<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/NCT03250299</url>
  </required_header>
  <id_info>
    <org_study_id>ABTC 1601</org_study_id>
    <secondary_id>CDI-CS-004</secondary_id>
    <secondary_id>IRB00131687</secondary_id>
    <nct_id>NCT03250299</nct_id>
  </id_info>
  <brief_title>Microtubule-Targeted Agent BAL101553 and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma</brief_title>
  <official_title>Phase I Study to Determine the Safety and Tolerability of the Oral Microtubule Destabilizer BAL101553 in Combination With Standard Radiation in Patients With MGMT Promoter Unmethylated Newly Diagnosed Glioblastoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Basilea Pharmaceutica</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Basilea Pharmaceutica</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 phase I trial studies the side effects and best dose of microtubule-targeted agent&#xD;
      BAL101553 when given together with radiation therapy in treating patients with newly&#xD;
      diagnosed glioblastoma. Drugs used in chemotherapy, such as microtubule-targeted agent&#xD;
      BAL101553, work in different ways to stop the growth of tumor cells, either by killing the&#xD;
      cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy&#xD;
      uses high-energy x-rays to kill tumor cells and shrink tumors. Giving microtubule-targeted&#xD;
      agent BAL101553 and radiation therapy may work better in treating patients with glioblastoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the maximum tolerated dose of microtubule-targeted agent BAL101553&#xD;
      (BAL101553) in combination with standard radiation in patients with newly diagnosed MGMT&#xD;
      promoter unmethylated glioblastoma (GBM).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To estimate safety and tolerability of the combination of BAL101553 in combination with&#xD;
      standard radiation in patients with newly diagnosed MGMT promoter unmethylated GBM.&#xD;
&#xD;
      II. To determine overall and progression-free survival. III. To assess the pharmacokinetics&#xD;
      of BAL101553 and BAL27862. IV. To explore expression of biomarkers, including BubR1, stathmin&#xD;
      and EB1 at baseline (exploratory biomarkers).&#xD;
&#xD;
      OUTLINE: This is a dose escalation study of the microtubule-targeted agent BAL101553.&#xD;
&#xD;
      Patients receive microtubule-targeted agent BAL101553 orally (PO) once daily (QD) on days&#xD;
      1-42 and undergo concomitant standard radiation therapy 5 days per week for 6 weeks in the&#xD;
      absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 30 days, and then every 2&#xD;
      months for 2 years and then every 6 months thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Due to the National Cancer Institute's (NCI)-mandated termination of the Adult Brain Tumor&#xD;
    Consortium which was conducting the study&#xD;
  </why_stopped>
  <start_date type="Actual">June 7, 2017</start_date>
  <completion_date type="Actual">August 24, 2022</completion_date>
  <primary_completion_date type="Actual">June 3, 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Tolerated Dose (MTD)</measure>
    <time_frame>up to 10 weeks</time_frame>
    <description>Number of Dose limited Toxicities per dose level. ANC &lt; 500/mm3; Platelets &lt; 25K; Febrile neutropenia; any event which prevents 80% administration of planned BAL101553 dose; &gt;/= gr 2 CNS ischemia; &gt;/= gr 2 neurological toxicities interfering with AODL not resolved within 2wks; gr 3/4 non-hematological, non-CNS toxicities with expections</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects with Grade 3 and Grade 4 AEs</measure>
    <time_frame>up to 10 weeks</time_frame>
    <description>CTC AE 4.0 / 5.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>initial diagnosis to date of death - up to 2 years</time_frame>
    <description>Median time of survival along with 95% confidence interval</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>initial diagnosis to date of progression - up to 2 years</time_frame>
    <description>Median time of progression-free survival along with 95% confidence interval</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration</measure>
    <time_frame>Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post dose on days 1 and 22</time_frame>
    <description>PK of microtubule-targeted agent BAL101553 and BAL27862</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of Maximum Plasma Concentraion</measure>
    <time_frame>Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post dose on days 1 and 22</time_frame>
    <description>PK of microtubule-targeted agent BAL101553 and BAL27862</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration-time Curve (AUC)</measure>
    <time_frame>Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post dose on days 1 and 22</time_frame>
    <description>PK of microtubule-targeted agent BAL101553 and BAL27862</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Half-life</measure>
    <time_frame>Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post dose on days 1 and 22</time_frame>
    <description>PK of microtubule-targeted agent BAL101553 and BAL27862</description>
  </other_outcome>
  <other_outcome>
    <measure>Clearance and Volume</measure>
    <time_frame>Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post dose on days 1 and 22</time_frame>
    <description>PK of microtubule-targeted agent BAL101553 and BAL27862</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Glioblastoma</condition>
  <condition>MGMT-Unmethylated Glioblastoma</condition>
  <arm_group>
    <arm_group_label>Dose Finding</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fixed 3+3 dose escalation of BAL101553 (7 days per week), combined with RT days 1-5 for 6 weeks followed by 4 week rest.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Microtubule-Targeted Agent BAL101553</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Dose Finding</arm_group_label>
    <other_name>BAL101553, Microtubule-targeted Agent BAL101553</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiation Therapy</intervention_name>
    <description>Undergo radiation therapy</description>
    <arm_group_label>Dose Finding</arm_group_label>
    <other_name>Cancer Radiotherapy, Irradiate, irradiated, irradiation, RADIATION, Radiation, radiation therapy, Radiation Therapy, Radiotherapeutics, radiotherapy, Radiotherapy, RT, Therapy, Radiation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Dose Finding</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharmacological Study</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Dose Finding</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have histologically-proven GBM&#xD;
&#xD;
          -  Patients must have recovered from the immediate post-operative period&#xD;
&#xD;
          -  Patients must have tumor MGMT methylation status of unmethylated as determined by&#xD;
             local pathologist using a Clinical Laboratory Improvement Act (CLIA)-approved&#xD;
             diagnostic test; results of routinely-used methods for MGMT methylation testing (e.g.&#xD;
             methylation-specific [MS]- polymerase chain reaction [PCR] or quantitative PCR) are&#xD;
             acceptable&#xD;
&#xD;
          -  Patients must be able to undergo magnetic resonance imaging (MRI) of the brain with&#xD;
             gadolinium&#xD;
&#xD;
          -  Patients must not have received prior radiation therapy (RT), chemotherapy,&#xD;
             immunotherapy or therapy with a biologic agent (including immunotoxins,&#xD;
             immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins,&#xD;
             tumor-infiltrating lymphocytes, lymphokine-activated killer cells, or gene therapy),&#xD;
             or hormonal therapy for their brain tumor; glucocorticoid therapy is allowed&#xD;
&#xD;
          -  Patients must have a tumor tissue form indicating availability of archived tissue from&#xD;
             initial resection at diagnosis of GBM, completed and signed by a pathologist&#xD;
&#xD;
          -  Patients must have a Karnofsky performance status &gt;= 60% (i.e. the patient must be&#xD;
             able to care for himself/herself with occasional help from others)&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1,500/mcL&#xD;
&#xD;
          -  Platelets &gt;= 100,000/mcL&#xD;
&#xD;
          -  Hemoglobin &gt;= 9 g/dL&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x institutional upper limit of normal (ULN), unless the patient&#xD;
             has known Gilbert's syndrome&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase&#xD;
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])&#xD;
             =&lt; 2.5 x ULN&#xD;
&#xD;
          -  Creatinine =&lt; 1.5 x ULN&#xD;
&#xD;
          -  Creatinine clearance &gt;= 60 mL/min/1.73 m^2 for patients with creatinine levels &gt; ULN&#xD;
&#xD;
          -  Activated partial thromboplastin time (APTT)/partial thromboplastin time (PTT) =&lt; 1.5&#xD;
             x ULN&#xD;
&#xD;
          -  Sodium &gt;= 130 mmol/L&#xD;
&#xD;
          -  Patients must be able to provide written informed consent&#xD;
&#xD;
          -  Patients must have baseline MRI performed within the 21 days prior to starting&#xD;
             treatment&#xD;
&#xD;
          -  Women of childbearing potential must have a negative serum pregnancy test within 72&#xD;
             hours prior to the first dose of BAL101553; women of childbearing potential must agree&#xD;
             to use highly-effective contraceptive methods for the duration of study participation&#xD;
             and for an additional 90 days after the last dose of study drug; highly-effective&#xD;
             contraceptive methods include male or female sterilization (bilateral tubal occlusion&#xD;
             or vasectomy); intrauterine device (IUD); combined (estrogen- and&#xD;
             progesterone-containing) hormonal contraception (oral, vaginal ring or transdermal&#xD;
             patch) with an ethinylestradiol dose of at least 30 ug, plus use of male condoms&#xD;
             (preferably with spermicides), female condoms, a female diaphragm or a cervical cap;&#xD;
             or total sexual abstinence; should a woman become pregnant or suspect she is pregnant&#xD;
             while participating in this study, she should inform her treating physician&#xD;
             immediately; male patients must agree not to donate sperm from the first dose of study&#xD;
             drug until 90 days after the end of treatment; male patients, without a vasectomy and&#xD;
             with a partner of childbearing potential, must agree to use condoms during the study&#xD;
             and for at least 90 days after the end of treatment; the patient should be instructed&#xD;
             that their female partner should use another form of contraception for the duration of&#xD;
             the study and continue this use for at least 90 days after the last dose of study drug&#xD;
&#xD;
          -  Patients must have no concurrent malignancy except curatively treated basal or&#xD;
             squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or&#xD;
             bladder; patients with prior malignancies must be disease-free for &gt;= 5 years&#xD;
&#xD;
          -  Patients must be maintained on a stable corticosteroid regimen (no increase for 5&#xD;
             days) prior to the start of treatment&#xD;
&#xD;
          -  Patients must be able to swallow whole capsules&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients receiving any other investigational agents&#xD;
&#xD;
          -  Patients with a history of allergic reactions attributed to compounds of similar&#xD;
             chemical or biologic composition to BAL101553&#xD;
&#xD;
          -  Patients on drugs that are strong inhibitors and/or inducers of CYP2C9, CYP2C19 or&#xD;
             CYP3A4 (including enzyme-inducing anti-epileptic drugs [EIAEDs]), are not eligible for&#xD;
             treatment under this protocol; patients taking non-EIAEDs are permitted to take part&#xD;
             in the study; patients previously treated with any of the prohibited concomitant&#xD;
             medications listed above may be enrolled if they have been off of the medication for&#xD;
             &gt;= 10 days prior to the first dose of BAL101553&#xD;
&#xD;
          -  Patients may not be on coumarin anti-coagulants (warfarin, etc.); heparin,&#xD;
             low-molecular weight heparin (LMWH), or other antithrombotic medications are permitted&#xD;
&#xD;
          -  Patients with gastrointestinal disease, or those who have had a procedure that is&#xD;
             expected to interfere with the oral absorption or tolerance of BAL101553 (e.g.,&#xD;
             functionally-relevant gastrointestinal obstruction, or frequent vomiting unresolved&#xD;
             upon anti-emetic supportive care)&#xD;
&#xD;
          -  Patients with peripheral neuropathy &gt;= Common Terminology Criteria for Adverse Events&#xD;
             (CTCAE) grade 2&#xD;
&#xD;
          -  Patients with ataxia &gt;= CTCAE grade 2&#xD;
&#xD;
          -  Patients with known acute or chronic hepatitis B or hepatitis C infection \&#xD;
&#xD;
          -  Patients with systolic blood pressure (SBP) &gt;= 140 mmHg or diastolic blood pressure&#xD;
             (DBP) &gt;= 90 mmHg at the screening visit are ineligible; patients with an initial&#xD;
             clinic blood pressure (BP) &gt;= 140/90 mmHg may be included if SBP &lt; 140 mmHg and DBP &lt;&#xD;
             90 mmHg is confirmed in two subsequent BP measurements on the same day&#xD;
&#xD;
          -  Patients with blood pressure (BP) combination treatment with more than two&#xD;
             antihypertensive medications are ineligible&#xD;
&#xD;
          -  Significant cardiac disease or abnormality, including any one of the following:&#xD;
&#xD;
               -  Left ventricular ejection fraction &lt; 50% at screening (assessed by&#xD;
                  echocardiography, cardiac MRI or multigated acquisition [MUGA])&#xD;
&#xD;
               -  Corrected QT Fridericia's correction formula (QTcF) &gt; 470 ms on screening&#xD;
                  electrocardiogram (ECG), or a clinically-relevant ECG abnormality&#xD;
&#xD;
               -  Congenital long QT syndrome&#xD;
&#xD;
               -  History of sustained ventricular tachycardia, ventricular fibrillation, or&#xD;
                  torsades de pointes&#xD;
&#xD;
               -  Presence of atrial fibrillation with tachyarrhythmia (ventricular response rate &gt;&#xD;
                  100 beats per minute [bpm])&#xD;
&#xD;
               -  Bradycardia (heart rate &lt; 50 bpm)&#xD;
&#xD;
               -  Complete left bundle branch block.&#xD;
&#xD;
               -  Bifascicular block (complete right bundle branch block and anterior or posterior&#xD;
                  left hemiblock)&#xD;
&#xD;
               -  Myocardial infarction, acute coronary syndrome (including unstable angina),&#xD;
                  coronary revascularization procedures, or coronary arterial bypass grafting&#xD;
                  within the 6 months prior to starting study drug&#xD;
&#xD;
               -  Cardiac troponin (either troponin T or troponin I) &gt; ULN&#xD;
&#xD;
               -  Congestive heart failure of New York Heart Association class III or IV&#xD;
&#xD;
               -  Unstable angina pectoris&#xD;
&#xD;
          -  Patients with uncontrolled intercurrent illness including, but not limited to, ongoing&#xD;
             or active infection or psychiatric illness/social situations that would limit&#xD;
             compliance with study requirements, are ineligible&#xD;
&#xD;
          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if&#xD;
             the mother is treated with BAL101553&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral&#xD;
             therapy are ineligible&#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>Matthias Holdhoff, MD</last_name>
    <role>Study Chair</role>
    <affiliation>National Cancer Institute (NCI)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UAB Comprehensive Cancer Center</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294-3410</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Hospital</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest University Comprehensive Cancer Center</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Taussig Cancer Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Abrams Cancer Center of the University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hillman Cancer Center at University of Pittsburgh Cancer Institute</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>July 28, 2017</study_first_submitted>
  <study_first_submitted_qc>August 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>September 30, 2022</last_update_submitted>
  <last_update_submitted_qc>September 30, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 3, 2022</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>Glioblastoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lisavanbulin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>June 2, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03250299
org study id: ABTC 1601
secondary id: CDI-CS-004
secondary id: IRB00131687
nct id: NCT03250299
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase I trial studies the side effects and best dose of microtubule-targeted agent
      BAL101553 when given together with radiation therapy in treating patients with newly
      diagnosed glioblastoma. Drugs used in chemotherapy, such as microtubule-targeted agent
      BAL101553, work in different ways to stop the growth of tumor cells, either by killing the
      cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy
      uses high-energy x-rays to kill tumor cells and shrink tumors. Giving microtubule-targeted
      agent BAL101553 and radiation therapy may work better in treating patients with glioblastoma.
PRIMARY OBJECTIVES:

      I. To determine the maximum tolerated dose of microtubule-targeted agent BAL101553
      (BAL101553) in combination with standard radiation in patients with newly diagnosed MGMT
      promoter unmethylated glioblastoma (GBM).

      SECONDARY OBJECTIVES:

      I. To estimate safety and tolerability of the combination of BAL101553 in combination with
      standard radiation in patients with newly diagnosed MGMT promoter unmethylated GBM.

      II. To determine overall and progression-free survival. III. To assess the pharmacokinetics
      of BAL101553 and BAL27862. IV. To explore expression of biomarkers, including BubR1, stathmin
      and EB1 at baseline (exploratory biomarkers).

      OUTLINE: This is a dose escalation study of the microtubule-targeted agent BAL101553.

      Patients receive microtubule-targeted agent BAL101553 orally (PO) once daily (QD) on days
      1-42 and undergo concomitant standard radiation therapy 5 days per week for 6 weeks in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days, and then every 2
      months for 2 years and then every 6 months thereafter.
allocation: N/A
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD)
time frame: up to 10 weeks
description: Number of Dose limited Toxicities per dose level. ANC < 500/mm3; Platelets < 25K; Febrile neutropenia; any event which prevents 80% administration of planned BAL101553 dose; >/= gr 2 CNS ischemia; >/= gr 2 neurological toxicities interfering with AODL not resolved within 2wks; gr 3/4 non-hematological, non-CNS toxicities with expections
measure: Proportion of subjects with Grade 3 and Grade 4 AEs
time frame: up to 10 weeks
description: CTC AE 4.0 / 5.0
measure: Overall Survival
time frame: initial diagnosis to date of death - up to 2 years
description: Median time of survival along with 95% confidence interval
measure: Progression Free Survival
time frame: initial diagnosis to date of progression - up to 2 years
description: Median time of progression-free survival along with 95% confidence interval
measure: Maximum Plasma Concentration
time frame: Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post dose on days 1 and 22
description: PK of microtubule-targeted agent BAL101553 and BAL27862
measure: Time of Maximum Plasma Concentraion
time frame: Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post dose on days 1 and 22
description: PK of microtubule-targeted agent BAL101553 and BAL27862
measure: Area Under the Concentration-time Curve (AUC)
time frame: Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post dose on days 1 and 22
description: PK of microtubule-targeted agent BAL101553 and BAL27862
measure: Half-life
time frame: Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post dose on days 1 and 22
description: PK of microtubule-targeted agent BAL101553 and BAL27862
measure: Clearance and Volume
time frame: Pre-dose, 0.5, 1, 2, 4, 6, and 24 hours post dose on days 1 and 22
description: PK of microtubule-targeted agent BAL101553 and BAL27862
arm group label: Dose Finding
arm group type: Experimental
description: Fixed 3+3 dose escalation of BAL101553 (7 days per week), combined with RT days 1-5 for 6 weeks followed by 4 week rest.
intervention type: Drug
intervention name: Microtubule-Targeted Agent BAL101553
description: Given PO
arm group label: Dose Finding
other name: BAL101553, Microtubule-targeted Agent BAL101553
intervention type: Radiation
intervention name: Radiation Therapy
description: Undergo radiation therapy
arm group label: Dose Finding
other name: Cancer Radiotherapy, Irradiate, irradiated, irradiation, RADIATION, Radiation, radiation therapy, Radiation Therapy, Radiotherapeutics, radiotherapy, Radiotherapy, RT, Therapy, Radiation
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Dose Finding
intervention type: Other
intervention name: Pharmacological Study
description: Correlative studies
arm group label: Dose Finding
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Matthias Holdhoff, MD
role: Study Chair
affiliation: National Cancer Institute (NCI)
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Glioblastoma
mesh term: Lisavanbulin
sharing ipd: No
submitted: June 2, 2023