<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/NCT01660360</url>
  </required_header>
  <id_info>
    <org_study_id>PMC1101-TAAC01</org_study_id>
    <nct_id>NCT01660360</nct_id>
  </id_info>
  <brief_title>Phase I Trial of Tanibirumab in Advanced or Metastatic Cancer</brief_title>
  <official_title>A Phase I Study of the Safety and Pharmacokinetics of a Fully Human Monoclonal Antibody to the Vascular Endothelial Growth Factor Receptor2 (Tanibirumab) in Patients With Advanced Cancers or Metastatic Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>PharmAbcine</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>PharmAbcine</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to assess the safety, tolerability, and maximum&#xD;
      tolerated dose (MTD) of Tanibirumab in patients with advanced or metastatic cancer who are&#xD;
      refractory or for whom there are no standard therapeutic option.&#xD;
&#xD;
        -  To evaluate the pharmacokinetics of Tanibirumab in such patients&#xD;
&#xD;
        -  To determine a recommended phase II dose (RP2D) of Tanibirumab based on above&#xD;
           assessments&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase I, first-in-human, open-label, non-randomized, dose-escalating study of&#xD;
      Tanibirumab which is a fully human monoclonal antibody to vascular endothelial growth factor&#xD;
      receptor 2 (VEGFR2/KDR). This study will enroll patients with advanced or metastatic cancer&#xD;
      who are refractory or for whom there are no standard therapeutic options. Tanibirumab will be&#xD;
      administered intravenously to such patients over 60 minutes on Day 1, 8, and 15 (subject to&#xD;
      change pending PK and toxicity data). Each treatment cycle will be a minimum of 28 days in&#xD;
      length. The dose escalation study employing a 3 + 3 design is designed to identify the RP2D&#xD;
      which will be based on safety, tolerability and PK of the RP2D. This study is expected to&#xD;
      enroll a total of approximately 18-24 patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2011</start_date>
  <completion_date type="Actual">September 2013</completion_date>
  <primary_completion_date type="Actual">September 2013</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>Safety and tolerability</measure>
    <time_frame>28days</time_frame>
    <description>The safety and tolerability of Tanibirumab will be assessed using the following measures: frequency and nature of dose-limiting toxicities (DLTs); nature, severity, and relatedness of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, v4.0; changes in vital signs; and changes in clinical laboratory parameters.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics</measure>
    <time_frame>Cycle 1 : predose, 0.5, 2, 4, 24 and 72 hours after 1st dose, predose and 0.5 hours after 2nd dose, predose, 0.5, 2, 4, 24, 72, 168 and 336 hours after 3rd dose. After cycle 2: predose of 1st dose and 0.5 hour after 3rd dose.</time_frame>
    <description>The following PK parameters will be derived from the serum concentration-time profile of Tanibirumab following administration: serum total exposure (AUC), Cmax, clearance, volume of distribution (central compartment Vc and at steady state Vss), and half-life (t½).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy</measure>
    <time_frame>completion of 2 and more cycle</time_frame>
    <description>The following activity outcome measures will be assessed: objective response, defined as a complete or partial response confirmed 4 weeks after initial documentation; duration of objective response; and progression-free survival. Objective response and disease progression will be determined using RECIST 1.1</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Advanced Cancer</condition>
  <condition>Metastatic Cancer</condition>
  <arm_group>
    <arm_group_label>Tanibirumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The total dose of Tanibirumab for each patient will depend on dose level assignment and the patient's weight. Dose levels to be potentially tested in Phase I include: 1 mg/kg, 2 mg/kg, 4 mg/kg, 8 mg/kg, 12 mg/kg, 16 mg/kg, and 20 mg/kg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Tanibirumab</intervention_name>
    <arm_group_label>Tanibirumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; 20 years&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
          -  Histologically documented, incurable, locally advanced or metastatic cancers that have&#xD;
             failed to respond to at least one prior regimen or for which there is no standard&#xD;
             therapy.&#xD;
&#xD;
          -  Disease that is measurable or evaluable by RECIST 1.1 criteria (for Solid Tumors)&#xD;
&#xD;
          -  ECOG performance status 0-2&#xD;
&#xD;
          -  Documented negative pregnancy test for women of childbearing potential and use of an&#xD;
             effective means of contraception for both men and women while enrolled in the study&#xD;
&#xD;
          -  Granulocyte count ≥ 1,500/㎣, platelet count ≥ 100,000/㎣, and hemoglobin ≥ 9 g/dL&#xD;
&#xD;
          -  Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)(≤ 3 x ULN if liver metastatic&#xD;
             cancer)&#xD;
&#xD;
          -  Alkline phosphatase, AST and ALT ≤ 2.5 x ULN (≤ 5 x ULN if liver metastatic cancer)&#xD;
&#xD;
          -  Serum creatinine ≤ 1.5 mg/dL&#xD;
&#xD;
          -  INR (international normalized ratio) ≤ 1.3, and aPTT (activated partial thromboplastin&#xD;
             time) ≤ 1.5 x ULN&#xD;
&#xD;
          -  Subject had to have a projected life expectancy of at least 3 months&#xD;
&#xD;
          -  Bazetts correction QTc &lt; 450 msec in ECG at Screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Less than 4 weeks since last chemotherapy (including biologic unless previous Avastin&#xD;
             treatment, experimental, and hormonal therapy), radiation therapy, or major surgical&#xD;
             procedure&#xD;
&#xD;
          -  All incisions from any procedure must be fully healed and sutures removed prior to&#xD;
             infusion on Day 1&#xD;
&#xD;
          -  Pleural effusions, ascites, or leptomeningeal disease as the only manifestation of the&#xD;
             current malignancy&#xD;
&#xD;
          -  Subjects that have hypertension that is remained uncontrolled, despite drug regimen.&#xD;
&#xD;
          -  Subjects with grade III or IV hemorrhage/bleeding and who have experienced pulmonary&#xD;
             hemorrhage/hemoptysis (exceed size of 2.5 mL of erythrocyte) or who have experienced&#xD;
             grade III/IV hemorrhage/bleeding.&#xD;
&#xD;
          -  The presence of gastrointestinal perforation&#xD;
&#xD;
          -  The presence of tracheoesophageal fistula or grade Ⅳ fistula&#xD;
&#xD;
          -  Subjects with grade Ⅳ proteinuria (nephritic syndrome)&#xD;
&#xD;
          -  The presence of arterial thromboembolic events&#xD;
&#xD;
          -  Subjects who have history of life threatening (grade Ⅳ) pulmonary embolism&#xD;
&#xD;
          -  Subjects with a known hypersensitivity to CHO cell product or other recombined human&#xD;
             or humanized antibody&#xD;
&#xD;
          -  Subjects with mental illness&#xD;
&#xD;
          -  Subjects with a known hypersensitivity to any of the ingredients/substrates in&#xD;
             investigational product of this study&#xD;
&#xD;
          -  Subjects who given any investigational drug within longer period between 30 days and 5&#xD;
             times of half life before participation in this study&#xD;
&#xD;
          -  Active infection requiring IV antibiotics&#xD;
&#xD;
          -  Active autoimmune disease that is not controlled by drugs&#xD;
&#xD;
          -  Clinically important history of liver disease, including viral or other active&#xD;
             hepatitis, current alcohol abuse, or cirrhosis&#xD;
&#xD;
          -  Known human immunodeficiency virus (HIV) infection&#xD;
&#xD;
          -  Any other diseases, metabolic dysfunction, physical examination finding, or clinical&#xD;
             laboratory finding giving reasonable suspicion of a disease or condition that&#xD;
             contraindicates the use of an investigational drug or that may affect the&#xD;
             interpretation of the results or renders the subjects at high risk from treatment&#xD;
             complications&#xD;
&#xD;
          -  Significant traumatic injury within 3 weeks of Day 1&#xD;
&#xD;
          -  Inability to comply with study and follow-up procedures&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Young Seok Park, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Samsung Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>135-230</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>January 2014</verification_date>
  <study_first_submitted>August 6, 2012</study_first_submitted>
  <study_first_submitted_qc>August 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 8, 2012</study_first_posted>
  <last_update_submitted>January 27, 2014</last_update_submitted>
  <last_update_submitted_qc>January 27, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 29, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Tanibirumab Phase I trial</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Neoplasms, Second Primary</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/NCT01660360
org study id: PMC1101-TAAC01
nct id: NCT01660360
lead sponsor: 
has dmc: No
The primary objective of this study is to assess the safety, tolerability, and maximum
      tolerated dose (MTD) of Tanibirumab in patients with advanced or metastatic cancer who are
      refractory or for whom there are no standard therapeutic option.

        -  To evaluate the pharmacokinetics of Tanibirumab in such patients

        -  To determine a recommended phase II dose (RP2D) of Tanibirumab based on above
           assessments
This is a Phase I, first-in-human, open-label, non-randomized, dose-escalating study of
      Tanibirumab which is a fully human monoclonal antibody to vascular endothelial growth factor
      receptor 2 (VEGFR2/KDR). This study will enroll patients with advanced or metastatic cancer
      who are refractory or for whom there are no standard therapeutic options. Tanibirumab will be
      administered intravenously to such patients over 60 minutes on Day 1, 8, and 15 (subject to
      change pending PK and toxicity data). Each treatment cycle will be a minimum of 28 days in
      length. The dose escalation study employing a 3 + 3 design is designed to identify the RP2D
      which will be based on safety, tolerability and PK of the RP2D. This study is expected to
      enroll a total of approximately 18-24 patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and tolerability
time frame: 28days
description: The safety and tolerability of Tanibirumab will be assessed using the following measures: frequency and nature of dose-limiting toxicities (DLTs); nature, severity, and relatedness of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, v4.0; changes in vital signs; and changes in clinical laboratory parameters.
measure: Pharmacokinetics
time frame: Cycle 1 : predose, 0.5, 2, 4, 24 and 72 hours after 1st dose, predose and 0.5 hours after 2nd dose, predose, 0.5, 2, 4, 24, 72, 168 and 336 hours after 3rd dose. After cycle 2: predose of 1st dose and 0.5 hour after 3rd dose.
description: The following PK parameters will be derived from the serum concentration-time profile of Tanibirumab following administration: serum total exposure (AUC), Cmax, clearance, volume of distribution (central compartment Vc and at steady state Vss), and half-life (t½).
measure: Efficacy
time frame: completion of 2 and more cycle
description: The following activity outcome measures will be assessed: objective response, defined as a complete or partial response confirmed 4 weeks after initial documentation; duration of objective response; and progression-free survival. Objective response and disease progression will be determined using RECIST 1.1
arm group label: Tanibirumab
arm group type: Experimental
description: The total dose of Tanibirumab for each patient will depend on dose level assignment and the patient's weight. Dose levels to be potentially tested in Phase I include: 1 mg/kg, 2 mg/kg, 4 mg/kg, 8 mg/kg, 12 mg/kg, 16 mg/kg, and 20 mg/kg.
intervention type: Biological
intervention name: Tanibirumab
arm group label: Tanibirumab
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Young Seok Park, MD, PhD
role: Principal Investigator
affiliation: Samsung Medical Center
facility: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Neoplasm Metastasis
mesh term: Neoplasms, Second Primary