<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/NCT03011671</url>
  </required_header>
  <id_info>
    <org_study_id>IRB16-0767</org_study_id>
    <nct_id>NCT03011671</nct_id>
  </id_info>
  <brief_title>Study of Acetazolamide With Temozolomide in Adults With Newly Diagnosed or Recurrent Malignant Glioma</brief_title>
  <official_title>A Phase I Study of Safety and Tolerability of Acetazolamide With Temozolomide in Adults With Newly Diagnosed MGMT Promoter-Methylated IDH Wildtype Glioblastoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Chicago</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Chicago</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>
      This is a Phase I study that examines the rate of dose limiting side effects in patients with&#xD;
      malignant astrocytoma treated with combination acetazolamide (ACZ) and temozolomide (TMZ).&#xD;
      Eligible patients must have histologically proven newly diagnosed, O6-methylguanine-DNA&#xD;
      methyltransferase (MGMT) methylated WHO grade III or IV astrocytoma and be planning to&#xD;
      undergo treatment with standard adjuvant TMZ (after completing treatment with TMZ and&#xD;
      ionizing radiation (IR)).&#xD;
&#xD;
      During this study, patients will receive daily oral ACZ with TMZ. During each cycle, ACZ will&#xD;
      be started on the day of TMZ initiation and continued for a total of 21 days.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 3, 2018</start_date>
  <completion_date type="Anticipated">October 2026</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2026</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>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with adverse events</measure>
    <time_frame>28 Days</time_frame>
    <description>To determine the safety, tolerability and adverse event profile of adding acetazolamide to temozolomide in patients with newly diagnosed malignant astrocytoma.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measure objective response rate (ORR); change in tumor size</measure>
    <time_frame>6 months</time_frame>
    <description>ORR will be determined at 6 months and is based on the change in tumor size (as determined by Response Assessment in Neuro-Oncology Criteria (RANO) criteria) at the indicated time relative to the pre-treatment scan. RANO criteria will also be used to define disease status (CR, PR, etc.).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time until progression free survival (PFS)</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time until overall survival (OS)</measure>
    <time_frame>From start date of therapy to the date of death from any cause, whichever may come first, assessed up to 100 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Analysis of formalin fixed paraffin embedded surgical specimens.</measure>
    <time_frame>Through study completion an average of one year</time_frame>
    <description>Bcl-3 expression will be determined by an independent neuro-pathologist by immunohistochemical analysis of formalin fixed paraffin embedded (FFPE) surgical specimens. This is to evaluate Bcl-3 expression level within each tumor and preliminarily examine the ability of Bcl-3 to predict response to TMZ and the efficacy of adding ACZ.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine feasibility of cooperative interaction between multiple sites</measure>
    <time_frame>End of study enrollment period (approximately 6 years)</time_frame>
    <description>Feasibility to be determined based on ability to complete accrual to the study</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Malignant Glioma of Brain</condition>
  <arm_group>
    <arm_group_label>Acetazolamide with Temozolomide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive daily ACZ together with TMZ in 28 day cycles for up to 6 cycles if they do not experience either disease worsening or unacceptable side effects.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acetazolamide</intervention_name>
    <description>ACZ will be given at an initial dose of 250 mg twice a day (BID) and then escalated to 500 mg BID after 1 week. ACZ will be given on days 1-21 of each cycle.</description>
    <arm_group_label>Acetazolamide with Temozolomide</arm_group_label>
    <other_name>Diamox</other_name>
    <other_name>Diamox Sequels</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Temozolomide</intervention_name>
    <description>For cycle 1 of the maintenance phase, TMZ will administered at 150 mg/m2 on days 1- 5 followed by 23 days with no drug. For cycles 2- 6, TMZ can be increased to 200 mg/m2 at the discretion of the treating investigator.</description>
    <arm_group_label>Acetazolamide with Temozolomide</arm_group_label>
    <other_name>Temodar</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically proven, newly diagnosed IDH wildtype glioblastoma (GBM) that has a&#xD;
             methylated MGMT promoter as assessed by the standardized institutional analysis.&#xD;
&#xD;
          -  Patients are eligible if they had a prior low grade astrocytoma and there is&#xD;
             subsequent histological evidence of a diagnosis of grade III or IV tumor.&#xD;
&#xD;
          -  Patients must be receiving TMZ as part of their standard adjuvant treatment regimen&#xD;
             following treatment with TMZ and Radiation.&#xD;
&#xD;
          -  Patients must have a Karnofsky performance ≥ 60%.&#xD;
&#xD;
          -  Normal organ function as follows:&#xD;
&#xD;
               -  Absolute Neutrophil Count (ANC) ≥ 1.0 x 10^9/ L&#xD;
&#xD;
               -  Platelets ≥ 100 x 10^9 / L&#xD;
&#xD;
               -  Hemoglobin ≥ 8.0 g / dL&#xD;
&#xD;
          -  Age 18 years or older.&#xD;
&#xD;
          -  Kidney function (creatinine level within normal institutional limit, or creatinine&#xD;
             clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine level above institutional&#xD;
             normal).&#xD;
&#xD;
          -  Liver function (AST/ALT &lt;2.5 X institutional upper limit of normal (ULN), Total&#xD;
             bilirubin ≤ 1.5 times ULN, INR within 1.5 times ULN (or if receiving anticoagulant&#xD;
             therapy an INR of ≤ 3.0 is allowed with concomitant increase in PT or an aPTT ≤ 2.5 ×&#xD;
             control).&#xD;
&#xD;
          -  Women able to become pregnant must have a negative pregnancy test within 30 days of&#xD;
             registration.&#xD;
&#xD;
          -  Patients must have the ability to understand and the willingness to sign a written&#xD;
             informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior invasive malignancy that is not low-grade glioma (except non-melanomatous skin&#xD;
             cancer or carcinoma in situ of the cervix) unless the patient has been disease free&#xD;
             and off therapy for that disease for a minimum of 3 years.&#xD;
&#xD;
          -  Active systemic infection requiring treatment, including any HIV infection or&#xD;
             toxoplasmosis.&#xD;
&#xD;
          -  Other severe acute or chronic medical or psychiatric condition, or laboratory&#xD;
             abnormality that may increase the risk associated with study participation or study&#xD;
             drug administration.&#xD;
&#xD;
          -  Systemic corticosteroid therapy, &gt;8 mg of dexamethasone daily (or equivalent) at study&#xD;
             enrollment.&#xD;
&#xD;
          -  Pregnant women are excluded from this study, where pregnancy is confirmed by a&#xD;
             positive serum beta-hCG laboratory test. Breast-feeding should be discontinued.&#xD;
&#xD;
          -  Hypersensitivity to acetazolamide or sulfonamides.&#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>Bakhtiar Yamini, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Chicago</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Bakhtiar Yamini, M.D.</last_name>
    <phone>773-702-2123</phone>
    <email>byamini@surgery.bsd.uchicago.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Chicago Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bakhtiar Yamini, MD</last_name>
      <email>byamini@surgery.bsd.uchicago.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>January 4, 2017</study_first_submitted>
  <study_first_submitted_qc>January 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 5, 2017</study_first_posted>
  <last_update_submitted>March 2, 2023</last_update_submitted>
  <last_update_submitted_qc>March 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Malignant Glioma of Brain</keyword>
  <keyword>Acetazolamide</keyword>
  <keyword>Temozolomide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Temozolomide</mesh_term>
    <mesh_term>Acetazolamide</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/NCT03011671
org study id: IRB16-0767
nct id: NCT03011671
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase I study that examines the rate of dose limiting side effects in patients with
      malignant astrocytoma treated with combination acetazolamide (ACZ) and temozolomide (TMZ).
      Eligible patients must have histologically proven newly diagnosed, O6-methylguanine-DNA
      methyltransferase (MGMT) methylated WHO grade III or IV astrocytoma and be planning to
      undergo treatment with standard adjuvant TMZ (after completing treatment with TMZ and
      ionizing radiation (IR)).

      During this study, patients will receive daily oral ACZ with TMZ. During each cycle, ACZ will
      be started on the day of TMZ initiation and continued for a total of 21 days.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with adverse events
time frame: 28 Days
description: To determine the safety, tolerability and adverse event profile of adding acetazolamide to temozolomide in patients with newly diagnosed malignant astrocytoma.
measure: Measure objective response rate (ORR); change in tumor size
time frame: 6 months
description: ORR will be determined at 6 months and is based on the change in tumor size (as determined by Response Assessment in Neuro-Oncology Criteria (RANO) criteria) at the indicated time relative to the pre-treatment scan. RANO criteria will also be used to define disease status (CR, PR, etc.).
measure: Time until progression free survival (PFS)
time frame: 6 months
measure: Time until overall survival (OS)
time frame: From start date of therapy to the date of death from any cause, whichever may come first, assessed up to 100 months
measure: Analysis of formalin fixed paraffin embedded surgical specimens.
time frame: Through study completion an average of one year
description: Bcl-3 expression will be determined by an independent neuro-pathologist by immunohistochemical analysis of formalin fixed paraffin embedded (FFPE) surgical specimens. This is to evaluate Bcl-3 expression level within each tumor and preliminarily examine the ability of Bcl-3 to predict response to TMZ and the efficacy of adding ACZ.
measure: To determine feasibility of cooperative interaction between multiple sites
time frame: End of study enrollment period (approximately 6 years)
description: Feasibility to be determined based on ability to complete accrual to the study
arm group label: Acetazolamide with Temozolomide
arm group type: Experimental
description: Subjects will receive daily ACZ together with TMZ in 28 day cycles for up to 6 cycles if they do not experience either disease worsening or unacceptable side effects.
intervention type: Drug
intervention name: Acetazolamide
description: ACZ will be given at an initial dose of 250 mg twice a day (BID) and then escalated to 500 mg BID after 1 week. ACZ will be given on days 1-21 of each cycle.
arm group label: Acetazolamide with Temozolomide
other name: Diamox
other name: Diamox Sequels
intervention type: Drug
intervention name: Temozolomide
description: For cycle 1 of the maintenance phase, TMZ will administered at 150 mg/m2 on days 1- 5 followed by 23 days with no drug. For cycles 2- 6, TMZ can be increased to 200 mg/m2 at the discretion of the treating investigator.
arm group label: Acetazolamide with Temozolomide
other name: Temodar
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bakhtiar Yamini, MD
role: Principal Investigator
affiliation: University of Chicago
last name: Bakhtiar Yamini, M.D.
phone: 773-702-2123
email: byamini@surgery.bsd.uchicago.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor
mesh term: Glioma
mesh term: Temozolomide
mesh term: Acetazolamide