<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/NCT03246854</url>
  </required_header>
  <id_info>
    <org_study_id>DBPR112-101</org_study_id>
    <nct_id>NCT03246854</nct_id>
  </id_info>
  <brief_title>A Study of DBPR112 in Patients With Head and Neck Cancer and EGFR Mutated Lung Cancer</brief_title>
  <official_title>Phase I, Open-Label, Multiple Dose, Dose-Finding and Expansion Clinical Study to Assess the Safety, Pharmacokinetics, and Efficacy of DBPR112 in Patients With Head and Neck Cancer and EGFR Mutated Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Health Research Institutes, Taiwan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Health Research Institutes, Taiwan</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study is being performed to assess the MTD, pharmacokinetics (PK), safety, tolerability&#xD;
      and preliminary antitumor activity of DBPR112 in patients with head and neck cancer and EGFR&#xD;
      mutated lung cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase I, multi-center, open-label, first-in-human study to determine the MTD and&#xD;
      RP2D of DBPR112 and to assess the safety, tolerability and PK of DBPR112 in Asian patients.&#xD;
      Patients with non-small cell cancer (NSCLC) who have progressed following prior therapy with&#xD;
      an epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor or in patients with&#xD;
      squamous cell cancer of head and neck (SCCHN) who have progressed following prior standard&#xD;
      therapy will be selected. Approximately 24 to 30 patients will be enrolled in this study as&#xD;
      out patients/inpatients, in 2 study centers in Taiwan.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    No more funding&#xD;
  </why_stopped>
  <start_date type="Actual">July 18, 2017</start_date>
  <completion_date type="Actual">August 4, 2018</completion_date>
  <primary_completion_date type="Actual">August 4, 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>Maximum Tolerated Dose (MTD)</measure>
    <time_frame>up to 22 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve (AUC from 0 to infinity)</measure>
    <time_frame>For Cycle 1 (each cycle is 28 days) and Cycle 2, Day 1, predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8 and 24 hrs (i.e. predose on Day 2).Predose samples on Cycle 1 Days 8, 15, 22, and 28, Cycle 2 Day 15, and Cycle3-6 Days 1 and 15.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Observed Maximum Plasma Concentration (Cmax)</measure>
    <time_frame>For Cycle 1 (each cycle is 28 days) and Cycle 2, Day 1, predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8 and 24 hrs (i.e. predose on Day 2).Predose samples on Cycle 1 Days 8, 15, 22, and 28, Cycle 2 Day 15, and Cycle3-6 Days 1 and 15.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time of Maximum Plasma Concentration (tmax)</measure>
    <time_frame>For Cycle 1 (each cycle is 28 days) and Cycle 2, Day 1, predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8 and 24 hrs (i.e. predose on Day 2).Predose samples on Cycle 1 Days 8, 15, 22, and 28, Cycle 2 Day 15, and Cycle3-6 Days 1 and 15.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence and intensity of Adverse Events and Serious Adverse Events as a measure of safety</measure>
    <time_frame>Adverse events were collected from the time of the first dose of investigational product until 30 days after the last dose of investigational product administration.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preliminary antitumor activity of DBPR112 in patients with solid tumors</measure>
    <time_frame>The tumor responses were collected from the time of the first dose of investigational product until 30 days after the last dose of investigational product administration.</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Head and Neck Cancer</condition>
  <condition>NSCLC</condition>
  <arm_group>
    <arm_group_label>DBPR112</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DBPR112</intervention_name>
    <description>DBPR112 hard gelatin capsule solid dosage formulation; strength: 25 mg, 100 mg.</description>
    <arm_group_label>DBPR112</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female patients&#xD;
&#xD;
          -  Age from ≥18 to ≤70 years&#xD;
&#xD;
          -  Life expectancy &gt;12 weeks per investigator's judgement&#xD;
&#xD;
          -  Squamous cell carcinoma of head and neck that has failed prior standard therapy for&#xD;
             metastatic disease or advanced EGFR-mutated NSCLC that has failed prior standard&#xD;
             therapy including at least one anti EGFR TK inhibitor&#xD;
&#xD;
          -  Non-measurable but evaluable disease, or measurable disease per RECIST 1.1&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          -  Adequate blood and organ function&#xD;
&#xD;
          -  Male and female patients must agree to use contraception while on study and for 90&#xD;
             days after the last dose of DBPR112&#xD;
&#xD;
          -  Aspartate aminotransferase/ALT &lt;3 X ULN if no metastasis, and AST/ALT &lt;5 X ULN in&#xD;
             presence of metastasis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of allergic reactions to any component of DBPR112&#xD;
&#xD;
          -  History of unstable central nervous system (CNS) metastases or seizure disorder&#xD;
             related to the malignancy; however, those patients who were treated for prior CNS&#xD;
             metastases and who are asymptomatic may participate in the study&#xD;
&#xD;
          -  History of congestive heart failure, unstable angina pectoris, unstable atrial&#xD;
             fibrillation, or cardiac arrhythmia&#xD;
&#xD;
          -  Exposure to any other investigational or commercial anticancer agents or therapies&#xD;
             administered with the intention to treat malignancy within 28 days for&#xD;
             chemotherapeutics and targeted agents, or 5 half-lives for proteins, whichever is&#xD;
             longer, before the first dose of DBPR112&#xD;
&#xD;
          -  Significant surgical intervention within 21 days of the first dose of DBPR112 or with&#xD;
             ongoing postoperative complications&#xD;
&#xD;
          -  Chronic skin condition that requires prescribed oral or intravenous treatment&#xD;
&#xD;
          -  History of severe rash that required discontinuation of prior EGFR targeted therapy&#xD;
&#xD;
          -  History of interstitial lung disease or non-infectious pneumonitis except for those&#xD;
             induced by radiation therapy&#xD;
&#xD;
          -  Toxicities from any prior therapy, surgery, or radiotherapy must have resolved to&#xD;
             Grade 0 or 1 as per the National Cancer Institute (NCI) - Common Terminology Criteria&#xD;
             for Adverse Events (CTCAE) Version 4.03 or equivalent&#xD;
&#xD;
          -  Insufficient organ function as indicated by the following parameters&#xD;
&#xD;
               1. Absolute neutrophil count (ANC) &lt;1,500 /µL&#xD;
&#xD;
               2. Platelets &lt;100,000 /µL&#xD;
&#xD;
               3. Hemoglobin &lt;10 g/dL&#xD;
&#xD;
               4. Serum creatinine &gt;1.5 X ULN&#xD;
&#xD;
               5. Serum total bilirubin &gt;1.5 X ULN&#xD;
&#xD;
               6. Aspartate aminotransferase/ALT &gt;3 X ULN if no metastasis, AST/ALT &gt;5 X ULN in&#xD;
                  presence of metastasis&#xD;
&#xD;
               7. International normalized ratio or prothrombin time &gt;1.5 X ULN&#xD;
&#xD;
          -  Known history of human immunodeficiency virus (HIV)1 or 2&#xD;
&#xD;
          -  Active clinically significant infection requiring systemic therapy&#xD;
&#xD;
          -  Positive test for hepatitis B (HBsAg) or hepatitis C (anti-HCV antibody)&#xD;
&#xD;
          -  Child-Pugh B &amp; C stage liver disease or liver function impairment&#xD;
&#xD;
          -  Underlying medical conditions that, in the Investigator's opinion, will make the&#xD;
             administration of DBPR112 hazardous or obscure the interpretation of toxicity or AEs&#xD;
&#xD;
          -  Inability to swallow oral medications (capsules and tablets) without chewing,&#xD;
             breaking, crushing, opening or otherwise altering the product formulation. Patients&#xD;
             should not have gastrointestinal illnesses that would preclude the absorption of&#xD;
             DBPR112, which is an oral agent&#xD;
&#xD;
          -  Judgment by the investigator that the patient should not participate in the study if&#xD;
             the patient is unlikely to comply with study procedures, restrictions and requirements&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>10048</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Medical University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>110</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>July 7, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2017</study_first_posted>
  <last_update_submitted>December 15, 2020</last_update_submitted>
  <last_update_submitted_qc>December 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>DBPR112</keyword>
  <keyword>EGFR mutated NSCLC</keyword>
  <keyword>squamous cell cancer of head and neck</keyword>
  <keyword>maximum tolerated dose</keyword>
  <keyword>recommended Phase 2 dose</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Head and Neck Neoplasms</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/NCT03246854
org study id: DBPR112-101
nct id: NCT03246854
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
The study is being performed to assess the MTD, pharmacokinetics (PK), safety, tolerability
      and preliminary antitumor activity of DBPR112 in patients with head and neck cancer and EGFR
      mutated lung cancer.
This is a Phase I, multi-center, open-label, first-in-human study to determine the MTD and
      RP2D of DBPR112 and to assess the safety, tolerability and PK of DBPR112 in Asian patients.
      Patients with non-small cell cancer (NSCLC) who have progressed following prior therapy with
      an epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor or in patients with
      squamous cell cancer of head and neck (SCCHN) who have progressed following prior standard
      therapy will be selected. Approximately 24 to 30 patients will be enrolled in this study as
      out patients/inpatients, in 2 study centers in Taiwan.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD)
time frame: up to 22 months
measure: Area Under the Plasma Concentration-Time Curve (AUC from 0 to infinity)
time frame: For Cycle 1 (each cycle is 28 days) and Cycle 2, Day 1, predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8 and 24 hrs (i.e. predose on Day 2).Predose samples on Cycle 1 Days 8, 15, 22, and 28, Cycle 2 Day 15, and Cycle3-6 Days 1 and 15.
measure: Observed Maximum Plasma Concentration (Cmax)
time frame: For Cycle 1 (each cycle is 28 days) and Cycle 2, Day 1, predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8 and 24 hrs (i.e. predose on Day 2).Predose samples on Cycle 1 Days 8, 15, 22, and 28, Cycle 2 Day 15, and Cycle3-6 Days 1 and 15.
measure: Time of Maximum Plasma Concentration (tmax)
time frame: For Cycle 1 (each cycle is 28 days) and Cycle 2, Day 1, predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8 and 24 hrs (i.e. predose on Day 2).Predose samples on Cycle 1 Days 8, 15, 22, and 28, Cycle 2 Day 15, and Cycle3-6 Days 1 and 15.
measure: Incidence and intensity of Adverse Events and Serious Adverse Events as a measure of safety
time frame: Adverse events were collected from the time of the first dose of investigational product until 30 days after the last dose of investigational product administration.
measure: Preliminary antitumor activity of DBPR112 in patients with solid tumors
time frame: The tumor responses were collected from the time of the first dose of investigational product until 30 days after the last dose of investigational product administration.
arm group label: DBPR112
arm group type: Experimental
intervention type: Drug
intervention name: DBPR112
description: DBPR112 hard gelatin capsule solid dosage formulation; strength: 25 mg, 100 mg.
arm group label: DBPR112
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Head and Neck Neoplasms