<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/NCT03243331</url>
  </required_header>
  <id_info>
    <org_study_id>IUSCC-0613</org_study_id>
    <nct_id>NCT03243331</nct_id>
  </id_info>
  <brief_title>An Initial Safety Study of Gedatolisib Plus PTK7-ADC for Metastatic Triple-negative Breast Cancer</brief_title>
  <official_title>An Initial Safety Study of Gedatolisib Plus PTK7-ADC for Metastatic Triple-negative Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kathy Miller</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Indiana University</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>
      Phase 1 study to evaluate the safety and effect of Gedatolisib and PTK7-ADC for the treatment&#xD;
      of triple negative breast cancer&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 19, 2018</start_date>
  <completion_date type="Actual">May 27, 2020</completion_date>
  <primary_completion_date type="Actual">May 27, 2020</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>Sequential Assignment</intervention_model>
    <intervention_model_description>Study will enroll 3 patients to the cohort 1 dose level. If 0 of 3 patients experience a DLT, the study will proceed to cohort 2. If 1 patient experiences a DLT, 3 additional patients will be enrolled into cohort 1. If 1 of 6 patients experience a DLT, the study will proceed and 3 patients will be enrolled to the cohort 2 dose level. If 0 patients experience a DLT in cohort 2, the study will proceed to cohort 3. If 1 patient experiences a DLT at cohort 2, 3 additional patients will be enrolled into cohort 2. If the study proceeds to cohort 3, 3 patients will be enrolled at this dose level. If 0 patients experience a DLT, the study will enroll an additional 3 patients at the cohort 3 dose level to better define the safety profile. If 1 of 3 patients experiences a DLT at cohort 3, 3 additional patients will still be enrolled into cohort 3. If 1 of 6 patients experience a DLT, the study will complete.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety of Gedatolisb + PTK7-ADC using NCI CTCAE v4.0</measure>
    <time_frame>through study completion i.e. up to 1 year</time_frame>
    <description>safety and toxicity data will be assessed using NCI CTCAE v4.0 and tabulated and reported</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy in all enrolled subjects</measure>
    <time_frame>18 weeks</time_frame>
    <description>efficacy as determined by clinical benefit at 18 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate in all enrolled subjects</measure>
    <time_frame>through study completion i.e. up to 1 year</time_frame>
    <description>efficacy as determined by overall response rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival in all enrolled subjects</measure>
    <time_frame>through study completion i.e. up to 1 year</time_frame>
    <description>efficacy as determined by progression free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic determination of inhibition of PI3k signaling</measure>
    <time_frame>Cycle 1 Day 15</time_frame>
    <description>Pathological H-score will be determined from tissue obtained at screening and Cycle 1 Day 15. H-score will be compared to calculate percentage inhibition between samples.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic determination modulation of Wnt pathway</measure>
    <time_frame>Cycle 1 Day 15</time_frame>
    <description>pathological H-score will be determined from tissue obtained at screening and Cycle 1 Day 15. H-score will be compared to calculate percentage change in expression between samples.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic determination modulation of Wnt pathway</measure>
    <time_frame>Cycle 1 Day 15</time_frame>
    <description>RNA sequencing of tissue collected at screening and Cycle 1 Day 1 to compare Wnt pathway expression after treatment</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Triple Negative Breast Cancer</condition>
  <condition>Metastatic Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Gedatolisb + PTK7-ADC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gedatolisib</intervention_name>
    <description>Gedatolisb will be intravenously administered on Day 1, Day 8 and Day 15 of every 21 day cycle at a dose of 110 mg or 180mg depending on cohort assignment.</description>
    <arm_group_label>Gedatolisb + PTK7-ADC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PTK7-ADC</intervention_name>
    <description>PTK7-ADC will be administered on Day 1 of every 21 day cycle at a dose of 1.4mg/kg or 2.8 mg/kg depending on cohort assignment.</description>
    <arm_group_label>Gedatolisb + PTK7-ADC</arm_group_label>
    <other_name>PF-06647020</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Metastatic Triple-negative Breast Cancer&#xD;
&#xD;
          -  Willingness to undergo tumor biopsy&#xD;
&#xD;
          -  Patients must have received at least 1 prior chemotherapy regimen for metastatic&#xD;
             disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous treatment with mTOR inhibitor&#xD;
&#xD;
          -  Untreated brain metastases&#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>Kathy Miller, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Indiana University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Milan Radovich, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Indiana University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>IU Simon Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>August 3, 2017</study_first_submitted>
  <study_first_submitted_qc>August 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 9, 2017</study_first_posted>
  <last_update_submitted>January 5, 2021</last_update_submitted>
  <last_update_submitted_qc>January 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 7, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Indiana University</investigator_affiliation>
    <investigator_full_name>Kathy Miller</investigator_full_name>
    <investigator_title>Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Breast Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gedatolisib</mesh_term>
  </intervention_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/NCT03243331
org study id: IUSCC-0613
nct id: NCT03243331
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Phase 1 study to evaluate the safety and effect of Gedatolisib and PTK7-ADC for the treatment
      of triple negative breast cancer
allocation: N/A
intervention model: Sequential Assignment
intervention model description: Study will enroll 3 patients to the cohort 1 dose level. If 0 of 3 patients experience a DLT, the study will proceed to cohort 2. If 1 patient experiences a DLT, 3 additional patients will be enrolled into cohort 1. If 1 of 6 patients experience a DLT, the study will proceed and 3 patients will be enrolled to the cohort 2 dose level. If 0 patients experience a DLT in cohort 2, the study will proceed to cohort 3. If 1 patient experiences a DLT at cohort 2, 3 additional patients will be enrolled into cohort 2. If the study proceeds to cohort 3, 3 patients will be enrolled at this dose level. If 0 patients experience a DLT, the study will enroll an additional 3 patients at the cohort 3 dose level to better define the safety profile. If 1 of 3 patients experiences a DLT at cohort 3, 3 additional patients will still be enrolled into cohort 3. If 1 of 6 patients experience a DLT, the study will complete.
primary purpose: Treatment
masking: None (Open Label)
measure: Safety of Gedatolisb + PTK7-ADC using NCI CTCAE v4.0
time frame: through study completion i.e. up to 1 year
description: safety and toxicity data will be assessed using NCI CTCAE v4.0 and tabulated and reported
measure: Efficacy in all enrolled subjects
time frame: 18 weeks
description: efficacy as determined by clinical benefit at 18 weeks
measure: Overall response rate in all enrolled subjects
time frame: through study completion i.e. up to 1 year
description: efficacy as determined by overall response rate
measure: Progression free survival in all enrolled subjects
time frame: through study completion i.e. up to 1 year
description: efficacy as determined by progression free survival
measure: Pharmacodynamic determination of inhibition of PI3k signaling
time frame: Cycle 1 Day 15
description: Pathological H-score will be determined from tissue obtained at screening and Cycle 1 Day 15. H-score will be compared to calculate percentage inhibition between samples.
measure: Pharmacodynamic determination modulation of Wnt pathway
time frame: Cycle 1 Day 15
description: pathological H-score will be determined from tissue obtained at screening and Cycle 1 Day 15. H-score will be compared to calculate percentage change in expression between samples.
measure: Pharmacodynamic determination modulation of Wnt pathway
time frame: Cycle 1 Day 15
description: RNA sequencing of tissue collected at screening and Cycle 1 Day 1 to compare Wnt pathway expression after treatment
arm group label: Gedatolisb + PTK7-ADC
arm group type: Experimental
intervention type: Drug
intervention name: Gedatolisib
description: Gedatolisb will be intravenously administered on Day 1, Day 8 and Day 15 of every 21 day cycle at a dose of 110 mg or 180mg depending on cohort assignment.
arm group label: Gedatolisb + PTK7-ADC
intervention type: Drug
intervention name: PTK7-ADC
description: PTK7-ADC will be administered on Day 1 of every 21 day cycle at a dose of 1.4mg/kg or 2.8 mg/kg depending on cohort assignment.
arm group label: Gedatolisb + PTK7-ADC
other name: PF-06647020
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kathy Miller, MD
role: Principal Investigator
affiliation: Indiana University
last name: Milan Radovich, PhD
role: Principal Investigator
affiliation: Indiana University
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Indiana University
investigator full name: Kathy Miller
investigator title: Professor of Medicine
mesh term: Breast Neoplasms
mesh term: Triple Negative Breast Neoplasms
mesh term: Gedatolisib