<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/NCT03808870</url>
  </required_header>
  <id_info>
    <org_study_id>NBM-BMX-002</org_study_id>
    <nct_id>NCT03808870</nct_id>
  </id_info>
  <brief_title>A Safety and Pharmacokinetic Study of NBM-BMX Administered Orally to Asian Patients With Advanced Cancer</brief_title>
  <official_title>A Phase 1, Open-label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Efficacy of NBM-BMX in Asian Subjects With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NatureWise Biotech &amp; Medicals Corporation</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>NatureWise Biotech &amp; Medicals Corporation</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      NBM-BMX is an orally available new chemical entity to inhibit HDAC8 activity specifically,&#xD;
      being developed as a potential anti-cancer therapeutic by NatureWise. The objectives of this&#xD;
      study are to evaluate the safety, pharmacokinetics, and preliminary efficacy of NBM-BMX as&#xD;
      monotherapy in subjects with advanced solid tumors (Arm A) or in combination with the&#xD;
      standard of care treatment (i.e., concomitant RT/TMZ followed by adjuvant TMZ) in subjects&#xD;
      with newly diagnosed glioblastoma (Arm B).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 28, 2018</start_date>
  <completion_date type="Actual">February 16, 2022</completion_date>
  <primary_completion_date type="Actual">February 12, 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>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose limiting toxicity (DLT) of NBM-BMX [Safety and Tolerability]</measure>
    <time_frame>up to 28 days</time_frame>
    <description>Toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum tolerated dose (MTD) of NBM-BMX [Safety and Tolerability]</measure>
    <time_frame>up to 28 days</time_frame>
    <description>The MTD will be defined as the dose level at which at most one of six patients experiences a DLT after 28 days of treatment have occurred, with the next higher dose having at least 2/3 or 2/6 patients experiencing a DLT.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Preliminary assessment of anti-tumor activity by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) [Efficacy]</measure>
    <time_frame>at least 8 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-last) of NBM-BMX [Pharmacokinetics]</measure>
    <time_frame>Day 1, 8 and 15 for Cycle 1 only (each cycle is 28 days)</time_frame>
    <description>AUC(0-last): area under the plasma concentration versus time curve to the time of the last measurable concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of NBM-BMX [Pharmacokinetics]</measure>
    <time_frame>Day 1, 8 and 15 for Cycle 1 only (each cycle is 28 days)</time_frame>
    <description>Cmax: maximum plasma concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax of NBM-BMX [Pharmacokinetics]</measure>
    <time_frame>Day 1, 8 and 15 for Cycle 1 only (each cycle is 28 days)</time_frame>
    <description>Tmax: time to maximum plasma concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T(1/2) of NBM-BMX [Pharmacokinetics]</measure>
    <time_frame>Day 1, 8 and 15 for Cycle 1 only (each cycle is 28 days)</time_frame>
    <description>T(1/2): terminal elimination half-life</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Malignant Neoplasm</condition>
  <arm_group>
    <arm_group_label>NBM-BMX</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NBM-BMX softgel capsules</intervention_name>
    <description>Patients will initially receive NBM-BMX orally once a day at 100 mg per day.</description>
    <arm_group_label>NBM-BMX</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically or cytologically confirmed advanced, non-resectable, and/or metastatic&#xD;
             solid tumor refractory to standard of care therapy, or for whom no standard of care&#xD;
             therapy is available, or who were not amenable to established forms of treatment.&#xD;
&#xD;
          2. Solid tumors must have measurable or evaluable disease as per Response Evaluation&#xD;
             Criteria in Solid Tumors (RECIST) 1.1.&#xD;
&#xD;
          3. Female or male at 20 years of age or older.&#xD;
&#xD;
          4. ECOG performance status 0 to 2.&#xD;
&#xD;
          5. Recovered from prior treatment-related toxicity to at least grade 1 with exception of&#xD;
             grade 2 alopecia.&#xD;
&#xD;
          6. Adequate organ function as defined by the following criteria:&#xD;
&#xD;
               -  Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤3 x&#xD;
                  upper limit of normal (ULN), or AST and ALT ≤5 x ULN if liver function&#xD;
                  abnormalities are due to underlying malignancy&#xD;
&#xD;
               -  Total serum bilirubin ≤1.5 x ULN (except for subjects with documented Gilbert's&#xD;
                  syndrome)&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1500/µL&#xD;
&#xD;
               -  Platelets ≥ 90,000/µL&#xD;
&#xD;
               -  Hemoglobin ≥ 9.0 g/dL&#xD;
&#xD;
               -  Serum creatinine ≤ 2.0 x ULN&#xD;
&#xD;
          7. Signed and dated informed consent document indicating that the subject (or legally&#xD;
             acceptable representative) has been informed of all the pertinent aspects of the trial&#xD;
             prior to enrollment.&#xD;
&#xD;
          8. Willingness and ability to comply with scheduled visits, treatment plans, laboratory&#xD;
             tests, and other study procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects presenting with any of the following will not be included in the trial:&#xD;
&#xD;
          1. Major surgery or radiation therapy within 28 days of starting study treatment.&#xD;
&#xD;
          2. Systemic anti-cancer therapy within 28 days or 5 half-lives (whichever is shorter) of&#xD;
             starting study treatment.&#xD;
&#xD;
          3. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.&#xD;
&#xD;
          4. Current treatment on another clinical trial.&#xD;
&#xD;
          5. Spinal cord compression, carcinomatous meningitis, or leptomeningeal disease unless&#xD;
             appropriately treated and neurologically stable for at least 4 weeks.&#xD;
&#xD;
          6. Any of the following within the 12 months prior to starting study treatment:&#xD;
             myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass&#xD;
             graft, congestive heart failure, or cerebrovascular accident including transient&#xD;
             ischemic attack; within 6 months prior to starting study treatment for pulmonary&#xD;
             embolus. However, upon agreement between the investigator and medical monitor, the&#xD;
             6-month post-event-free period for a subject with a pulmonary embolus can be waived if&#xD;
             due to advanced cancer. Appropriate treatment with anticoagulants is permitted.&#xD;
&#xD;
          7. NYHA Class III or IV heart failure and known history of QTc prolongation or Torsade de&#xD;
             Pointes.&#xD;
&#xD;
          8. Use of medications known to significantly prolong the QTc interval (e.g.,&#xD;
             anti-arrhythmic and psychotropic medications).&#xD;
&#xD;
          9. Hypertension that cannot be controlled by medications.&#xD;
&#xD;
         10. Current treatment with therapeutic doses of warfarin (low dose warfarin up to 2 mg PO&#xD;
             daily for deep vein thrombosis prophylaxis is allowed).&#xD;
&#xD;
         11. Known human immunodeficiency virus (HIV)-positive and is receiving anti-retroviral&#xD;
             therapy.&#xD;
&#xD;
         12. Positive test for hepatitis B (HBsAg) or hepatitis C (anti-HCV antibody).&#xD;
&#xD;
         13. History of receiving organ transplantation or immune disorders that require continuous&#xD;
             immunosuppressant agent therapy.&#xD;
&#xD;
         14. Pregnancy or breastfeeding. Female subjects must be surgically sterile or be&#xD;
             postmenopausal, or must agree to the use of effective contraception during the period&#xD;
             of therapy. All female subjects with reproductive potential must have a negative&#xD;
             pregnancy test (serum or urine) prior to enrollment. Male subjects must be surgically&#xD;
             sterile or must agree to use effective contraception during the period of therapy. The&#xD;
             definition of effective contraception will be based on the judgment of the principal&#xD;
             investigator or a designated associate.&#xD;
&#xD;
         15. Other severe acute or chronic medical or psychiatric conditions or laboratory&#xD;
             abnormalities that would impart, in the judgment of the investigator and/or medical&#xD;
             monitor, excess risk associated with study participation or study drug administration,&#xD;
             which would make the subject inappropriate for entry into this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>National Cheng Kung University Hospital</name>
      <address>
        <city>Tainan</city>
        <zip>704</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Veterans General Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>112</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>January 10, 2019</study_first_submitted>
  <study_first_submitted_qc>January 16, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>August 11, 2023</last_update_submitted>
  <last_update_submitted_qc>August 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 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>Neoplasms</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03808870
org study id: NBM-BMX-002
nct id: NCT03808870
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
NBM-BMX is an orally available new chemical entity to inhibit HDAC8 activity specifically,
      being developed as a potential anti-cancer therapeutic by NatureWise. The objectives of this
      study are to evaluate the safety, pharmacokinetics, and preliminary efficacy of NBM-BMX as
      monotherapy in subjects with advanced solid tumors (Arm A) or in combination with the
      standard of care treatment (i.e., concomitant RT/TMZ followed by adjuvant TMZ) in subjects
      with newly diagnosed glioblastoma (Arm B).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose limiting toxicity (DLT) of NBM-BMX [Safety and Tolerability]
time frame: up to 28 days
description: Toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0
measure: Maximum tolerated dose (MTD) of NBM-BMX [Safety and Tolerability]
time frame: up to 28 days
description: The MTD will be defined as the dose level at which at most one of six patients experiences a DLT after 28 days of treatment have occurred, with the next higher dose having at least 2/3 or 2/6 patients experiencing a DLT.
measure: Preliminary assessment of anti-tumor activity by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) [Efficacy]
time frame: at least 8 weeks
measure: AUC(0-last) of NBM-BMX [Pharmacokinetics]
time frame: Day 1, 8 and 15 for Cycle 1 only (each cycle is 28 days)
description: AUC(0-last): area under the plasma concentration versus time curve to the time of the last measurable concentration
measure: Cmax of NBM-BMX [Pharmacokinetics]
time frame: Day 1, 8 and 15 for Cycle 1 only (each cycle is 28 days)
description: Cmax: maximum plasma concentration
measure: Tmax of NBM-BMX [Pharmacokinetics]
time frame: Day 1, 8 and 15 for Cycle 1 only (each cycle is 28 days)
description: Tmax: time to maximum plasma concentration
measure: T(1/2) of NBM-BMX [Pharmacokinetics]
time frame: Day 1, 8 and 15 for Cycle 1 only (each cycle is 28 days)
description: T(1/2): terminal elimination half-life
arm group label: NBM-BMX
arm group type: Experimental
intervention type: Drug
intervention name: NBM-BMX softgel capsules
description: Patients will initially receive NBM-BMX orally once a day at 100 mg per day.
arm group label: NBM-BMX
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Neoplasms