xml: <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/NCT06011109</url>
    </required_header>
    <id_info>
      <org_study_id>AVTA 22-01</org_study_id>
      <nct_id>NCT06011109</nct_id>
    </id_info>
    <brief_title>Treatment of Patients With Recurrent High-Grade Glioma With APG-157 and Bevacizumab</brief_title>
    <official_title>A Pilot Study of APG-157 With Bevacizumab for Patients With Recurrent High-Grade Glioma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Aveta Biomics, Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Aveta Biomics, Inc.</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>
        The goal of this interventional study is to evaluate the efficacy of APG-157 in combination&#xD;
        with Bevacizumab in subjects with recurrent high-grade glioma. The main questions the study&#xD;
        aims to answer are:&#xD;
  &#xD;
          -  Progression-free and overall survival of patients receiving this combination;&#xD;
  &#xD;
          -  Quality of Life (QOL); and&#xD;
  &#xD;
          -  Tumor response on imaging&#xD;
  &#xD;
        The participants will take APG-157 daily by dissolving two pastilles in their mouth at around&#xD;
        breakfast, lunch and dinner time (total of six pastilles per day). The pastilles dissolve in&#xD;
        the mouth.&#xD;
  &#xD;
        The participants will continue to receive Bevacizumab as standard of care.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The goal of this interventional study is to evaluate the efficacy of APG-157 in combination&#xD;
        with Bevacizumab in subjects with recurrent high-grade glioma who have previously progressed&#xD;
        on bevacizumab alone. The main questions the study aims to answer are:&#xD;
  &#xD;
          -  Progression-free and overall survival of patients receiving this combination;&#xD;
  &#xD;
          -  Quality of Life (QOL); and&#xD;
  &#xD;
          -  Tumor response on imaging&#xD;
  &#xD;
        Additional aims include:&#xD;
  &#xD;
          -  characterization of pharmacokinetics (PK) of APG-157 in the presence of bevacizumab; and&#xD;
  &#xD;
          -  optionally serum changes in VEGF and HIF-1 alpha, if the study shows preliminary&#xD;
             indication of efficacy&#xD;
  &#xD;
        The participants will take APG-157 daily by dissolving two pastilles in their mouth at around&#xD;
        breakfast, lunch and dinner time (total of 6 pastilles per day). The pastilles dissolve in&#xD;
        the mouth.&#xD;
  &#xD;
        The participants will continue to receive Bevacizumab and be present for scheduled visits and&#xD;
        examinations as standard of care.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 15, 2023</start_date>
    <completion_date type="Anticipated">January 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
    <phase>Phase 1/Phase 2</phase>
    <study_type>Interventional</study_type>
    <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>From date of commencement of treatment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months</time_frame>
      <description>To evaluate progression-free survival of participants with recurrent high-grade glioma treated with APG-157 and Bevacizumab. Progression of the disease will be assessed using commonly used imaging modality such as Magnetic Resonance Imaging or CT scan.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Overall Survival</measure>
      <time_frame>From date of commencement of treatment until the date of death from any cause. Duration of assessment will be 12 months from the date of commencement of the treatment.</time_frame>
      <description>To evaluate overall survival of participants with recurrent high-grade glioma treated with APG-157 and Bevacizumab</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>QOL assessment (EORTC QLQ-C30)</measure>
      <time_frame>Every 8 weeks; from date of commencement of treatment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months</time_frame>
      <description>Descriptively examine quality of life (QOL) using EORTC QLQ-C30 (Organization for Research and Treatment in Cancer Quality of Life Questionnaire C30). EORTC QLQ-C30 is a standardized questionnaire that rates function, symptoms and health status from patient perspective using various questions on a scale of 1 - 4 where generally 1 is rated as normal or no issue (not at all) and 4 being the maximum adverse impact being experienced (very much).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Radiographic studies MRI or CT of the brain</measure>
      <time_frame>Every 8 weeks; from date of commencement of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months</time_frame>
      <description>To measure tumor size in response to treatment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics (PK) of APG-157</measure>
      <time_frame>At three timepoints: at start of dosing; at end of cycle 1 (each cycle is 28 days); and at end of cycle 2 after start of dosing.</time_frame>
      <description>Measure the amount of APG-157 components in the blood in the presence of bevacizumab</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Glioma</condition>
    <condition>Glioblastoma Multiforme</condition>
    <arm_group>
      <arm_group_label>APG-157</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The participants will receive APG-157 daily by taking two pastilles in their mouth at around breakfast, lunch and dinner time (total of six pastilles per day). The pastilles dissolve in the mouth.&#xD;
  The participants will continue to receive Bevacizumab as standard of care.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>APG-157</intervention_name>
      <description>The participants will receive APG-157 daily; and continue to receive Bevacizumab as standard of care.</description>
      <arm_group_label>APG-157</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Patients must have pathologically proven diagnosis of high grade (aka grade III or IV)&#xD;
               glioma that has progressed on bevacizumab (anaplastic astrocytoma, anaplastic&#xD;
               oligodendroglioma, glioblastoma, gliosarcoma, H3K27M mutant glioma).&#xD;
  &#xD;
            2. Patients must have received prior radiation therapy and standard temozolomide.&#xD;
               Patients who have received any number of therapies for previous progressions will be&#xD;
               considered eligible.&#xD;
  &#xD;
            3. Patients must be three or more months from the end of chemoradiotherapy or have biopsy&#xD;
               or imaging consistent with disease progression.&#xD;
  &#xD;
            4. Physiologic Status/Age: Patients must be 19 years of age or older (the age of consent&#xD;
               in Nebraska.)&#xD;
  &#xD;
            5. Patients must have recovered from any toxicity of prior therapy to Grade 1 or less.&#xD;
  &#xD;
            6. ECOG Performance Status of 0-3.&#xD;
  &#xD;
            7. Patients must have an adequate bone marrow reserve (ANC count ≥1,500/mm3, hemoglobin &gt;&#xD;
               8 g/dL, platelet count ≥100,000/mm3).&#xD;
  &#xD;
            8. Patients must have adequate renal and hepatic function with:&#xD;
  &#xD;
                 1. creatinine &lt; 1.5 x institutional upper limit of normal (ULN).&#xD;
  &#xD;
                 2. total bilirubin &lt; 1.5 x ULN (unless due to Gilbert's disease)&#xD;
  &#xD;
                 3. aspartate aminotransferase (AST) or alanine aminotransferase (ALT) &lt;2.5 x ULN&#xD;
  &#xD;
                 4. serum alkaline phosphatase less than 2.5 times the upper limits of normal)&#xD;
  &#xD;
            9. The patient must willingly provide written, informed consent after being informed of&#xD;
               the procedure to be followed, the experimental nature of the therapy, alternatives,&#xD;
               potential benefits, side-effects, risks, and discomforts.&#xD;
  &#xD;
           10. Women of reproductive potential must be non-pregnant and non-nursing and must agree to&#xD;
               employ an effective barrier method of birth control throughout the study and for up to&#xD;
               6 months following treatment.&#xD;
  &#xD;
           11. Women of child-bearing potential must have a negative pregnancy test within 7 days of&#xD;
               initiating study. (Non-child bearing potential is defined as age 55 years or older and&#xD;
               no menses for two years or any age with surgical removal of the uterus and/or both&#xD;
               ovaries).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Any life-threatening illness, medical condition, or organ system dysfunction which, in&#xD;
               the investigator's opinion, could compromise the subject's safety, interfere with the&#xD;
               absorption or metabolism of oral APG-157, or put the study outcomes at undue risk&#xD;
  &#xD;
            2. Immunotherapy, chemotherapy, radiotherapy, or experimental therapy within one full&#xD;
               cycle period before first dose of study drug (i.e., for lomustine 6 weeks, for&#xD;
               temozolomide 4 weeks)&#xD;
  &#xD;
            3. Lactating or pregnant&#xD;
  &#xD;
            4. History of uncontrollable allergic reactions to bevacizumab&#xD;
  &#xD;
            5. Clinically Significant Cardiovascular Disease Defined as follows:&#xD;
  &#xD;
                 -  Inadequately controlled hypertension (i.e., systolic blood pressure (SBP) &gt; 160&#xD;
                    mm Hg and/or diastolic blood pressure (DBP) &gt; 90 mm Hg despite antihypertensive&#xD;
                    therapy)&#xD;
  &#xD;
                 -  History of cerebrovascular accident (CVA) within 6 months&#xD;
  &#xD;
                 -  Myocardial infarction or unstable angina within 6 months&#xD;
  &#xD;
            6. Evidence or history of bleeding diathesis (greater than normal risk of bleeding, i.e.,&#xD;
               Hereditary Hemorrhagic Telangiectasia type I or HHT-1) or coagulopathy in the absence&#xD;
               of therapeutic anti-coagulation or any hemorrhage/bleeding event &gt; Grade 3 within 4&#xD;
               weeks prior to registration. Note: Patients with full-dose anticoagulants are eligible&#xD;
               provided the patient has been on a stable dose for at least 2 weeks&#xD;
  &#xD;
            7. Active wound, a serious or non-healing wound, an active ulcer or untreated bone&#xD;
               fracture.&#xD;
  &#xD;
            8. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess&#xD;
               ≤ 6 months prior to registration.&#xD;
  &#xD;
            9. Major surgical procedure, open biopsy, or significant traumatic injury ≤ 28 days prior&#xD;
               to registration&#xD;
  &#xD;
           10. Any other clinically significant medical disease or condition laboratory abnormality&#xD;
               or psychiatric illness that, in the Investigator's opinion, may interfere with&#xD;
               protocol adherence or a subject's ability to give informed consent&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>19 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Nicole Shonka, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Nebraska</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Joon Uhm, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Mayo Clinic</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Nicole Shonka, MD</last_name>
      <phone>402-559-3881</phone>
      <email>nshonka@unmc.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Apar Ganti, MD</last_name>
      <email>aganti@unmc.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Mayo Clinic</name>
        <address>
          <city>Rochester</city>
          <state>Minnesota</state>
          <zip>55905</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Joon Uhm, MD</last_name>
        <phone>507-284-2120</phone>
        <email>uhm.joon@mayo.edu</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>University of Nebraska Medical Center</name>
        <address>
          <city>Omaha</city>
          <state>Nebraska</state>
          <zip>68198</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Nicole Shonka, MD</last_name>
        <phone>402-559-3881</phone>
        <email>nshonka@unmc.edu</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 9, 2023</study_first_submitted>
    <study_first_submitted_qc>August 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 25, 2023</study_first_posted>
    <last_update_submitted>August 23, 2023</last_update_submitted>
    <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 25, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>APG-157</keyword>
    <keyword>Bevacizumab</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Glioblastoma</mesh_term>
      <mesh_term>Glioma</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06011109
  org study id: AVTA 22-01
  nct id: NCT06011109
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  The goal of this interventional study is to evaluate the efficacy of APG-157 in combination
        with Bevacizumab in subjects with recurrent high-grade glioma. The main questions the study
        aims to answer are:
  
          -  Progression-free and overall survival of patients receiving this combination;
  
          -  Quality of Life (QOL); and
  
          -  Tumor response on imaging
  
        The participants will take APG-157 daily by dissolving two pastilles in their mouth at around
        breakfast, lunch and dinner time (total of six pastilles per day). The pastilles dissolve in
        the mouth.
  
        The participants will continue to receive Bevacizumab as standard of care.
  The goal of this interventional study is to evaluate the efficacy of APG-157 in combination
        with Bevacizumab in subjects with recurrent high-grade glioma who have previously progressed
        on bevacizumab alone. The main questions the study aims to answer are:
  
          -  Progression-free and overall survival of patients receiving this combination;
  
          -  Quality of Life (QOL); and
  
          -  Tumor response on imaging
  
        Additional aims include:
  
          -  characterization of pharmacokinetics (PK) of APG-157 in the presence of bevacizumab; and
  
          -  optionally serum changes in VEGF and HIF-1 alpha, if the study shows preliminary
             indication of efficacy
  
        The participants will take APG-157 daily by dissolving two pastilles in their mouth at around
        breakfast, lunch and dinner time (total of 6 pastilles per day). The pastilles dissolve in
        the mouth.
  
        The participants will continue to receive Bevacizumab and be present for scheduled visits and
        examinations as standard of care.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Progression-free Survival
  time frame: From date of commencement of treatment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months
  description: To evaluate progression-free survival of participants with recurrent high-grade glioma treated with APG-157 and Bevacizumab. Progression of the disease will be assessed using commonly used imaging modality such as Magnetic Resonance Imaging or CT scan.
  measure: Overall Survival
  time frame: From date of commencement of treatment until the date of death from any cause. Duration of assessment will be 12 months from the date of commencement of the treatment.
  description: To evaluate overall survival of participants with recurrent high-grade glioma treated with APG-157 and Bevacizumab
  measure: QOL assessment (EORTC QLQ-C30)
  time frame: Every 8 weeks; from date of commencement of treatment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months
  description: Descriptively examine quality of life (QOL) using EORTC QLQ-C30 (Organization for Research and Treatment in Cancer Quality of Life Questionnaire C30). EORTC QLQ-C30 is a standardized questionnaire that rates function, symptoms and health status from patient perspective using various questions on a scale of 1 - 4 where generally 1 is rated as normal or no issue (not at all) and 4 being the maximum adverse impact being experienced (very much).
  measure: Radiographic studies MRI or CT of the brain
  time frame: Every 8 weeks; from date of commencement of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
  description: To measure tumor size in response to treatment
  measure: Pharmacokinetics (PK) of APG-157
  time frame: At three timepoints: at start of dosing; at end of cycle 1 (each cycle is 28 days); and at end of cycle 2 after start of dosing.
  description: Measure the amount of APG-157 components in the blood in the presence of bevacizumab
  arm group label: APG-157
  arm group type: Experimental
  description: The participants will receive APG-157 daily by taking two pastilles in their mouth at around breakfast, lunch and dinner time (total of six pastilles per day). The pastilles dissolve in the mouth.
  The participants will continue to receive Bevacizumab as standard of care.
  intervention type: Drug
  intervention name: APG-157
  description: The participants will receive APG-157 daily; and continue to receive Bevacizumab as standard of care.
  arm group label: APG-157
  criteria: 
  gender: All
  minimum age: 19 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Nicole Shonka, MD
  role: Principal Investigator
  affiliation: University of Nebraska
  last name: Joon Uhm, MD
  role: Principal Investigator
  affiliation: Mayo Clinic
  last name: Nicole Shonka, MD
  phone: 402-559-3881
  email: nshonka@unmc.edu
  last name: Apar Ganti, MD
  email: aganti@unmc.edu
  facility: 
  contact: 
  facility: 
  contact: 
  country: United States
  responsible party type: Sponsor
  mesh term: Glioblastoma
  mesh term: Glioma
  sharing ipd: No