<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/NCT02207010</url>
  </required_header>
  <id_info>
    <org_study_id>BBTRC 001</org_study_id>
    <nct_id>NCT02207010</nct_id>
  </id_info>
  <brief_title>A Phase 0 Study of AZD1775 in Recurrent GBM Patients</brief_title>
  <official_title>A Phase 0 Study of AZD1775 in Preoperative Glioblastoma Multiforme (GBM) Patients Scheduled for Resection to Evaluate for Central Nervous System (CNS) Penetration</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Joseph's Hospital and Medical Center, Phoenix</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Ben &amp; Catherine Ivy Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>American Society of Clinical Oncology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Barbara Ann Karmanos Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Translational Genomics Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>St. Joseph's Hospital and Medical Center, Phoenix</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study would test how much of the new drug, AZD1775, is present in tumor, blood, and skin&#xD;
      after one dose of the drug.&#xD;
&#xD;
      The purpose of the study is not to treat the tumor, but to see if the drug actually gets into&#xD;
      the tumor cells. This study does not replace routine cancer treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients will be administered one dose of AZD1775 prior to surgical resection of their tumor.&#xD;
      There will be 2 portions of this trial, referred to as Part 1 and Part 2. Part 1 will involve&#xD;
      a dose escalation strategy where 3 separate doses (100, 200, and 400mg) will be evaluated.&#xD;
      Each dose cohort will involve 4 patients. Surgery, with tissue harvest for determination of&#xD;
      both tissue drug level and biomarker evaluation, will occur at 8 hrs post drug&#xD;
      administration.&#xD;
&#xD;
      Part 2 will determine the potential tumor drug level and PD effects at various time intervals&#xD;
      after drug administration of a single select drug dose. Currently, we are planning to use a&#xD;
      dose (200 mg) that has been deemed safe when used in combination with cytotoxic therapy.&#xD;
      However, if results from Part 1 suggest an alternate dose may be preferable, we will consider&#xD;
      using that alternate dose in Part 2. Dosing will be followed by surgical resection at 2-4 hrs&#xD;
      and at 22-26 hrs post dose.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2014</start_date>
  <completion_date type="Actual">March 25, 2019</completion_date>
  <primary_completion_date type="Actual">December 31, 2015</primary_completion_date>
  <phase>Early 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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Plasma concentration of AZD1775 following single dose of AZD1775</measure>
    <time_frame>at baseline, 2-4, 8-12, and 22-26 hours following single dose of AZD1775</time_frame>
    <description>Will be summarized using descriptive statistics</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Intratumoral concentration of AZD1775</measure>
    <time_frame>up to day of surgery</time_frame>
    <description>Will be summarized using descriptive statistics</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Degree of CDC2 (Tyr15) phosphorylation in tissue</measure>
    <time_frame>at baseline and up to 26 hours post dosing</time_frame>
    <description>Will be summarized using descriptive statistics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of GBM cells in M-phase of cell cycle (PH3)</measure>
    <time_frame>at baseline and up to 26 hours post dose AZD1775</time_frame>
    <description>Will be summarized using descriptive statistics</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of double-strand DNA damage (γH2AX).</measure>
    <time_frame>at baseline and up to 26 hours post dose AZD1775</time_frame>
    <description>Will be summarized using descriptive statistics</description>
  </secondary_outcome>
  <other_outcome>
    <measure>P53 mutation status</measure>
    <time_frame>up to time of surgery</time_frame>
    <description>Will be summarized using descriptive statistics</description>
  </other_outcome>
  <other_outcome>
    <measure>Presence of checkpoint regulator genes in GBM specimens</measure>
    <time_frame>up to time of surgery</time_frame>
    <description>checkpoint regulator genes in GBM specimens</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Glioblastoma</condition>
  <condition>GBM</condition>
  <arm_group>
    <arm_group_label>AZD1775</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive a single dose (either 100 mg, 200 mg or 400 mg) of AZD1775, an oral agent, prior to surgery for resection of GBM</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>AZD1775</intervention_name>
    <description>All patients receive a single dose of the oral study drug prior to surgery for resection of GBM.</description>
    <arm_group_label>AZD1775</arm_group_label>
    <other_name>Wee1 inhibitor</other_name>
    <other_name>MK1775</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with 1 prior resection of histologically-diagnosed de novo GBM&#xD;
&#xD;
          2. Patient must have MRI evidence of disease recurrence&#xD;
&#xD;
          3. Patients must have Eastern Cooperative Oncology Group (ECOG) performance status ≤2&#xD;
&#xD;
          4. Patients ≥ 18 years of age&#xD;
&#xD;
          5. Adequate hematologic, renal, and hepatic function&#xD;
&#xD;
          6. Patients must not have co-morbid condition(s) that, at the opinion of the&#xD;
             investigator, prevent safe surgical treatment&#xD;
&#xD;
          7. Patients must not have active infection or fever &gt; 38.5°C&#xD;
&#xD;
          8. Patients must not be pregnant or nursing&#xD;
&#xD;
          9. Patients must have archival tumor tissue block available for research use&#xD;
&#xD;
         10. Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
         11. Patient has voluntarily agreed to participate by giving written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Less than 18 years of age&#xD;
&#xD;
          2. Diagnosis of anything other than first-recurrence GBM&#xD;
&#xD;
          3. GBM tissue from first-resection not available&#xD;
&#xD;
          4. Previous treatment with AZD1775&#xD;
&#xD;
          5. Uncontrolled concurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements&#xD;
&#xD;
          6. Patient has known hypersensitivity to the components of potential study therapy or its&#xD;
             analogs.&#xD;
&#xD;
          7. Patient has had prescription or non-prescription drugs or other products known to be&#xD;
             metabolized by cytochrome P450 3A4 (CYP3A4), or to inhibit or induce CYP3A4, which&#xD;
             cannot be discontinued prior to Day 1 of dosing and withheld throughout the study&#xD;
             until 2 weeks after the last dose of study medication (inhibitors generally for 5&#xD;
             half-lives). Medications of particular concern are the following inhibitors of CYP3A4:&#xD;
             azole antifungals (ketoconazole itraconazole, fluconazole and voriconazole), macrolide&#xD;
             antibiotics (erythromycin, clarithromycin), cimetidine, HIV protease inhibitors,&#xD;
             nefazodone and the following inducers of CYP3A4: phenytoin, barbiturates and&#xD;
             rifampicin. Substrates of CYP3A4 include statins (lovastatin, simvastatin), midazolam,&#xD;
             terfenadine, astemizole, and cisapride. CYP3A4.&#xD;
&#xD;
          8. Patient has a history or current evidence of any condition, therapy, or lab&#xD;
             abnormality that might confound the results of the study, interfere with the patient's&#xD;
             participation for the full duration of the study, or is not in the best interest of&#xD;
             the patient to participate.&#xD;
&#xD;
          9. Patient has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial.&#xD;
&#xD;
         10. Patient is, at the time of signing informed consent, a regular user (including&#xD;
             &quot;recreational use&quot;) of any illicit drugs or had a recent history (within the last&#xD;
             year) of drug or alcohol abuse.&#xD;
&#xD;
         11. Patients expecting to reproduce within the projected duration of the study (estimated&#xD;
             to be 1 year), and women who are pregnant or breastfeeding.&#xD;
&#xD;
         12. Patient is known to be suffering from Acquired Immune Deficiency Syndrome (AIDS).&#xD;
&#xD;
         13. Patient has known history of Hepatitis B or C.&#xD;
&#xD;
         14. Patient has symptomatic ascites or pleural effusion. A patient who is clinically&#xD;
             stable following treatment for these conditions is eligible.&#xD;
&#xD;
         15. Patient has a clinical history suggestive of Li-Fraumeni Syndrome.&#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>Nader Sanai, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Barrow Neurological Institute at St.Joseph's Hospital Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Barrow Neurological Institute at St. Joseph's Hospital Medical Center</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85013</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>July 28, 2014</study_first_submitted>
  <study_first_submitted_qc>July 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 1, 2014</study_first_posted>
  <last_update_submitted>December 9, 2020</last_update_submitted>
  <last_update_submitted_qc>December 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 10, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Glioblastoma</keyword>
  <keyword>GBM</keyword>
  <keyword>first recurrence</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioblastoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adavosertib</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/NCT02207010
org study id: BBTRC 001
nct id: NCT02207010
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
This study would test how much of the new drug, AZD1775, is present in tumor, blood, and skin
      after one dose of the drug.

      The purpose of the study is not to treat the tumor, but to see if the drug actually gets into
      the tumor cells. This study does not replace routine cancer treatment.
Patients will be administered one dose of AZD1775 prior to surgical resection of their tumor.
      There will be 2 portions of this trial, referred to as Part 1 and Part 2. Part 1 will involve
      a dose escalation strategy where 3 separate doses (100, 200, and 400mg) will be evaluated.
      Each dose cohort will involve 4 patients. Surgery, with tissue harvest for determination of
      both tissue drug level and biomarker evaluation, will occur at 8 hrs post drug
      administration.

      Part 2 will determine the potential tumor drug level and PD effects at various time intervals
      after drug administration of a single select drug dose. Currently, we are planning to use a
      dose (200 mg) that has been deemed safe when used in combination with cytotoxic therapy.
      However, if results from Part 1 suggest an alternate dose may be preferable, we will consider
      using that alternate dose in Part 2. Dosing will be followed by surgical resection at 2-4 hrs
      and at 22-26 hrs post dose.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Plasma concentration of AZD1775 following single dose of AZD1775
time frame: at baseline, 2-4, 8-12, and 22-26 hours following single dose of AZD1775
description: Will be summarized using descriptive statistics
measure: Intratumoral concentration of AZD1775
time frame: up to day of surgery
description: Will be summarized using descriptive statistics
measure: Degree of CDC2 (Tyr15) phosphorylation in tissue
time frame: at baseline and up to 26 hours post dosing
description: Will be summarized using descriptive statistics
measure: Number of GBM cells in M-phase of cell cycle (PH3)
time frame: at baseline and up to 26 hours post dose AZD1775
description: Will be summarized using descriptive statistics
measure: Presence of double-strand DNA damage (γH2AX).
time frame: at baseline and up to 26 hours post dose AZD1775
description: Will be summarized using descriptive statistics
measure: P53 mutation status
time frame: up to time of surgery
description: Will be summarized using descriptive statistics
measure: Presence of checkpoint regulator genes in GBM specimens
time frame: up to time of surgery
description: checkpoint regulator genes in GBM specimens
arm group label: AZD1775
arm group type: Experimental
description: Patients will receive a single dose (either 100 mg, 200 mg or 400 mg) of AZD1775, an oral agent, prior to surgery for resection of GBM
intervention type: Biological
intervention name: AZD1775
description: All patients receive a single dose of the oral study drug prior to surgery for resection of GBM.
arm group label: AZD1775
other name: Wee1 inhibitor
other name: MK1775
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nader Sanai, MD
role: Principal Investigator
affiliation: Barrow Neurological Institute at St.Joseph's Hospital Medical Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Glioblastoma
mesh term: Adavosertib