<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/NCT03228186</url>
  </required_header>
  <id_info>
    <org_study_id>UMCC 2017.063</org_study_id>
    <secondary_id>HUM00131436</secondary_id>
    <nct_id>NCT03228186</nct_id>
  </id_info>
  <brief_title>Trial of Pevonedistat Plus Docetaxel in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer</brief_title>
  <official_title>Phase II Trial of Pevonedistat (TAK-924) Plus Docetaxel in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan Rogel Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Michigan Rogel Cancer Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is a single institution Phase II single arm trial to assess the efficacy of the&#xD;
      combination of pevonedistat plus docetaxel in patients with previously treated advanced NSCLC&#xD;
      (non-small cell lung cancer).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Pharmaceutical company discontinued the study drug.&#xD;
  </why_stopped>
  <start_date type="Actual">March 5, 2018</start_date>
  <completion_date type="Actual">November 4, 2021</completion_date>
  <primary_completion_date type="Actual">November 4, 2021</primary_completion_date>
  <phase>Phase 2</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>The percentage of patients that respond to treatment</measure>
    <time_frame>Up to 2 Years</time_frame>
    <description>Response is defined as either Partial Response or Complete Response. Partial Response is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions.&#xD;
Complete Response is defined as the disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Median Progression Free Survival Time</measure>
    <time_frame>Up to 2 Years</time_frame>
    <description>Progression-free survival is defined as the duration of time from start of treatment to time of progression.&#xD;
Progressive Disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Overall Survival Time</measure>
    <time_frame>Up to 2 Years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of patients who achieve stable disease</measure>
    <time_frame>Up to 2 Years</time_frame>
    <description>Stable disease rate will be reported as the count and proportion of patients who achieve stable disease.&#xD;
Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for Partial Response (PR) nor sufficient increase to qualify for Progressive Disease (PD), taking as reference the smallest sum LD since the treatment started.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of toxicities by system organ class</measure>
    <time_frame>Up to 30 days post treatment</time_frame>
    <description>All recorded toxicities will be listed and tabulated by system organ class. The NCI CTCAE version 4.03 will be utilized for AE reporting.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Non-small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Pevonedistat plus Docetaxel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pevonedistat 25mg/m2 days 1, 3, 5 Docetaxel 75mg/m2 day 1 21 day cycle</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pevonedistat</intervention_name>
    <description>25mg/m2 days 1, 3, 5</description>
    <arm_group_label>Pevonedistat plus Docetaxel</arm_group_label>
    <other_name>TAK-924</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docetaxel</intervention_name>
    <description>75mg/m2 day 1</description>
    <arm_group_label>Pevonedistat plus Docetaxel</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients 18 years of age or older&#xD;
&#xD;
          -  Histologically confirmed stage IV NSCLC (adenocarcinoma, squamous cell carcinoma,&#xD;
             large cell carcinoma, or not otherwise specified) or recurrent NSCLC not amenable to&#xD;
             curative therapy&#xD;
&#xD;
          -  Patients must have already received platinum-based chemotherapy; they may have also&#xD;
             received prior immunotherapy or targeted therapy&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (an attempt to&#xD;
             quantify cancer patients' general well-being and activities of daily life. The score&#xD;
             ranges from 0 to 5 where 0 is asymptomatic and 5 is death.)&#xD;
&#xD;
          -  Clinical laboratory values within appropriate parameters&#xD;
&#xD;
          -  Female patients who are of childbearing potential and all males must agree to practice&#xD;
             true abstinence or use effective methods of contraception&#xD;
&#xD;
          -  Patients must be able to understand and sign the informed consent.&#xD;
&#xD;
          -  Patients must have measurable disease as defined by RECIST v1.1 criteria&#xD;
&#xD;
          -  It is preferable that patients have an adequate tissue sample available&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Treatment with any investigational products within 4 weeks before the first dose of&#xD;
             any study drug&#xD;
&#xD;
          -  Any serious medical or psychiatric illness that could, in the investigator's opinion,&#xD;
             potentially interfere with the completion of study procedures&#xD;
&#xD;
          -  Active uncontrolled infection or severe infectious disease, such as severe pneumonia,&#xD;
             meningitis, or septicemia that require IV antibiotics within 2 weeks of starting study&#xD;
             treatment&#xD;
&#xD;
          -  Major surgery within 14 days before the first dose of any study drug or a scheduled&#xD;
             surgery during study period&#xD;
&#xD;
          -  Diagnosed or treated for another malignancy within 2 years before randomization or&#xD;
             previously diagnosed with another malignancy and have any evidence of residual&#xD;
             disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are&#xD;
             not excluded if they have undergone resection.&#xD;
&#xD;
          -  Life-threatening illness unrelated to cancer&#xD;
&#xD;
          -  Patients with uncontrolled coagulopathy or bleeding disorder&#xD;
&#xD;
          -  Known human immunodeficiency virus (HIV) seropositivity&#xD;
&#xD;
          -  Known hepatitis B surface antigen seropositivity or known or suspected active&#xD;
             hepatitis C infection&#xD;
&#xD;
          -  Known hepatic cirrhosis or severe pre-existing hepatic impairment&#xD;
&#xD;
          -  Known cardiopulmonary disease&#xD;
&#xD;
          -  Uncontrolled high blood pressure (ie, systolic blood pressure &gt; 180 mm Hg, diastolic&#xD;
             blood pressure &gt; 95 mm Hg)&#xD;
&#xD;
          -  Prolonged rate corrected QT (QTc) interval ≥ 500 msec, calculated according to&#xD;
             institutional guidelines&#xD;
&#xD;
          -  Interstitial lung disease or pulmonary fibrosis&#xD;
&#xD;
          -  Systemic antineoplastic therapy or radiotherapy for other malignant conditions within&#xD;
             14 days before the first dose of any study drug, except for hydroxyurea.&#xD;
&#xD;
          -  Symptomatic or history of untreated brain or leptomeningeal metastases. Treated&#xD;
             patients should be neurologically stable for 4 weeks after completion of appropriate&#xD;
             therapy. Patients should be off steroids at least 3 days prior to start of therapy on&#xD;
             clinical trial.&#xD;
&#xD;
          -  Treatment with clinically significant metabolic enzyme inducers within 14 days before&#xD;
             the first dose of the study drug. Clinically significant metabolic enzyme inducers are&#xD;
             not permitted during this study (see Appendix III for more details).&#xD;
&#xD;
          -  Female patients who are lactating, breastfeeding, or have a positive pregnancy test&#xD;
&#xD;
          -  Female patients who intend to donate eggs (ova) during the course of this study or 4&#xD;
             months after receiving their last dose of study drug(s).&#xD;
&#xD;
          -  Male patients who intend to donate sperm during the course of this study or 4 months&#xD;
             after receiving their last dose of study drug(s).&#xD;
&#xD;
          -  Known hypersensitivity to docetaxel or other drugs formulated with polysorbate 80&#xD;
&#xD;
          -  Prior therapy with docetaxel for non-small cell lung cancer&#xD;
&#xD;
          -  Peripheral neuropathy of CTCAE v4.03 grade ≥ 2&#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>Gregory Kalemkerian, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan Rogel Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Michigan Comprehensive Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48187</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>July 21, 2017</study_first_submitted>
  <study_first_submitted_qc>July 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2017</study_first_posted>
  <last_update_submitted>December 16, 2021</last_update_submitted>
  <last_update_submitted_qc>December 16, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 10, 2022</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>Lung 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>Pevonedistat</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>December 12, 2022</submitted>
    <returned>December 30, 2022</returned>
    <submitted>February 13, 2023</submitted>
    <returned>March 13, 2023</returned>
    <submitted>June 1, 2023</submitted>
    <returned>June 23, 2023</returned>
    <submitted>July 18, 2023</submitted>
    <returned>August 3, 2023</returned>
    <submitted>September 13, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03228186
org study id: UMCC 2017.063
secondary id: HUM00131436
nct id: NCT03228186
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This study is a single institution Phase II single arm trial to assess the efficacy of the
      combination of pevonedistat plus docetaxel in patients with previously treated advanced NSCLC
      (non-small cell lung cancer).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The percentage of patients that respond to treatment
time frame: Up to 2 Years
description: Response is defined as either Partial Response or Complete Response. Partial Response is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions.
Complete Response is defined as the disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions.
measure: Median Progression Free Survival Time
time frame: Up to 2 Years
description: Progression-free survival is defined as the duration of time from start of treatment to time of progression.
Progressive Disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions.
measure: Median Overall Survival Time
time frame: Up to 2 Years
measure: The number of patients who achieve stable disease
time frame: Up to 2 Years
description: Stable disease rate will be reported as the count and proportion of patients who achieve stable disease.
Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for Partial Response (PR) nor sufficient increase to qualify for Progressive Disease (PD), taking as reference the smallest sum LD since the treatment started.
measure: The number of toxicities by system organ class
time frame: Up to 30 days post treatment
description: All recorded toxicities will be listed and tabulated by system organ class. The NCI CTCAE version 4.03 will be utilized for AE reporting.
arm group label: Pevonedistat plus Docetaxel
arm group type: Experimental
description: Pevonedistat 25mg/m2 days 1, 3, 5 Docetaxel 75mg/m2 day 1 21 day cycle
intervention type: Drug
intervention name: Pevonedistat
description: 25mg/m2 days 1, 3, 5
arm group label: Pevonedistat plus Docetaxel
other name: TAK-924
intervention type: Drug
intervention name: Docetaxel
description: 75mg/m2 day 1
arm group label: Pevonedistat plus Docetaxel
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gregory Kalemkerian, M.D.
role: Principal Investigator
affiliation: University of Michigan Rogel Cancer Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Docetaxel
mesh term: Pevonedistat
submitted: December 12, 2022
returned: December 30, 2022
submitted: February 13, 2023
returned: March 13, 2023
submitted: June 1, 2023
returned: June 23, 2023
submitted: July 18, 2023
returned: August 3, 2023
submitted: September 13, 2023