<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/NCT03032484</url>
  </required_header>
  <id_info>
    <org_study_id>CTMS# 16-0136</org_study_id>
    <nct_id>NCT03032484</nct_id>
  </id_info>
  <brief_title>TVB- 2640 in Combination With Bevacizumab in Patients With First Relapse of High Grade Astrocytoma</brief_title>
  <official_title>A Phase 2 Investigator Initiated Study to Determine the Efficacy and Safety of TVB- 2640 in Combination With Bevacizumab in Patients With First Relapse of High Grade Astrocytoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Texas Health Science Center at San Antonio</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The University of Texas Health Science Center at San Antonio</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>
      Randomized phase 2 study TVB-2640 in combination with Bevacizumab versus Bevacizumab alone.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Eligible patients will be randomized into 2 separate arms:&#xD;
&#xD;
        -  Arm number one will receive Bevacizumab every 2 weeks in combination with TVB-2640 from&#xD;
           day 1 until day 28 of the first cycle.&#xD;
&#xD;
        -  Arm number two will receive Bevacizumab alone every 2 weeks, from on days 1 and 15 of&#xD;
           the first until day 28 of the first cycle.&#xD;
&#xD;
        -  MR-Spectroscopy will be obtained on all patients (both arms) at day 28 of first cycle.&#xD;
&#xD;
        -  Starting on cycle 2 day 1, all patients will converge to a single arm and will continue&#xD;
           to receive bevacizumab every 2 weeks in combination with TVB-2640. Every cycle will last&#xD;
           28 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 18, 2017</start_date>
  <completion_date type="Actual">April 5, 2021</completion_date>
  <primary_completion_date type="Actual">April 4, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression Free Survival at 6 Months (PFS6)</measure>
    <time_frame>6 months</time_frame>
    <description>Survival of participants at 6 months after the start of treatment without their condition becoming any worse. Brain magnetic resonance imaging (MRI) was performed after every even cycle (e.g., C2, C4) during treatment, with tumor response assessed by the investigator for complete response (CR), partial response (PR) and PD according to the Response Assessment in Neuro-oncology (RANO) criteria.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence, Nature and Severity of Adverse Events and Serious Adverse Events, Graded According to NCI - Common Toxicity Criteria for Adverse Events Version (4.03)</measure>
    <time_frame>Up to 6 28-day cycles</time_frame>
    <description>Number of adverse of any nature are reported as well as the number of adverse events that were classed as grade 3-5 on the NCI - Common Toxicity Criteria for Adverse Events</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Metabolic Change Analysis of Tumor Tissue by MRS (Magnetic Resonance Spectroscopy)</measure>
    <time_frame>Cycle 2: approximately 56 days</time_frame>
    <description>The MRI was performed during cycle 2. This procedure was intended to be outsourced, and MRIs performed locally produced inadequate resolution, so no data analysis was obtained from this measure.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Astrocytoma</condition>
  <arm_group>
    <arm_group_label>Bevacizumab and TVB-2640</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Bevacizumab every 2 weeks in combination with TVB-2640 dosed at 100mg/m2 daily (rounded to 50mg tab dose), from day 1 until day 28 of the first cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Bevacizumab for Cycle 1, then Bevacizumab and TVB-2640</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Bevacizumab alone every 2 weeks, on days 1 and 15 until day 28 of the first cycle, and then receive both Bevacizumab and TVB-2640 for the remainder of their participation in this study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <description>Bevacizumab is FDA approved as a treatment for recurrent Glioblastoma following failure of radiation therapy and temozolomide.</description>
    <arm_group_label>Bevacizumab and TVB-2640</arm_group_label>
    <arm_group_label>Bevacizumab for Cycle 1, then Bevacizumab and TVB-2640</arm_group_label>
    <other_name>Avastin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TVB-2640</intervention_name>
    <description>TVB-2640 is a potent and reversible inhibitor of the FASN enzyme. TVB-2640 inhibits the β-ketoacyl reductase (KR) enzymatic activity of the FASN enzyme.</description>
    <arm_group_label>Bevacizumab and TVB-2640</arm_group_label>
    <arm_group_label>Bevacizumab for Cycle 1, then Bevacizumab and TVB-2640</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  At least 18 years of age&#xD;
&#xD;
          -  Ability to understand the purposes and risks of the study and has signed a written&#xD;
             informed consent form approved by the investigator's IRB/Ethics Committee&#xD;
&#xD;
          -  Histologically confirmed high-grade astrocytoma&#xD;
&#xD;
          -  Progression following standard combined modality treatment with radiation and&#xD;
             temozolomide chemotherapy&#xD;
&#xD;
          -  Recovered from reversible toxicities of prior therapy to Grade 0 or Grade 1&#xD;
&#xD;
          -  ECOG Performance Status of 0 to 2&#xD;
&#xD;
          -  Life expectancy of at least 3 months&#xD;
&#xD;
          -  Adequate renal and liver function: AST/ALT ≤ 3 x ULN, Bilirubin ≤ 1.5 times ULN,&#xD;
             Creatinine ≤ ULN&#xD;
&#xD;
          -  Adequate hematologic status (without hematologic support): Hemoglobin ≥ 9 g/dL, ANC ≥&#xD;
             1500 cells/ml, Platelets ≥ 100,000 cells/ml&#xD;
&#xD;
          -  All women of childbearing potential must have a negative serum pregnancy test and male&#xD;
             and female subjects must agree to use effective means of contraception (for example,&#xD;
             surgical sterilization or the use of barrier contraception with either a condom or&#xD;
             diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry&#xD;
             into the study through six months after the last dose.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Receiving warfarin (or other coumarin derivatives) and is unable to switch to low&#xD;
             molecular weight heparin (LMWH) before the first dose of study drug&#xD;
&#xD;
          -  Evidence of acute intracranial or intratumoral hemorrhage either by MRI or CT scan.&#xD;
             Subjects with resolving hemorrhage changes punctuate hemorrhage, or hemosiderin are&#xD;
             eligible&#xD;
&#xD;
          -  Unable to undergo MRI scan (e.g., pacemaker)&#xD;
&#xD;
          -  Received enzyme-inducing anti-epileptic agents within 14 days of study drug (e.g.,&#xD;
             carbamazepine, phenytoin, phenobarbital, primidone)&#xD;
&#xD;
          -  Not recovered to a NCI CTCAE v.4.03 Grade ≤ 1 from AEs (except alopecia and&#xD;
             lymphopenia) due to surgery, antineoplastic agents, investigational drugs, or other&#xD;
             medications that were administered prior to study drug&#xD;
&#xD;
          -  Evidence of wound dehiscence&#xD;
&#xD;
          -  Pregnant or breast-feeding&#xD;
&#xD;
          -  Clinically significant Dry Eye or necessary contact lens use&#xD;
&#xD;
          -  Serious intercurrent illness such as: Hypertension (two or more blood pressure&#xD;
             readings performed at screening of &gt; 150 mmHg systolic or &gt; 100 mmHg diastolic)&#xD;
             despite optimal treatment, Non-healing wound or ulcer, Uncontrolled life threatening&#xD;
             cardiac arrhythmias, Untreated hypothyroidism, Uncontrolled active infection,&#xD;
             Symptomatic congestive heart failure or unstable angina pectoris within 3 months prior&#xD;
             to study drug, Gastrointestinal perforation, abdominal fistula, intra-abdominal&#xD;
             abscess within 1 year&#xD;
&#xD;
          -  Inherited bleeding diathesis or coagulopathy with the risk of bleeding&#xD;
&#xD;
          -  HIV , Hepatitis B or C documented infections&#xD;
&#xD;
          -  Received any of the following prior anticancer therapy: Non-standard radiation therapy&#xD;
             such as brachytherapy, systemic radioisotope therapy (RIT), or intra-operative&#xD;
             radiotherapy (IORT). Note: stereotactic radiosurgery (SRS) is allowed,&#xD;
             Non-antiangiogenic therapy (including investigational agents and small molecular&#xD;
             kinase inhibitors) within 7 days or 5 half-lives, whichever is shorter, prior to the&#xD;
             first dose of study drug, Biologic agents (antibodies, immune modulators, vaccines,&#xD;
             cytokines) within 21 days prior to first dose of study drug, Nitrosoureas or mitomycin&#xD;
             C within 42 days or metronomic/protracted&#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>Andrew Brenner</last_name>
    <role>Principal Investigator</role>
    <affiliation>UT Health San Antonio</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Texas Health Science Center San Antonio at the Cancer Therapy and Research Center</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 24, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <results_first_submitted>July 26, 2021</results_first_submitted>
  <results_first_submitted_qc>June 14, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">June 15, 2023</results_first_posted>
  <last_update_submitted>June 14, 2023</last_update_submitted>
  <last_update_submitted_qc>June 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Astrocytoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bevacizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 16, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/84/NCT03032484/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A cycle 1 randomization to either TVB-2640 plus bevacizumab or bevacizumab monotherapy was conducted in this trial. This randomization was performed for biomarker analysis only and was not intended to be comparative for either safety or efficacy, as it would be unexpected to observe a difference in survival after only one cycle of a study drug.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Bevacizumab and TVB-2640</title>
          <description>Bevacizumab every 2 weeks in combination with TVB-2640 dosed at 100mg/m2 daily (rounded to 50mg tab dose), from day 1 until day 28 of the first cycle.&#xD;
Bevacizumab: Bevacizumab is FDA approved as a treatment for recurrent Glioblastoma following failure of radiation therapy and temozolomide.&#xD;
TVB-2640: TVB-2640 is a potent and reversible inhibitor of the FASN enzyme. TVB-2640 inhibits the β-ketoacyl reductase (KR) enzymatic activity of the FASN enzyme.</description>
        </group>
        <group group_id="P2">
          <title>Bevacizumab</title>
          <description>Bevacizumab alone every 2 weeks, on days 1 and 15 until day 28 of the first cycle.&#xD;
Bevacizumab: Bevacizumab is FDA approved as a treatment for recurrent Glioblastoma following failure of radiation therapy and temozolomide.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study Cycle 1 (C1)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Start of Second Cycle (C2)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="24">All subjects were treated with TVB-2640 and Bevacizumab following C1, there was no continuation of Bevacizumab treatment alone, and efficacy and safety data were assessed for the aggregated group.</participants>
                <participants group_id="P2" count="0">All subjects were treated with TVB-2640 and Bevacizumab following C1. No subject progressed to Bevacizumab treatment alone, all were treated with TVB/Bev combination.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Bevacizumab and TVB-2640</title>
          <description>Bevacizumab every 2 weeks in combination with TVB-2640 dosed at 100mg/m2 daily (rounded to 50mg tab dose), from day 1 until day 28 of the first cycle.&#xD;
Bevacizumab: Bevacizumab is FDA approved as a treatment for recurrent Glioblastoma following failure of radiation therapy and temozolomide.&#xD;
TVB-2640: TVB-2640 is a potent and reversible inhibitor of the FASN enzyme. TVB-2640 inhibits the β-ketoacyl reductase (KR) enzymatic activity of the FASN enzyme.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="25"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61" lower_limit="37" upper_limit="69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Progression Free Survival at 6 Months (PFS6)</title>
        <description>Survival of participants at 6 months after the start of treatment without their condition becoming any worse. Brain magnetic resonance imaging (MRI) was performed after every even cycle (e.g., C2, C4) during treatment, with tumor response assessed by the investigator for complete response (CR), partial response (PR) and PD according to the Response Assessment in Neuro-oncology (RANO) criteria.</description>
        <time_frame>6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bevacizumab and TVB-2640</title>
            <description>Bevacizumab every 2 weeks in combination with TVB-2640 dosed at 100mg/m2 daily (rounded to 50mg tab dose), from day 1 until day 28 of the first cycle.&#xD;
Bevacizumab: Bevacizumab is FDA approved as a treatment for recurrent Glioblastoma following failure of radiation therapy and temozolomide.&#xD;
TVB-2640: TVB-2640 is a potent and reversible inhibitor of the FASN enzyme. TVB-2640 inhibits the β-ketoacyl reductase (KR) enzymatic activity of the FASN enzyme.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival at 6 Months (PFS6)</title>
          <description>Survival of participants at 6 months after the start of treatment without their condition becoming any worse. Brain magnetic resonance imaging (MRI) was performed after every even cycle (e.g., C2, C4) during treatment, with tumor response assessed by the investigator for complete response (CR), partial response (PR) and PD according to the Response Assessment in Neuro-oncology (RANO) criteria.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence, Nature and Severity of Adverse Events and Serious Adverse Events, Graded According to NCI - Common Toxicity Criteria for Adverse Events Version (4.03)</title>
        <description>Number of adverse of any nature are reported as well as the number of adverse events that were classed as grade 3-5 on the NCI - Common Toxicity Criteria for Adverse Events</description>
        <time_frame>Up to 6 28-day cycles</time_frame>
        <population>Subject who received TVB-2640 and Bevacizumab or Bevacizumab alone</population>
        <group_list>
          <group group_id="O1">
            <title>Bevacizumab and TVB-2640</title>
            <description>Bevacizumab every 2 weeks in combination with TVB-2640 dosed at 100mg/m2 daily (rounded to 50mg tab dose), from day 1 until day 28 of the first cycle.&#xD;
Bevacizumab: Bevacizumab is FDA approved as a treatment for recurrent Glioblastoma following failure of radiation therapy and temozolomide.&#xD;
TVB-2640: TVB-2640 is a potent and reversible inhibitor of the FASN enzyme. TVB-2640 inhibits the β-ketoacyl reductase (KR) enzymatic activity of the FASN enzyme.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence, Nature and Severity of Adverse Events and Serious Adverse Events, Graded According to NCI - Common Toxicity Criteria for Adverse Events Version (4.03)</title>
          <description>Number of adverse of any nature are reported as well as the number of adverse events that were classed as grade 3-5 on the NCI - Common Toxicity Criteria for Adverse Events</description>
          <population>Subject who received TVB-2640 and Bevacizumab or Bevacizumab alone</population>
          <units>number of events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Number of adverse events any grade</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="183"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Adverse events grade 3-5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Metabolic Change Analysis of Tumor Tissue by MRS (Magnetic Resonance Spectroscopy)</title>
        <description>The MRI was performed during cycle 2. This procedure was intended to be outsourced, and MRIs performed locally produced inadequate resolution, so no data analysis was obtained from this measure.</description>
        <time_frame>Cycle 2: approximately 56 days</time_frame>
        <population>Data were not evaluable for this measure, since MRI resolution was inadequate</population>
        <group_list>
          <group group_id="O1">
            <title>Bevacizumab and TVB-2640</title>
            <description>Bevacizumab every 2 weeks in combination with TVB-2640 dosed at 100mg/m2 daily (rounded to 50mg tab dose), from day 1 until day 28 of the first cycle.&#xD;
Bevacizumab: Bevacizumab is FDA approved as a treatment for recurrent Glioblastoma following failure of radiation therapy and temozolomide.&#xD;
TVB-2640: TVB-2640 is a potent and reversible inhibitor of the FASN enzyme. TVB-2640 inhibits the β-ketoacyl reductase (KR) enzymatic activity of the FASN enzyme.</description>
          </group>
        </group_list>
        <measure>
          <title>Metabolic Change Analysis of Tumor Tissue by MRS (Magnetic Resonance Spectroscopy)</title>
          <description>The MRI was performed during cycle 2. This procedure was intended to be outsourced, and MRIs performed locally produced inadequate resolution, so no data analysis was obtained from this measure.</description>
          <population>Data were not evaluable for this measure, since MRI resolution was inadequate</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from study enrollment for up to six cycles (28 days each) or until there is evidence of significant treatment related toxicity or progressive disease. Subject were assessed for adverse events which occurred after the start of treatment until 30 days after study drug discontinuation or subsequent cancer therapy was initiated. Adverse events were collected over a 1.5 year period.</time_frame>
      <desc>Bevacizumab during cycle 1 and Bevacizumab and TVB-2640 were combined as pre-specified in the study protocol</desc>
      <group_list>
        <group group_id="E1">
          <title>Bevacizumab and TVB-2640</title>
          <description>Bevacizumab every 2 weeks in combination with TVB-2640 dosed at 100mg/m2 daily (rounded to 50mg tab dose), from day 1 until day 28 of the first cycle.&#xD;
Bevacizumab: Bevacizumab is FDA approved as a treatment for recurrent Glioblastoma following failure of radiation therapy and temozolomide.&#xD;
TVB-2640: TVB-2640 is a potent and reversible inhibitor of the FASN enzyme. TVB-2640 inhibits the β-ketoacyl reductase (KR) enzymatic activity of the FASN enzyme.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <description>Right lower extremity deep vein thrombosis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Wound infection</sub_title>
                <description>Perirectal abcess</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Aphasia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Limb edema</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="21" subjects_affected="13" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Dry Eye</sub_title>
                <counts group_id="E1" events="13" subjects_affected="12" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dysphasia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="9" subjects_affected="7" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Elevated ALT/AST</sub_title>
                <description>Elevated liver enzymes</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle weakness</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Parestheisa</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Cognitive Disturbance</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Aphasia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Increased Creatinine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Palmar plantar erythrodysesthesia syndrome</sub_title>
                <counts group_id="E1" events="41" subjects_affected="18" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Mucositis</sub_title>
                <counts group_id="E1" events="22" subjects_affected="15" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>alopecia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dry Skin</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Pruritis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Andrew Brenner, MD</name_or_title>
      <organization>University of Texas Health San Antonio</organization>
      <phone>210-562-4090</phone>
      <email>brennera@uthscsa.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03032484
org study id: CTMS# 16-0136
nct id: NCT03032484
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Randomized phase 2 study TVB-2640 in combination with Bevacizumab versus Bevacizumab alone.
Eligible patients will be randomized into 2 separate arms:

        -  Arm number one will receive Bevacizumab every 2 weeks in combination with TVB-2640 from
           day 1 until day 28 of the first cycle.

        -  Arm number two will receive Bevacizumab alone every 2 weeks, from on days 1 and 15 of
           the first until day 28 of the first cycle.

        -  MR-Spectroscopy will be obtained on all patients (both arms) at day 28 of first cycle.

        -  Starting on cycle 2 day 1, all patients will converge to a single arm and will continue
           to receive bevacizumab every 2 weeks in combination with TVB-2640. Every cycle will last
           28 days.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression Free Survival at 6 Months (PFS6)
time frame: 6 months
description: Survival of participants at 6 months after the start of treatment without their condition becoming any worse. Brain magnetic resonance imaging (MRI) was performed after every even cycle (e.g., C2, C4) during treatment, with tumor response assessed by the investigator for complete response (CR), partial response (PR) and PD according to the Response Assessment in Neuro-oncology (RANO) criteria.
measure: Incidence, Nature and Severity of Adverse Events and Serious Adverse Events, Graded According to NCI - Common Toxicity Criteria for Adverse Events Version (4.03)
time frame: Up to 6 28-day cycles
description: Number of adverse of any nature are reported as well as the number of adverse events that were classed as grade 3-5 on the NCI - Common Toxicity Criteria for Adverse Events
measure: Metabolic Change Analysis of Tumor Tissue by MRS (Magnetic Resonance Spectroscopy)
time frame: Cycle 2: approximately 56 days
description: The MRI was performed during cycle 2. This procedure was intended to be outsourced, and MRIs performed locally produced inadequate resolution, so no data analysis was obtained from this measure.
arm group label: Bevacizumab and TVB-2640
arm group type: Experimental
description: Bevacizumab every 2 weeks in combination with TVB-2640 dosed at 100mg/m2 daily (rounded to 50mg tab dose), from day 1 until day 28 of the first cycle.
arm group label: Bevacizumab for Cycle 1, then Bevacizumab and TVB-2640
arm group type: Experimental
description: Bevacizumab alone every 2 weeks, on days 1 and 15 until day 28 of the first cycle, and then receive both Bevacizumab and TVB-2640 for the remainder of their participation in this study.
intervention type: Drug
intervention name: Bevacizumab
description: Bevacizumab is FDA approved as a treatment for recurrent Glioblastoma following failure of radiation therapy and temozolomide.
arm group label: Bevacizumab and TVB-2640
arm group label: Bevacizumab for Cycle 1, then Bevacizumab and TVB-2640
other name: Avastin
intervention type: Drug
intervention name: TVB-2640
description: TVB-2640 is a potent and reversible inhibitor of the FASN enzyme. TVB-2640 inhibits the β-ketoacyl reductase (KR) enzymatic activity of the FASN enzyme.
arm group label: Bevacizumab and TVB-2640
arm group label: Bevacizumab for Cycle 1, then Bevacizumab and TVB-2640
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Andrew Brenner
role: Principal Investigator
affiliation: UT Health San Antonio
facility: 
country: United States
responsible party type: Sponsor
mesh term: Astrocytoma
mesh term: Bevacizumab
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 