<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/NCT03020602</url>
  </required_header>
  <id_info>
    <org_study_id>IRB-38514</org_study_id>
    <secondary_id>NCI-2016-01973</secondary_id>
    <secondary_id>BRN0035</secondary_id>
    <nct_id>NCT03020602</nct_id>
  </id_info>
  <brief_title>BPM31510 in Treating Patients With Recurrent High-Grade Glioma Previously Treated With Bevacizumab</brief_title>
  <official_title>A Phase I Study of BPM31510 Plus Vitamin K in Subjects With High-Grade Glioma That Has Recurred on a Bevacizumab Containing Regimen</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Seema Nagpal</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies the side effects and best dose of ubidecarenone injectable&#xD;
      nanosuspension (BPM31510) in treating patients with high-grade glioma (anaplastic astrocytoma&#xD;
      or glioblastoma) that has come back and have been previously treated with bevacizumab.&#xD;
      BPM31510 may stop the growth of tumor cells by blocking some of the enzymes needed for cell&#xD;
      growth.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Objective:&#xD;
&#xD;
        -  Assess the safety and tolerability of BPM31510 plus vitamin K in subjects with&#xD;
           high-grade glioma(HGG), defined as anaplastic astrocytoma (AA) or glioblastoma (GB) that&#xD;
           has recurred on a BEV containing regimen.&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
        -  To evaluate plasma pharmacokinetics (PK) when BPM31510 plus vitamin K is given to&#xD;
           subjects with HGG recurrent on a BEV containing regimen.&#xD;
&#xD;
      Exploratory Objectives:&#xD;
&#xD;
        -  Estimate the overall survival in subjects with HGG recurrent on a BEV containing regimen&#xD;
           from the 1st day of infusion of BPM31510 plus vitamin K to death.&#xD;
&#xD;
        -  To evaluate the effects of BPM31510 plus vitamin K on shifting HGG metabolism to aerobic&#xD;
           respiration by PET imaging.&#xD;
&#xD;
        -  To evaluate the effects of BPM1510 plus vitamin K on MRI imaging by Response Assessment&#xD;
           in Neuro Oncology (RANO) criteria [specifically progression free survival (PFS) and&#xD;
           response rate (RR)].&#xD;
&#xD;
        -  To evaluate plasma pharmacodynamics (PD) when BPM31510 plus vitamin K is given to&#xD;
           subjects with HGG recurrent on a BEV containing regimen.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 4, 2017</start_date>
  <completion_date type="Actual">June 26, 2021</completion_date>
  <primary_completion_date type="Actual">April 4, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of patients with dose-limiting toxicities defined as thrombocytopenia &gt;= grade 3, hemorrhage &gt;= grade 3, and INR elevation &gt;= grade 2 assessed by CTCAE v4.03</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Will be tabulated at each dose, along with the result of the pooled adjacent violators algorithm as implemented in the Modified Toxicity Probability Interval (equal weights, and the weighted mean solver).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) version (v)4.03</measure>
    <time_frame>Up to 30 days after last dose of BPM3150</time_frame>
    <description>Will be tabulated separately for each dose cohort, by Medical Dictionary for Regulatory Activities (MedDRA) major organ system and severity.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Brain tumor metabolism as measured by PET</measure>
    <time_frame>Up to 8 weeks</time_frame>
    <description>Standardized uptake value (SUV) of the HGG will be measured. SUV is the standard PET measure.</description>
  </other_outcome>
  <other_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>From the date of BPM31510 initiation to death, assessed for up to 3 years</time_frame>
    <description>Kaplan-Meier survival estimates for OS will be presented for data at the maximum tolerated dose, with a 95% confidence interval using Greenwood's formula at 3.5 months and 7 months.</description>
  </other_outcome>
  <other_outcome>
    <measure>PFS assessed by RANO criteria</measure>
    <time_frame>Up to 3 years</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Response rate assessed by RANO criteria</measure>
    <time_frame>Up to 3 years</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Gliosarcoma</condition>
  <condition>Recurrent Glioblastoma</condition>
  <condition>Astrocytoma of Brain</condition>
  <condition>Glioblastoma</condition>
  <arm_group>
    <arm_group_label>Treatment (BPM31510)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive ubidecarenone injectable nanosuspension IV over 72 hours twice weekly. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (BPM31510)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharmacological Study</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (BPM31510)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ubidecarenone Injectable Nanosuspension</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (BPM31510)</arm_group_label>
    <other_name>BP31510</other_name>
    <other_name>Coenzyme Q10 Injectable Nanosuspension</other_name>
    <other_name>Ubiquinone Injectable Nanosuspension</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be ≥ 18 years of age&#xD;
&#xD;
          -  Have a life expectancy ≥ 6 weeks&#xD;
&#xD;
          -  Have a Karnofsky Performance Score (KPS) ≥ 60&#xD;
&#xD;
          -  Have pathologically proven GB, gliosarcoma (WHO IV), or anaplastic astrocytoma (WHO&#xD;
             III) in recurrence after treatment with bevacizumab&#xD;
&#xD;
          -  Be at least 14 days from the last administration of bevacizumab&#xD;
&#xD;
          -  Be at least 28 days from last administration of cytotoxic chemotherapy or other&#xD;
             investigational agent&#xD;
&#xD;
          -  Have received radiation therapy with concurrent temozolomide. Total radiation dosage&#xD;
             can range from 5400 to 6000 cGy administered in daily fractions of 150 to 200 cGy over&#xD;
             6 weeks, or the equivalent in a hypofractionated protocol (for example, 4000cGy in 15&#xD;
             fractions or 2500cGy in 5 fractions). Patients who are MGMT negative do not need to&#xD;
             have received temozolomide.&#xD;
&#xD;
          -  Have adequate organ and marrow function as follows (all required):&#xD;
&#xD;
               -  ANC ≥ 1500 mm3&#xD;
&#xD;
               -  Platelets ≥ 100,000/mm3&#xD;
&#xD;
               -  Hemoglobin ≥ 9 g/dL&#xD;
&#xD;
               -  Serum creatinine ≤ 1.8 mg/dL or creatinine clearance &gt; 50 mL/min Bilirubin ≤ 1.5&#xD;
                  mg/dL&#xD;
&#xD;
               -  Alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)&#xD;
&#xD;
               -  Aspartate transaminase (AST) ≤ 2.5 x ULN&#xD;
&#xD;
               -  Prothrombin time (PT) ≤ 1.5 x ULN&#xD;
&#xD;
               -  International Normalized Ratio (INR) ≤ 1.5 x ULN&#xD;
&#xD;
               -  Partial thromboplastin time (PTT) ≤ 1.5 x ULN&#xD;
&#xD;
          -  Subjects of childbearing potential must agree to use hormonal or barrier birth control&#xD;
             with spermicidal gel to avoid pregnancy during the study&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has a history of spontaneous or tumor related cerebral hemorrhage; or has cerebral&#xD;
             hemorrhage as determined by the screening FDG PET CT and MRI. This does not include&#xD;
             stable post operative blood products seen on a gradient echo MRI sequence.&#xD;
&#xD;
          -  Has the any of the following cardiac history:&#xD;
&#xD;
               -  Active heart disease including myocardial infarction within previous 3 months&#xD;
&#xD;
               -  Symptomatic coronary artery disease&#xD;
&#xD;
               -  Arrhythmias not controlled by medication&#xD;
&#xD;
               -  Unstable angina pectoris&#xD;
&#xD;
               -  Uncontrolled or symptomatic congestive heart failure (NYHA class III and IV)&#xD;
                  3.2.3 Uncontrolled or severe coagulopathies or a history of clinically&#xD;
                  significant bleeding within the past 6 months, including any of the following,&#xD;
                  but not limited to:&#xD;
&#xD;
               -  Epistaxis&#xD;
&#xD;
               -  Hemoptysis&#xD;
&#xD;
               -  Hematochezia&#xD;
&#xD;
               -  Hematuria&#xD;
&#xD;
               -  Gastrointestinal bleeding&#xD;
&#xD;
               -  Spontaneous or tumor related intracranial hemorrhage&#xD;
&#xD;
          -  Known predisposition for bleeding such as von Willebrand's disease or other such&#xD;
             condition(s)&#xD;
&#xD;
          -  Uncontrolled concurrent illness that would limit compliance with study requirements,&#xD;
             including any of the following, but limited to:&#xD;
&#xD;
               -  Uncontrolled infection.&#xD;
&#xD;
               -  Psychiatric illness/social situations&#xD;
&#xD;
          -  Prior malignancy except for non melanoma skin cancer and carcinoma in situ (of the&#xD;
             cervix or bladder), unless diagnosed and definitively treated more than 3 years prior&#xD;
             to 1st dose of investigational drug&#xD;
&#xD;
          -  Receiving any of the following medications:&#xD;
&#xD;
               -  Therapeutic doses of any anticoagulant, including low molecular weight heparin&#xD;
                  (LMWH). Concomitant use of warfarin, even at prophylactic doses, is prohibited&#xD;
&#xD;
               -  Digoxin, digitoxin, lanatoside C, or any type of digitalis alkaloids.&#xD;
&#xD;
               -  Colony stimulating factors (CSFs) that cannot be held during the monitoring&#xD;
                  period for dose limiting toxicities (DLT)&#xD;
&#xD;
          -  Has significant toxicities from prior treatment that have not resolved or stabilized&#xD;
&#xD;
          -  Known allergy to Coenzyme Q10&#xD;
&#xD;
          -  Known allergy or adverse reaction to oral, subcutaneous, or intravenous vitamin K&#xD;
&#xD;
          -  Is pregnant or lactating&#xD;
&#xD;
          -  Known to be positive for the human immunodeficiency virus (HIV). Note: HIV testing is&#xD;
             not required for eligibility, but if performed previously and was positive, the&#xD;
             subject is 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>Seema Nagpal</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford University, School of Medicine</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>January 5, 2017</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 13, 2017</study_first_posted>
  <last_update_submitted>August 9, 2021</last_update_submitted>
  <last_update_submitted_qc>August 9, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 10, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Seema Nagpal</investigator_full_name>
    <investigator_title>Clinical Assistant Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioblastoma</mesh_term>
    <mesh_term>Astrocytoma</mesh_term>
    <mesh_term>Gliosarcoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ubiquinone</mesh_term>
    <mesh_term>Coenzyme Q10</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 6, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/02/NCT03020602/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03020602
org study id: IRB-38514
secondary id: NCI-2016-01973
secondary id: BRN0035
nct id: NCT03020602
lead sponsor: 
has dmc: Yes
This phase I trial studies the side effects and best dose of ubidecarenone injectable
      nanosuspension (BPM31510) in treating patients with high-grade glioma (anaplastic astrocytoma
      or glioblastoma) that has come back and have been previously treated with bevacizumab.
      BPM31510 may stop the growth of tumor cells by blocking some of the enzymes needed for cell
      growth.
Primary Objective:

        -  Assess the safety and tolerability of BPM31510 plus vitamin K in subjects with
           high-grade glioma(HGG), defined as anaplastic astrocytoma (AA) or glioblastoma (GB) that
           has recurred on a BEV containing regimen.

      Secondary Objectives:

        -  To evaluate plasma pharmacokinetics (PK) when BPM31510 plus vitamin K is given to
           subjects with HGG recurrent on a BEV containing regimen.

      Exploratory Objectives:

        -  Estimate the overall survival in subjects with HGG recurrent on a BEV containing regimen
           from the 1st day of infusion of BPM31510 plus vitamin K to death.

        -  To evaluate the effects of BPM31510 plus vitamin K on shifting HGG metabolism to aerobic
           respiration by PET imaging.

        -  To evaluate the effects of BPM1510 plus vitamin K on MRI imaging by Response Assessment
           in Neuro Oncology (RANO) criteria [specifically progression free survival (PFS) and
           response rate (RR)].

        -  To evaluate plasma pharmacodynamics (PD) when BPM31510 plus vitamin K is given to
           subjects with HGG recurrent on a BEV containing regimen.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of patients with dose-limiting toxicities defined as thrombocytopenia >= grade 3, hemorrhage >= grade 3, and INR elevation >= grade 2 assessed by CTCAE v4.03
time frame: Up to 28 days
description: Will be tabulated at each dose, along with the result of the pooled adjacent violators algorithm as implemented in the Modified Toxicity Probability Interval (equal weights, and the weighted mean solver).
measure: Incidence of adverse events graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) version (v)4.03
time frame: Up to 30 days after last dose of BPM3150
description: Will be tabulated separately for each dose cohort, by Medical Dictionary for Regulatory Activities (MedDRA) major organ system and severity.
measure: Brain tumor metabolism as measured by PET
time frame: Up to 8 weeks
description: Standardized uptake value (SUV) of the HGG will be measured. SUV is the standard PET measure.
measure: Overall survival (OS)
time frame: From the date of BPM31510 initiation to death, assessed for up to 3 years
description: Kaplan-Meier survival estimates for OS will be presented for data at the maximum tolerated dose, with a 95% confidence interval using Greenwood's formula at 3.5 months and 7 months.
measure: PFS assessed by RANO criteria
time frame: Up to 3 years
measure: Response rate assessed by RANO criteria
time frame: Up to 3 years
arm group label: Treatment (BPM31510)
arm group type: Experimental
description: Patients receive ubidecarenone injectable nanosuspension IV over 72 hours twice weekly. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (BPM31510)
intervention type: Other
intervention name: Pharmacological Study
description: Correlative studies
arm group label: Treatment (BPM31510)
intervention type: Drug
intervention name: Ubidecarenone Injectable Nanosuspension
description: Given IV
arm group label: Treatment (BPM31510)
other name: BP31510
other name: Coenzyme Q10 Injectable Nanosuspension
other name: Ubiquinone Injectable Nanosuspension
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Seema Nagpal
role: Principal Investigator
affiliation: Stanford University
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Stanford University
investigator full name: Seema Nagpal
investigator title: Clinical Assistant Professor
mesh term: Glioblastoma
mesh term: Astrocytoma
mesh term: Gliosarcoma
mesh term: Ubiquinone
mesh term: Coenzyme Q10
sharing ipd: No
provided document: 