<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/NCT02978261</url>
  </required_header>
  <id_info>
    <org_study_id>HMO-PLB1001-I-GBM-01</org_study_id>
    <nct_id>NCT02978261</nct_id>
  </id_info>
  <brief_title>Study of a c-Met Inhibitor PLB1001 in Patients With PTPRZ1-MET Fusion Gene Positive Recurrent High-grade Gliomas</brief_title>
  <official_title>A Phase I, Open-label, Dose Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics (PK) of PLB1001 in Patients With PTPRZ1-MET Fusion Gene Positive Recurrent High-grade Gliomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beijing Pearl Biotechnology Limited Liability Company</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Beijing Pearl Biotechnology Limited Liability Company</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I, open-label, dose-escalation study was conducted to determine the maximum&#xD;
      tolerated dose (MTD), recommended phase II dose (RP2D), dose-limiting toxicities (DLTs),&#xD;
      pharmacokinetics (PK) profile, and preliminary antitumor activity of single and multiple&#xD;
      doses of PLB1001 in Patients with PTPRZ1-MET fusion gene positive recurrent high-grade&#xD;
      Gliomas.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase I, open-label study of PLB1001 administered orally to patients with&#xD;
      PTPRZ1-MET fusion gene positive recurrent high-grade Gliomas. The aim of dose-escalation&#xD;
      study is to estimate the MTD and to identify the dose-limiting toxicity(DLT) and the&#xD;
      recommended phase II dose (RP2D) for PLB1001 single agent as well as to determine the PK/PD&#xD;
      profile. Aprox. 20 patients will be enrolled in this study.&#xD;
&#xD;
      PLB1001 is a potent selective c-Met inhibitor. PLB1001 acts on cancer by blocking abnormal&#xD;
      cMET-mediated signaling (including PTPRZ1-MET fusion gene), leading to profound tumor growth&#xD;
      inhibition in xenografts of PTPRZ1-MET fusion gene positive glioblastoma tumor.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2016</start_date>
  <completion_date type="Actual">December 2018</completion_date>
  <primary_completion_date type="Actual">April 2018</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>Percentage of participants with dose-limiting toxicities</measure>
    <time_frame>2 years</time_frame>
    <description>The primary endpoint is evaluation of safety and tolerability during all the study of therapy following the initiation of single and multiple doses of PLB1001. The safety and tolerability variables to be evaluated in this study are adverse events, vital signs, and electrocardiograms (ECGs), Incidence and nature of DLTs (Dose-Limiting Toxicities), to determine the MTD (Maximum Tolerated Dose).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration versus time curve (AUC) of PLB1001 and its metabolite</measure>
    <time_frame>Day 1-3 Single Dose and Day 1-28 Steady State</time_frame>
    <description>In the study of single-dose, full Pharmacokinetics(PK) profiles of PLB1001 will be obtained following administration of a single oral dose of PLB1001 on Day 1 to Day 2. At multiple-dose, Pharmacokinetics(PK) sampling will include a pre-dose and at the 0.5, 1, 2, 4, 6, 8, 10, 12, 14 and 16 hour time points on days 1and 15 of dosing in the first 28-Day cycle of therapy, and pre-dose on days 2, 16 and 17 of the first 28-Day cycle of therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum plasma concentration observed (Cmax) of PLB1001 and its metabolite</measure>
    <time_frame>Day 1-3 Single Dose and Day 1-28 Steady State</time_frame>
    <description>In the study of single-dose, full Pharmacokinetics(PK) profiles of PLB1001 will be obtained following administration of a single oral dose of PLB1001 on Day 1 to Day 2. At multiple-dose, Pharmacokinetics(PK) sampling will include a pre-dose and at the 0.5, 1, 2, 4, 6, 8, 10, 12, 14 and 16 hour time points on days 1and 15 of dosing in the first 28-Day cycle of therapy, and pre-dose on days 2, 16 and 17 of the first 28-Day cycle of therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Cmax (Tmax) of PLB1001 and its metabolite</measure>
    <time_frame>Day 1-3 Single Dose and Day 1-28 Steady State</time_frame>
    <description>In the study of single-dose, full Pharmacokinetics(PK) profiles of PLB1001 will be obtained following administration of a single oral dose of PLB1001 on Day 1 to Day 2. At multiple-dose, Pharmacokinetics(PK) sampling will include a pre-dose and at the 0.5, 1, 2, 4, 6, 8, 10, 12, 14 and 16 hour time points on days 1and 15 of dosing in the first 28-Day cycle of therapy, and pre-dose on days 2, 16 and 17 of the first 28-Day cycle of therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preliminary antitumor activity of PLB1001</measure>
    <time_frame>2 years</time_frame>
    <description>Preliminary antitumor activity of PLB1001 assessed using RANO</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Glioma</condition>
  <arm_group>
    <arm_group_label>PLB1001</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>There are 4 dose cohorts, including 50mg BID,100mg BID, 200mg BID and 300mg BID in the dose escalation stage and PLB1001 will be administered orally to patients twice daily for each dose cohort.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PLB1001</intervention_name>
    <description>PLB1001 is a capsule in the form of 25 mg and 100mg, twice daily.</description>
    <arm_group_label>PLB1001</arm_group_label>
    <other_name>Bozitinib</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed Informed Consent Form&#xD;
&#xD;
          -  Age≥18 years&#xD;
&#xD;
          -  Histologically or cytologically confirmed recurrent high-grade glioma after concurrent&#xD;
             or adjuvant chemoradiotherapy&#xD;
&#xD;
          -  Prior treatment with temozolomide&#xD;
&#xD;
          -  Must have evidence of PTPRZ1-MET fusion gene positivity from the results of molecular&#xD;
             pre-screening evaluations&#xD;
&#xD;
          -  At least one measurable lesion as per RANO&#xD;
&#xD;
          -  No evidence of recent haemorrhage on baseline MRI of the brain&#xD;
&#xD;
          -  Stable or decreasing dose of corticosteroids within 5 days prior to the first dose&#xD;
&#xD;
          -  Major surgery within 4 weeks prior to first dose of PLB1001&#xD;
&#xD;
          -  Previous anti-cancer and investigational agents within 4 weeks before first dose of&#xD;
             PLB1001. If previous treatment is a monoclonal antibody, then the treatment must be&#xD;
             discontinued at least 6 weeks before first dose of PLB1001&#xD;
&#xD;
          -  Pregnant or nursing women&#xD;
&#xD;
          -  Involved in other clinical trials &lt;30 days prior to first dose&#xD;
&#xD;
          -  Prior therapy with gamma knife or other focal high-dose radiotherapy is allowed, but&#xD;
             the patient must have subsequent histologic documentation of recurrence, unless the&#xD;
             recurrence is a new lesion outside the irradiated field&#xD;
&#xD;
          -  Karnofsky performance status ≥ 50%&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous or current treatment with a c-Met inhibitor or HGF-targeting therapy&#xD;
&#xD;
          -  The subject is unable to undergo MRI scan (e.g. has pacemaker)&#xD;
&#xD;
          -  Clinically significant, uncontrolled heart diseases： Unstable angina; History of&#xD;
             documented congestive heart failure (New York Heart Association functional&#xD;
             classification&gt; II); Uncontrolled hypertension defined by a Systolic Blood Pressure&#xD;
             (SBP) ≥ 145 mm Hg and/or Diastolic Blood Pressure (DBP) ≥85 mm Hg; Arrhythmias.&#xD;
&#xD;
          -  Active peptic ulcer disease or gastritis&#xD;
&#xD;
          -  Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤ 1,&#xD;
             except for alopecia&#xD;
&#xD;
          -  Major surgery within 4 weeks prior to first dose of PLB1001&#xD;
&#xD;
          -  Previous anti-cancer and investigational agents within 4 weeks before first dose of&#xD;
             PLB1001. If previous treatment is a monoclonal antibody, then the treatment must be&#xD;
             discontinued at least 6 weeks before first dose of PLB1001&#xD;
&#xD;
          -  Pregnant or nursing women&#xD;
&#xD;
          -  Involved in other clinical trials &lt;30 days prior to first dose&#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, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beijing Shijitan Hospital, CMU</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beijing Shijitan Hospital,CMU</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100038</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>November 28, 2016</study_first_submitted>
  <study_first_submitted_qc>November 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 30, 2016</study_first_posted>
  <last_update_submitted>March 2, 2020</last_update_submitted>
  <last_update_submitted_qc>March 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02978261
org study id: HMO-PLB1001-I-GBM-01
nct id: NCT02978261
lead sponsor: 
has dmc: No
This phase I, open-label, dose-escalation study was conducted to determine the maximum
      tolerated dose (MTD), recommended phase II dose (RP2D), dose-limiting toxicities (DLTs),
      pharmacokinetics (PK) profile, and preliminary antitumor activity of single and multiple
      doses of PLB1001 in Patients with PTPRZ1-MET fusion gene positive recurrent high-grade
      Gliomas.
This is a Phase I, open-label study of PLB1001 administered orally to patients with
      PTPRZ1-MET fusion gene positive recurrent high-grade Gliomas. The aim of dose-escalation
      study is to estimate the MTD and to identify the dose-limiting toxicity(DLT) and the
      recommended phase II dose (RP2D) for PLB1001 single agent as well as to determine the PK/PD
      profile. Aprox. 20 patients will be enrolled in this study.

      PLB1001 is a potent selective c-Met inhibitor. PLB1001 acts on cancer by blocking abnormal
      cMET-mediated signaling (including PTPRZ1-MET fusion gene), leading to profound tumor growth
      inhibition in xenografts of PTPRZ1-MET fusion gene positive glioblastoma tumor.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of participants with dose-limiting toxicities
time frame: 2 years
description: The primary endpoint is evaluation of safety and tolerability during all the study of therapy following the initiation of single and multiple doses of PLB1001. The safety and tolerability variables to be evaluated in this study are adverse events, vital signs, and electrocardiograms (ECGs), Incidence and nature of DLTs (Dose-Limiting Toxicities), to determine the MTD (Maximum Tolerated Dose).
measure: Area under the plasma concentration versus time curve (AUC) of PLB1001 and its metabolite
time frame: Day 1-3 Single Dose and Day 1-28 Steady State
description: In the study of single-dose, full Pharmacokinetics(PK) profiles of PLB1001 will be obtained following administration of a single oral dose of PLB1001 on Day 1 to Day 2. At multiple-dose, Pharmacokinetics(PK) sampling will include a pre-dose and at the 0.5, 1, 2, 4, 6, 8, 10, 12, 14 and 16 hour time points on days 1and 15 of dosing in the first 28-Day cycle of therapy, and pre-dose on days 2, 16 and 17 of the first 28-Day cycle of therapy
measure: Maximum plasma concentration observed (Cmax) of PLB1001 and its metabolite
time frame: Day 1-3 Single Dose and Day 1-28 Steady State
description: In the study of single-dose, full Pharmacokinetics(PK) profiles of PLB1001 will be obtained following administration of a single oral dose of PLB1001 on Day 1 to Day 2. At multiple-dose, Pharmacokinetics(PK) sampling will include a pre-dose and at the 0.5, 1, 2, 4, 6, 8, 10, 12, 14 and 16 hour time points on days 1and 15 of dosing in the first 28-Day cycle of therapy, and pre-dose on days 2, 16 and 17 of the first 28-Day cycle of therapy
measure: Time to Cmax (Tmax) of PLB1001 and its metabolite
time frame: Day 1-3 Single Dose and Day 1-28 Steady State
description: In the study of single-dose, full Pharmacokinetics(PK) profiles of PLB1001 will be obtained following administration of a single oral dose of PLB1001 on Day 1 to Day 2. At multiple-dose, Pharmacokinetics(PK) sampling will include a pre-dose and at the 0.5, 1, 2, 4, 6, 8, 10, 12, 14 and 16 hour time points on days 1and 15 of dosing in the first 28-Day cycle of therapy, and pre-dose on days 2, 16 and 17 of the first 28-Day cycle of therapy
measure: Preliminary antitumor activity of PLB1001
time frame: 2 years
description: Preliminary antitumor activity of PLB1001 assessed using RANO
arm group label: PLB1001
arm group type: Experimental
description: There are 4 dose cohorts, including 50mg BID,100mg BID, 200mg BID and 300mg BID in the dose escalation stage and PLB1001 will be administered orally to patients twice daily for each dose cohort.
intervention type: Drug
intervention name: PLB1001
description: PLB1001 is a capsule in the form of 25 mg and 100mg, twice daily.
arm group label: PLB1001
other name: Bozitinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Wenbin Li, MD
role: Principal Investigator
affiliation: Beijing Shijitan Hospital, CMU
facility: 
country: China
responsible party type: Sponsor
mesh term: Glioma
sharing ipd: Undecided