<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/NCT04467801</url>
  </required_header>
  <id_info>
    <org_study_id>IIT-2019-IpatTax</org_study_id>
    <nct_id>NCT04467801</nct_id>
  </id_info>
  <brief_title>Ipatasertib and Docetaxel in Metastatic NSCLC Patients Who Have Failed 1st Line Immunotherapy</brief_title>
  <acronym>Ipat-Lung</acronym>
  <official_title>A Multi-center Phase II Study of Ipatasertib in Combination With Docetaxel in Metastatic/Advanced NSCLC Patients Who Have Failed or Are Intolerant to 1st Line Immunotherapy (Ipat-Lung)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jun Zhang, MD, PhD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Iowa</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Kentucky</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Kansas Medical 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      For metastatic/advanced NSCLC patients who do not have targetable mutations, either&#xD;
      immunotherapy targeting the programmed death-1 and its ligand (PD-1/L1) pathway alone or in&#xD;
      combination with platinum doublet chemotherapy is now a standard of care. However, still&#xD;
      about half of the patients do not benefit due to treatment resistance. It is therefore&#xD;
      critically important to find novel therapies and combinations to benefit patients who have&#xD;
      failed or are intolerant to 1st line immunotherapy.&#xD;
&#xD;
      This study hypothesizes that ipatasertib in combination with taxane (e.g. docetaxel) can be&#xD;
      an effective strategy. Ipatasertib is a novel adenosine triphosphate (ATP)-competitive&#xD;
      inhibitor that has demonstrated robust and selective targeting of protein kinase B (PKB, also&#xD;
      known as AKT) in cancer patients. Importantly, evidence from preclinical studies has&#xD;
      demonstrated that AKT inhibitors (e.g. ipatasertib) can enhance the therapeutic effect of&#xD;
      chemotherapy as well as immunotherapy via modulating Phosphatidylinositol 3-kinase&#xD;
      (PI3'K)-AKT activity.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 14, 2021</start_date>
  <completion_date type="Anticipated">August 2025</completion_date>
  <primary_completion_date type="Anticipated">August 2023</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>Progression Free Survival</measure>
    <time_frame>up to 12 months</time_frame>
    <description>RECIST 1.1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of adverse events experienced by participants receiving treatment with ipatasertib in combination with docetaxel</measure>
    <time_frame>At cycle 1day 8 (each cycle is 21 days) up to 2 months (60 days) after End of treatment</time_frame>
    <description>CTCAE Version 5.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate</measure>
    <time_frame>every 6 weeks up to 12 months</time_frame>
    <description>RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Cycle 1day 1 (each cycle is 21 days) to up to 12 months after end of treatment</time_frame>
    <description>Medical record</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>NSCLC Stage IV</condition>
  <condition>NSCLC Stage IIIB</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ipatasertib, 400 mg once daily, Oral, Days 1-14 of each 21 day cycle (2 weeks on and 1 week off).&#xD;
Docetaxel, 75 mg/m2, Intra-venous, Day 1 of each 21 day cycle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ipatasertib</intervention_name>
    <description>Ipatasertib is a novel ATP-competitive inhibitor. It is taken by mouth once daily.</description>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ability of participant OR Legally Authorized Representative (LAR) to understand this&#xD;
             study, and participant or LAR willingness to sign a written informed consent&#xD;
&#xD;
          -  Life expectancy ≥12 weeks&#xD;
&#xD;
          -  Males and females age ≥ 18 years&#xD;
&#xD;
          -  Allowable type and amount of prior therapy:&#xD;
&#xD;
        First line anti-Programmed death receptor and ligand (PD1/PD-L1), either single agent or in&#xD;
        combination with chemotherapy&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1&#xD;
&#xD;
          -  Measurable disease per RECIST version 1.1&#xD;
&#xD;
          -  Diagnoses of advanced/metastatic NSCLC and have failed or are intolerant to 1st line&#xD;
             anti-PD1/PD-L1, either single agent or in combination with chemotherapy, and have&#xD;
             either exhausted or decline or not be candidates for all available standard of care&#xD;
             therapies.&#xD;
&#xD;
          -  Adequate organ function&#xD;
&#xD;
          -  Women of child-bearing potential and men with partners of child-bearing potential must&#xD;
             agree to practice sexual abstinence, or to use an acceptable form of contraception for&#xD;
             the duration of study participation, and for 90 days following completion of therapy&#xD;
&#xD;
          -  Men of child-bearing potential must agree not to donate sperm while on this study and&#xD;
             for 90 days after their last study treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Is not concurrent enrolled in another clinical study, unless it is an observational&#xD;
             (non-interventional) clinical study or if the participant is in the follow-up period&#xD;
             of an interventional study&#xD;
&#xD;
          -  Is not currently on or is not anticipated to use other investigational agents within&#xD;
             14 days prior to and while participating in this study&#xD;
&#xD;
          -  Does not have mixed small cell and non-small cell lung cancer histology&#xD;
&#xD;
          -  Does not have any unresolved toxicity CTCAE &gt;Grade 2 from the prior 1st immunotherapy.&#xD;
             Patients with irreversible toxicity that is not reasonably expected to be exacerbated&#xD;
             by study drug may be included&#xD;
&#xD;
          -  Patients who have targetable mutations that qualify for targeted therapy (e.g.&#xD;
             mutations of epidermal growth factor receptor (EGFR), serine/ threonine- protein&#xD;
             kinase (BRAF), anaplastic lymphoma kinase (ALK), tyrosine- protein kinase (ROS1),&#xD;
             neurotrophic receptor tyrosine kinase (NTRAK)) will be excluded from this study&#xD;
&#xD;
          -  Is not on concomitant therapy intended for the treatment of cancer (including, but not&#xD;
             limited to, chemotherapy, hormonal therapy, immunotherapy, radiotherapy, and herbal&#xD;
             therapy) for 14 days prior to starting study treatment, depending on the agent and&#xD;
             during study treatment, until disease progression is documented and the patient has&#xD;
             discontinued study treatment, with the exception of palliative radiotherapy and local&#xD;
             therapy per PI discretion&#xD;
&#xD;
          -  Does not chronically use a strong cytochrome P4503A4 (CYP3A4/5) inhibitor or inducer,&#xD;
             or sensitive CYP3A substrates with a narrow therapeutic window&#xD;
&#xD;
          -  Has not had recent major surgery within 4 weeks prior to entry into the study&#xD;
             (excluding the placement of vascular access) that would prevent administration of&#xD;
             study drug&#xD;
&#xD;
          -  Does not have uncontrolled systemic disease&#xD;
&#xD;
          -  Does not have uncontrolled brain metastasis&#xD;
&#xD;
          -  Does not have history of allergy to taxanes&#xD;
&#xD;
          -  Does not have history of leptomeningeal carcinomatosis&#xD;
&#xD;
          -  Does not have recent history of myocardial infarction (MI) or symptomatic coronary&#xD;
             artery disease within 6 months of screening&#xD;
&#xD;
          -  Is not receiving active therapy for HIV, hepatitis B or hepatitis C&#xD;
&#xD;
          -  Does not have history of malabsorption syndrome or other condition that would&#xD;
             interfere with enteral absorption or results in the inability or unwillingness to&#xD;
             swallow pills&#xD;
&#xD;
          -  Does not have history of Type I or Type II diabetes mellitus requiring insulin&#xD;
             (Patients who are on a stable dose of oral diabetes medication greater than or equal&#xD;
             to 2 weeks prior to initiation of study treatment&#xD;
&#xD;
          -  Does not have Grade greater than or equal to 2 uncontrolled or untreated&#xD;
             hypercholesterolemia or hypertriglyceridemia&#xD;
&#xD;
          -  Does not have history of or active inflammatory bowel disease (e.g., Crohn's disease&#xD;
             and ulcerative colitis) or active bowel inflammation (e.g., diverticulitis)&#xD;
&#xD;
          -  Does not have active pneumonitis&#xD;
&#xD;
          -  Does not have history of lung disease: interstitial lung disease, idiopathic pulmonary&#xD;
             fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of&#xD;
             opportunistic infections&#xD;
&#xD;
          -  Does not have uncontrolled pleural effusion/pericardial effusion/or ascites as&#xD;
             determined by the investigator&#xD;
&#xD;
          -  Does not have active ventricular arrhythmia requiring medication&#xD;
&#xD;
          -  Does not have psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements or compromise the ability of the patient to give written informed&#xD;
             consent&#xD;
&#xD;
          -  Is not pregnant, breast feeding or planning to become pregnant while receiving study&#xD;
             treatment or for less than 90 days after the last dose of study treatment&#xD;
&#xD;
          -  For males with partners of childbearing potential, is not planning to father a child&#xD;
             or donate sperm while receiving study treatment or for less than 90 days after the&#xD;
             last dose of study treatment&#xD;
&#xD;
          -  Does not have any condition that, in the opinion of the investigator, would interfere&#xD;
             with evaluation or interpretation of patient safety or study results&#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>Jun Zhang, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of Kansas</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>KUCC Navigator</last_name>
    <phone>9135883671</phone>
    <email>KUCC_Navigation@kumc.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>The University of Kansas Cancer Center (KUCC)</name>
      <address>
        <city>Fairway</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Clinical Trials Nurse Navigator</last_name>
      <phone>913-945-7552</phone>
      <email>ctnursenav@kumc.edu</email>
    </contact>
    <contact_backup>
      <last_name>Steve Williamson, MD</last_name>
      <phone>913-588-3808</phone>
      <email>SWILLIAM@kumc.edu</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>The University of Kansas Cancer Center, Westwood Campus</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Clinical Trials Nurse Navigator</last_name>
      <phone>913-945-7552</phone>
      <email>ctnursenav@kumc.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>The University of Kansas Cancer Center, Overland Park Clinic</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66210</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>The University of Kansas Cancer Center, North Clinic</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64154</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>The University of Kansas Cancer Center, Lee's Summit Clinic</name>
      <address>
        <city>Lee's Summit</city>
        <state>Missouri</state>
        <zip>64064</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>June 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <last_update_submitted>February 5, 2023</last_update_submitted>
  <last_update_submitted_qc>February 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Kansas Medical Center</investigator_affiliation>
    <investigator_full_name>Jun Zhang, MD, PhD</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Advanced/metastatic NSCLC</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ipatasertib</mesh_term>
  </intervention_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/NCT04467801
org study id: IIT-2019-IpatTax
nct id: NCT04467801
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
For metastatic/advanced NSCLC patients who do not have targetable mutations, either
      immunotherapy targeting the programmed death-1 and its ligand (PD-1/L1) pathway alone or in
      combination with platinum doublet chemotherapy is now a standard of care. However, still
      about half of the patients do not benefit due to treatment resistance. It is therefore
      critically important to find novel therapies and combinations to benefit patients who have
      failed or are intolerant to 1st line immunotherapy.

      This study hypothesizes that ipatasertib in combination with taxane (e.g. docetaxel) can be
      an effective strategy. Ipatasertib is a novel adenosine triphosphate (ATP)-competitive
      inhibitor that has demonstrated robust and selective targeting of protein kinase B (PKB, also
      known as AKT) in cancer patients. Importantly, evidence from preclinical studies has
      demonstrated that AKT inhibitors (e.g. ipatasertib) can enhance the therapeutic effect of
      chemotherapy as well as immunotherapy via modulating Phosphatidylinositol 3-kinase
      (PI3'K)-AKT activity.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression Free Survival
time frame: up to 12 months
description: RECIST 1.1
measure: Number of adverse events experienced by participants receiving treatment with ipatasertib in combination with docetaxel
time frame: At cycle 1day 8 (each cycle is 21 days) up to 2 months (60 days) after End of treatment
description: CTCAE Version 5.0
measure: Overall Response Rate
time frame: every 6 weeks up to 12 months
description: RECIST 1.1
measure: Overall Survival
time frame: Cycle 1day 1 (each cycle is 21 days) to up to 12 months after end of treatment
description: Medical record
arm group label: Treatment
arm group type: Experimental
description: Ipatasertib, 400 mg once daily, Oral, Days 1-14 of each 21 day cycle (2 weeks on and 1 week off).
Docetaxel, 75 mg/m2, Intra-venous, Day 1 of each 21 day cycle.
intervention type: Drug
intervention name: Ipatasertib
description: Ipatasertib is a novel ATP-competitive inhibitor. It is taken by mouth once daily.
arm group label: Treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jun Zhang, MD, PhD
role: Principal Investigator
affiliation: The University of Kansas
last name: KUCC Navigator
phone: 9135883671
email: KUCC_Navigation@kumc.edu
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Kansas Medical Center
investigator full name: Jun Zhang, MD, PhD
investigator title: MD, PhD
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Ipatasertib
sharing ipd: No