suitable or without standard therapy) for advanced or metatatic&#xD;
      non-small cell lung cancer (NSCLC) or other solid tumors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multicenter, open-label, dose-escalation study in subjects with advanced or&#xD;
      metatatic non-small cell lung cancer (NSCLC) or other solid tumors.There will be five cohorts&#xD;
      planning as following:&#xD;
&#xD;
      cohort 1: PEG-ENDO 1 mg/kg+Docetaxel 75 mg/m2,once every 3 weeks at day 1 cohort 2: PEG-ENDO&#xD;
      2mg/kg+Docetaxel 75 mg/m2,once every 3 weeks at day 1 cohort 3: PEG-ENDO 4 mg/kg+Docetaxel 75&#xD;
      mg/m2,once every 3 weeks at day 1 cohort 4: PEG-ENDO 6 mg/kg+Docetaxel75 mg/m2,once every 3&#xD;
      weeks at day 1 cohort 5: PEG-ENDO 8 mg/kg+Docetaxel75 mg/m2, once every 3 weeks at day 1&#xD;
&#xD;
      * Every 3 weeks as a treatment cycle. Subjects received only PEG-ENDO in the first cycle. For&#xD;
      second cycle or the higher, they received a combination therapy of PEG-ENDO and docetaxel.&#xD;
      Docetaxel was limited in 4 or 6 cycles。 The observation period of DLT was the 21 days after&#xD;
      the first administration of PEG-ENDO. During the observation period of DLT (cycle 1),&#xD;
      subjects only receive the corresponding dose of PEG-ENDO , for the second cycle and higher&#xD;
      ,they will treated with the combination of PEG-ENDO and Docetaxel until disease progression&#xD;
      (PD) or intolerance . Docetaxel was limited in 4 or 6 cycles。&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 2, 2020</start_date>
  <completion_date type="Anticipated">September 30, 2021</completion_date>
  <primary_completion_date type="Anticipated">May 31, 2021</primary_completion_date>
  <phase>Phase 1</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>Dose Limiting Toxicities (DLT)</measure>
    <time_frame>First 21days for dosing（Cycle1，each cycle is 21 days)</time_frame>
    <description>Incidence of Dose Limiting Toxicity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse Event(AE)</measure>
    <time_frame>From the time the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment</time_frame>
    <description>Incidence of Adverse Events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serious Adverse Event(SAE)</measure>
    <time_frame>From the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment</time_frame>
    <description>Incidence of Serious Adverse Events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Laborarory test abnormality</measure>
    <time_frame>From the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment</time_frame>
    <description>Incidence of clinically significant laboratory abnormalities</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vital signs abnormality</measure>
    <time_frame>From the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment</time_frame>
    <description>Incidence of vital signs abnormalities</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Electrocardiogram(ECG) abnormality</measure>
    <time_frame>From the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment</time_frame>
    <description>Incidence of clinically significant ECG abnormalities</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serum concentration</measure>
    <time_frame>Pharmacokinetics(PK) blood samples are collected at pre-dose, post-dose 0,1,4,8,24,48,96,168,336,480h of cycle1 and cycle5,respectively. And the pre-dose, post-dose 0h of other required cycles.</time_frame>
    <description>Serum concentration of PEG-ENDO</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The maximum (or peak) serum ,Cmax</measure>
    <time_frame>Pharmacokinetics(PK) blood samples are collected at pre-dose, post-dose 0,1,4,8,24,48,96,168,336,480h of cycle1 and cycle5,respectively. And the pre-dose, post-dose 0h of other required cycles.</time_frame>
    <description>Cmax of PEG-ENDO following dose concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC</measure>
    <time_frame>Pharmacokinetics(PK) blood samples are collected at pre-dose, post-dose 0,1,4,8,24,48,96,168,336,480h of cycle1 and cycle5,respectively. And the pre-dose, post-dose 0h of other required cycles.</time_frame>
    <description>The area under the plot of serum concentration of drug (not logarithm of the concentration) against time after drug administration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>other PK parameters</measure>
    <time_frame>Pharmacokinetics(PK) blood samples are collected at pre-dose, post-dose 0,1,4,8,24,48,96,168,336,480h of cycle1 and cycle5,respectively. And the pre-dose, post-dose 0h of other required cycles.</time_frame>
    <description>The other PK parameters (if applicable).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Tolerated Dose(MTD)</measure>
    <time_frame>First 21days for dosing（Cycle1，each cycle is 21 days)</time_frame>
    <description>To determine the Maximum Tolerated Dose (MTD) of PEG-ENDO in subjects with Advanced / Metastatic NSCLC or Other Solid Tumors</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate(ORR)</measure>
    <time_frame>at least 12 weeks</time_frame>
    <description>ORR is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response(DOR)</measure>
    <time_frame>Estimated at 4 months after fist documented PD or CR</time_frame>
    <description>DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Estimated at 4 months.</time_frame>
    <description>PFS is defined as time from date of first dose of study treatment to date of first documented disease progression or death due to any cause determined by by Investigator assessment in accordance to RECIST 1.1</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>NSCLC</condition>
  <condition>Solid Tumor</condition>
  <arm_group>
    <arm_group_label>PEG-ENDO+Docetaxel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PEG-ENDO( 1 mg/kg or 2mg/kg or 4mg/kg or 6mg/kg or 8mg/kg）+Docetaxel 75 mg/m2，once every 3 weeks at day 1</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pegylated Recombinant Human Endostatin（PEG-ENDO）</intervention_name>
    <description>PEG-ENDO 1 mg/kg or 2 mg/kg or 4 mg/kg or 6 mg/kg or 8 mg/kg+Docetaxel 75 mg/m2，once every 3 weeks at day 1</description>
    <arm_group_label>PEG-ENDO+Docetaxel</arm_group_label>
    <other_name>Docetaxel</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provision of signed and dated, written informed consent.&#xD;
&#xD;
          2. 18-70years old, male or female.&#xD;
&#xD;
          3. Histological or cytological confirmation diagnosis of Non Small Cell Lung&#xD;
             Cancer(NSCLC) or other solid tumor, previous treated with standard therapy , or&#xD;
             standard therapy not suitabl ,or without standard therapy.&#xD;
&#xD;
          4. At least one measurable disease according to RECIST v1.1.&#xD;
&#xD;
          5. Life expectancy of at least 3 months.&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.&#xD;
&#xD;
          7. Demonstrate adequate organ function -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. uncontrolled primary CNS tumors, brain metastases, or meningeal metastases.&#xD;
&#xD;
          2. Evidence of a tumor that compresses or invades major blood vessels.&#xD;
&#xD;
          3. History of hemoptysis (&gt;1/2 teaspoon per event) or severe bleeding or evidence of&#xD;
             bleeding disorders in the last 3 months.&#xD;
&#xD;
          4. Clinically significant active cardiovascular disease within 6 months prior to planned&#xD;
             start of PEG-ENDO.&#xD;
&#xD;
          5. Prior treatment with anti-agiogenetic agent.&#xD;
&#xD;
          6. Pregnant female patients; breastfeeding female patients.&#xD;
&#xD;
             -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Huang Dingzhi, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tianjin Medical University Cancer Institute &amp; Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Li Lin, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beijing Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Huang Dingzhi, Ph.D</last_name>
    <phone>02223340123</phone>
    <phone_ext>3220</phone_ext>
    <email>dingzhih72@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Beijing Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100005</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Li Lin, Ph.D</last_name>
      <phone>010-85136714</phone>
      <email>lilin_51@163.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Tianjin medical university cancer institute&amp;hospital</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <zip>300060</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Huang Dingzhi, Ph.D</last_name>
      <phone>02223340123</phone>
      <phone_ext>3220</phone_ext>
      <email>dingzhih72@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 25, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>May 28, 2020</last_update_submitted>
  <last_update_submitted_qc>May 28, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>pegylated recombinant human endostatin (PEG-ENDO)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <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>Docetaxel</mesh_term>
    <mesh_term>Endostatins</mesh_term>
  </intervention_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/NCT04413227
org study id: SIM181202-PEGENDO-102
nct id: NCT04413227
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary purpose of this study is to examine the safety, tolerability and pharmacokinetics
      of PEG-ENDO in combination with docetaxel in subjects previously treated or untreated
      (standard therapy is not suitable or without standard therapy) for advanced or metatatic
      non-small cell lung cancer (NSCLC) or other solid tumors.
This is a multicenter, open-label, dose-escalation study in subjects with advanced or
      metatatic non-small cell lung cancer (NSCLC) or other solid tumors.There will be five cohorts
      planning as following:

      cohort 1: PEG-ENDO 1 mg/kg+Docetaxel 75 mg/m2,once every 3 weeks at day 1 cohort 2: PEG-ENDO
      2mg/kg+Docetaxel 75 mg/m2,once every 3 weeks at day 1 cohort 3: PEG-ENDO 4 mg/kg+Docetaxel 75
      mg/m2,once every 3 weeks at day 1 cohort 4: PEG-ENDO 6 mg/kg+Docetaxel75 mg/m2,once every 3
      weeks at day 1 cohort 5: PEG-ENDO 8 mg/kg+Docetaxel75 mg/m2, once every 3 weeks at day 1

      * Every 3 weeks as a treatment cycle. Subjects received only PEG-ENDO in the first cycle. For
      second cycle or the higher, they received a combination therapy of PEG-ENDO and docetaxel.
      Docetaxel was limited in 4 or 6 cycles。 The observation period of DLT was the 21 days after
      the first administration of PEG-ENDO. During the observation period of DLT (cycle 1),
      subjects only receive the corresponding dose of PEG-ENDO , for the second cycle and higher
      ,they will treated with the combination of PEG-ENDO and Docetaxel until disease progression
      (PD) or intolerance . Docetaxel was limited in 4 or 6 cycles。
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose Limiting Toxicities (DLT)
time frame: First 21days for dosing（Cycle1，each cycle is 21 days)
description: Incidence of Dose Limiting Toxicity
measure: Adverse Event(AE)
time frame: From the time the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment
description: Incidence of Adverse Events
measure: Serious Adverse Event(SAE)
time frame: From the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment
description: Incidence of Serious Adverse Events
measure: Laborarory test abnormality
time frame: From the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment
description: Incidence of clinically significant laboratory abnormalities
measure: Vital signs abnormality
time frame: From the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment
description: Incidence of vital signs abnormalities
measure: Electrocardiogram(ECG) abnormality
time frame: From the subjects signed the Informed Consent Form to 28 days after the end of the study drug treatment
description: Incidence of clinically significant ECG abnormalities
measure: Serum concentration
time frame: Pharmacokinetics(PK) blood samples are collected at pre-dose, post-dose 0,1,4,8,24,48,96,168,336,480h of cycle1 and cycle5,respectively. And the pre-dose, post-dose 0h of other required cycles.
description: Serum concentration of PEG-ENDO
measure: The maximum (or peak) serum ,Cmax
time frame: Pharmacokinetics(PK) blood samples are collected at pre-dose, post-dose 0,1,4,8,24,48,96,168,336,480h of cycle1 and cycle5,respectively. And the pre-dose, post-dose 0h of other required cycles.
description: Cmax of PEG-ENDO following dose concentration.
measure: AUC
time frame: Pharmacokinetics(PK) blood samples are collected at pre-dose, post-dose 0,1,4,8,24,48,96,168,336,480h of cycle1 and cycle5,respectively. And the pre-dose, post-dose 0h of other required cycles.
description: The area under the plot of serum concentration of drug (not logarithm of the concentration) against time after drug administration.
measure: other PK parameters
time frame: Pharmacokinetics(PK) blood samples are collected at pre-dose, post-dose 0,1,4,8,24,48,96,168,336,480h of cycle1 and cycle5,respectively. And the pre-dose, post-dose 0h of other required cycles.
description: The other PK parameters (if applicable).
measure: Maximum Tolerated Dose(MTD)
time frame: First 21days for dosing（Cycle1，each cycle is 21 days)
description: To determine the Maximum Tolerated Dose (MTD) of PEG-ENDO in subjects with Advanced / Metastatic NSCLC or Other Solid Tumors
measure: Overall Response Rate(ORR)
time frame: at least 12 weeks
description: ORR is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
measure: Duration of Response(DOR)
time frame: Estimated at 4 months after fist documented PD or CR
description: DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1
measure: Progression-free survival (PFS)
time frame: Estimated at 4 months.
description: PFS is defined as time from date of first dose of study treatment to date of first documented disease progression or death due to any cause determined by by Investigator assessment in accordance to RECIST 1.1
arm group label: PEG-ENDO+Docetaxel
arm group type: Experimental
description: PEG-ENDO( 1 mg/kg or 2mg/kg or 4mg/kg or 6mg/kg or 8mg/kg）+Docetaxel 75 mg/m2，once every 3 weeks at day 1
intervention type: Drug
intervention name: Pegylated Recombinant Human Endostatin（PEG-ENDO）
description: PEG-ENDO 1 mg/kg or 2 mg/kg or 4 mg/kg or 6 mg/kg or 8 mg/kg+Docetaxel 75 mg/m2，once every 3 weeks at day 1
arm group label: PEG-ENDO+Docetaxel
other name: Docetaxel
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Huang Dingzhi, Ph.D
role: Principal Investigator
affiliation: Tianjin Medical University Cancer Institute & Hospital
last name: Li Lin, Ph.D
role: Principal Investigator
affiliation: Beijing Hospital
last name: Huang Dingzhi, Ph.D
phone: 02223340123
phone ext: 3220
email: dingzhih72@163.com
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Docetaxel
mesh term: Endostatins