<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/NCT04402008</url>
  </required_header>
  <id_info>
    <org_study_id>SPI-POZ-104</org_study_id>
    <nct_id>NCT04402008</nct_id>
  </id_info>
  <brief_title>Study of Poziotinib in Japanese Patients With NSCLC</brief_title>
  <official_title>A Phase 1/2 Dose Finding Study of Poziotinib in Japanese Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Spectrum Pharmaceuticals, Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Spectrum Pharmaceuticals, Inc</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A Phase 1/2, open-label, multicenter study to determine dose, tolerability, safety and&#xD;
      efficacy of poziotinib in Japanese patients non-small cell lung cancer (NSCLC).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 1/2, open-label, multicenter study in Japanese patients with locally advanced&#xD;
      or metastatic NSCLC. This study will be conducted in two parts. Phase 1 is designed to&#xD;
      observe the maximum tolerated dose (MTD) or maximum administered dose (MAD) of poziotinib&#xD;
      when administered once daily or twice daily. Phase 2 will evaluate the safety and efficacy of&#xD;
      the dose determined in Phase 1. Study participation includes a 30 day screening period, up to&#xD;
      24 months of treatment, and long-term follow-up for a maximum of 24 months after&#xD;
      discontinuation of study treatment.&#xD;
&#xD;
      Phase 1 will enroll up to 36 patients into a dose finding study with two parallel, randomized&#xD;
      dose groups. Each group will undergo a dose-finding scheme using a 3+3 design with the&#xD;
      assessment of dose-limiting toxicities (DLTs) at up to three dose levels. Patients will be&#xD;
      randomized into once daily (QD) or twice daily (BID) dose groups. The DLT assessment will be&#xD;
      conducted in the first cycle of treatment and therefore, poziotinib dose modifications are&#xD;
      not permitted during this cycle. Patients will be hospitalized for the first 2 weeks.&#xD;
&#xD;
      Phase 2 will enroll 40 additional NSCLC patients with EGFR (20 patients) or HER2 (20&#xD;
      patients) exon 20 insertion mutations. Efficacy and safety of the dose and dosing regimen&#xD;
      determined in Phase 1 will be evaluated. All patients will be treated in 28-day cycles for up&#xD;
      to 24 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Business decision, not related to safety.&#xD;
  </why_stopped>
  <start_date type="Actual">June 26, 2020</start_date>
  <completion_date type="Actual">May 15, 2023</completion_date>
  <primary_completion_date type="Actual">February 15, 2023</primary_completion_date>
  <phase>Phase 1/Phase 2</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>
    <intervention_model_description>Phase 1 will have two randomized, parallel dose groups comparing daily dosing and twice daily dosing at 3 dose levels.&#xD;
Phase 2 will be a single dose group evaluating the safety and efficacy of the dose determined in Phase 1 in 2 Cohorts. Cohort 1: EGFR exon 20 insertion mutations and Cohort 2: HER2 exon 20 insertion mutations.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase 1: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD)</measure>
    <time_frame>28 Days</time_frame>
    <description>MTD/MAD will be assessed based on the occurrence of defined dose-limiting toxicities (DLT) and all available safety information during first cycle of treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 2: Objective Response Rate (ORR)</measure>
    <time_frame>24 months</time_frame>
    <description>The proportion of patients who achieve Complete Response (CR) or Partial response (PR) by the best response from the first dose of poziotinib to the end of the study.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Disease Control Rate (DCR)</measure>
    <time_frame>24 months</time_frame>
    <description>The proportion of patients who achieve CR, PR, and Stable Disease (SD) by the best response from the first dose of poziotinib to the end of the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Duration of Response (DoR)</measure>
    <time_frame>24 months</time_frame>
    <description>The number of days from the date that measurement criteria are first met for CR or PR (whichever status is recorded first) until the first subsequent date that progressive disease or death is documented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Progression Free Survival (PFS)</measure>
    <time_frame>24 months</time_frame>
    <description>The number of days from the treatment start date to the date of documented disease progression or death.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Phase 2: Exploratory - Overall Survival</measure>
    <time_frame>2 years</time_frame>
    <description>The number of days from the treatment start date to the date of death due to any cause.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">42</enrollment>
  <condition>NSCLC</condition>
  <arm_group>
    <arm_group_label>Phase 1: Once Daily Dosing</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose finding at 8 mg, 12 mg, or 16 mg of poziotinib once daily in 28-day treatment cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1: Twice Daily Dosing</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose finding at 4 mg, 6 mg, or 8 mg of poziotinib twice daily in 28-day treatment cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2: Once Daily Dosing or Twice Daily Dosing</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Once Daily or Twice Daily Dosing as determined in Phase 1 in 28-day treatment cycles.&#xD;
Cohort 1: EGFR exon 20 insertion mutations&#xD;
Cohort 2: HER2 exon 20 insertion mutations</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Poziotinib Once Daily Dosing</intervention_name>
    <description>The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.</description>
    <arm_group_label>Phase 1: Once Daily Dosing</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Poziotinib Twice Daily Dosing</intervention_name>
    <description>The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.</description>
    <arm_group_label>Phase 1: Twice Daily Dosing</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Poziotinib Once Daily Dosing or Twice Daily Dosing as determined in Phase 1</intervention_name>
    <description>The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.</description>
    <arm_group_label>Phase 2: Once Daily Dosing or Twice Daily Dosing</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Patient must be willing and capable of giving written Informed Consent, adhering to&#xD;
             dosing and visit schedules, and meeting all study requirements&#xD;
&#xD;
          -  Previously treated patient with histologically or cytologically confirmed (archival&#xD;
             tissue accepted) locally advanced or metastatic non-small cell lung cancer (NSCLC) and&#xD;
             is not a candidate for definitive therapy&#xD;
&#xD;
               -  Phase 1: No test for mutational status is required&#xD;
&#xD;
               -  Phase 2: Documented EGFR or HER2 exon 20 insertion mutations (including&#xD;
                  duplication mutations) in NSCLC patients&#xD;
&#xD;
          -  Prior treatment status:&#xD;
&#xD;
               -  Phase 1: Patient with refractory NSCLC to available standard therapies&#xD;
&#xD;
               -  Phase 2: Progression after at least one systemic therapy for locally advanced or&#xD;
                  metastatic disease&#xD;
&#xD;
          -  Patient has measurable NSCLC disease, as per the Response Evaluation Criteria in Solid&#xD;
             Tumors (RECIST, version 1.1). Metastatic lesions in bone, CNS, or in brain cannot be&#xD;
             used for target lesions.&#xD;
&#xD;
          -  Patient has recovered from prior systemic therapy for metastatic disease to Grade ≤1&#xD;
             for non-hematologic toxicities (except for Grade ≤2 peripheral neuropathy) and has&#xD;
             adequate hematologic, hepatic, and renal function at Baseline&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Patient is concurrently receiving chemotherapy, biologics, immunotherapy for cancer&#xD;
             treatment; systemic anti-cancer treatment or investigational treatment should not be&#xD;
             used within 2 weeks prior to Cycle 1, Day 1; local radiation therapy for bone pain may&#xD;
             be allowed&#xD;
&#xD;
          -  Patient has used strong inhibitors/inducers of CYP3A4 and CYP2D6 within 1 month prior&#xD;
             to Cycle 1, Day 1&#xD;
&#xD;
          -  Patient has had another primary malignancy within 3 years prior to starting study&#xD;
             treatment, except for adequately treated basal or squamous cell carcinoma of the skin&#xD;
             or cancer of the cervix in situ&#xD;
&#xD;
          -  Patient is pregnant or breastfeeding&#xD;
&#xD;
          -  Phase 2 : Patient has had previous treatment with poziotinib. The currently approved&#xD;
             TKIs that are not considered to be exon 20 insertion-selective are permissible&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>National Cancer Center East</name>
      <address>
        <city>Kashiwa</city>
        <state>Chiba</state>
        <zip>277-8577</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Osaka City General Hospital</name>
      <address>
        <city>Miyakojima-ku</city>
        <state>Osaka</state>
        <zip>534-0021</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shizuoka Cancer Center</name>
      <address>
        <city>Sunto District</city>
        <state>Shizuoka</state>
        <zip>411-8777</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>May 21, 2020</study_first_submitted>
  <study_first_submitted_qc>May 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 26, 2020</study_first_posted>
  <last_update_submitted>July 12, 2023</last_update_submitted>
  <last_update_submitted_qc>July 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>EGFR</keyword>
  <keyword>HER2</keyword>
  <keyword>Exon 20 insertion mutation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_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/NCT04402008
org study id: SPI-POZ-104
nct id: NCT04402008
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
A Phase 1/2, open-label, multicenter study to determine dose, tolerability, safety and
      efficacy of poziotinib in Japanese patients non-small cell lung cancer (NSCLC).
This is a Phase 1/2, open-label, multicenter study in Japanese patients with locally advanced
      or metastatic NSCLC. This study will be conducted in two parts. Phase 1 is designed to
      observe the maximum tolerated dose (MTD) or maximum administered dose (MAD) of poziotinib
      when administered once daily or twice daily. Phase 2 will evaluate the safety and efficacy of
      the dose determined in Phase 1. Study participation includes a 30 day screening period, up to
      24 months of treatment, and long-term follow-up for a maximum of 24 months after
      discontinuation of study treatment.

      Phase 1 will enroll up to 36 patients into a dose finding study with two parallel, randomized
      dose groups. Each group will undergo a dose-finding scheme using a 3+3 design with the
      assessment of dose-limiting toxicities (DLTs) at up to three dose levels. Patients will be
      randomized into once daily (QD) or twice daily (BID) dose groups. The DLT assessment will be
      conducted in the first cycle of treatment and therefore, poziotinib dose modifications are
      not permitted during this cycle. Patients will be hospitalized for the first 2 weeks.

      Phase 2 will enroll 40 additional NSCLC patients with EGFR (20 patients) or HER2 (20
      patients) exon 20 insertion mutations. Efficacy and safety of the dose and dosing regimen
      determined in Phase 1 will be evaluated. All patients will be treated in 28-day cycles for up
      to 24 months.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Phase 1 will have two randomized, parallel dose groups comparing daily dosing and twice daily dosing at 3 dose levels.
Phase 2 will be a single dose group evaluating the safety and efficacy of the dose determined in Phase 1 in 2 Cohorts. Cohort 1: EGFR exon 20 insertion mutations and Cohort 2: HER2 exon 20 insertion mutations.
primary purpose: Treatment
masking: None (Open Label)
measure: Phase 1: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD)
time frame: 28 Days
description: MTD/MAD will be assessed based on the occurrence of defined dose-limiting toxicities (DLT) and all available safety information during first cycle of treatment.
measure: Phase 2: Objective Response Rate (ORR)
time frame: 24 months
description: The proportion of patients who achieve Complete Response (CR) or Partial response (PR) by the best response from the first dose of poziotinib to the end of the study.
measure: Phase 2: Disease Control Rate (DCR)
time frame: 24 months
description: The proportion of patients who achieve CR, PR, and Stable Disease (SD) by the best response from the first dose of poziotinib to the end of the study.
measure: Phase 2: Duration of Response (DoR)
time frame: 24 months
description: The number of days from the date that measurement criteria are first met for CR or PR (whichever status is recorded first) until the first subsequent date that progressive disease or death is documented.
measure: Phase 2: Progression Free Survival (PFS)
time frame: 24 months
description: The number of days from the treatment start date to the date of documented disease progression or death.
measure: Phase 2: Exploratory - Overall Survival
time frame: 2 years
description: The number of days from the treatment start date to the date of death due to any cause.
arm group label: Phase 1: Once Daily Dosing
arm group type: Experimental
description: Dose finding at 8 mg, 12 mg, or 16 mg of poziotinib once daily in 28-day treatment cycles.
arm group label: Phase 1: Twice Daily Dosing
arm group type: Experimental
description: Dose finding at 4 mg, 6 mg, or 8 mg of poziotinib twice daily in 28-day treatment cycles.
arm group label: Phase 2: Once Daily Dosing or Twice Daily Dosing
arm group type: Experimental
description: Once Daily or Twice Daily Dosing as determined in Phase 1 in 28-day treatment cycles.
Cohort 1: EGFR exon 20 insertion mutations
Cohort 2: HER2 exon 20 insertion mutations
intervention type: Drug
intervention name: Poziotinib Once Daily Dosing
description: The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.
arm group label: Phase 1: Once Daily Dosing
intervention type: Drug
intervention name: Poziotinib Twice Daily Dosing
description: The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.
arm group label: Phase 1: Twice Daily Dosing
intervention type: Drug
intervention name: Poziotinib Once Daily Dosing or Twice Daily Dosing as determined in Phase 1
description: The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.
arm group label: Phase 2: Once Daily Dosing or Twice Daily Dosing
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
sharing ipd: No