<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/NCT03256331</url>
  </required_header>
  <id_info>
    <org_study_id>BELXHG-SP001</org_study_id>
    <nct_id>NCT03256331</nct_id>
  </id_info>
  <brief_title>Evaluate the Safety of BEL-X-HG in Advanced Cancer Patients</brief_title>
  <official_title>A Phase I, Open-Label, Dose Escalation and Extension Study to Evaluate the Safety, Tolerability and Preliminary Effects of Oral BEL-X-HG in Patients With Advanced Refractory Solid Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Belx Bio-Pharmaceutical (Taiwan) Corporation</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>A2 Healthcare Taiwan Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Belx Bio-Pharmaceutical (Taiwan) Corporation</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 is a Phase I, open-label, uncontrolled, multicenter dose escalation and extension study&#xD;
      to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), to evaluate&#xD;
      safety / tolerability and preliminary effects of BEL-X-HG in patients with advanced&#xD;
      refractory solid tumors. Dose escalation during the study will be made based on dose-limiting&#xD;
      toxicity (DLT).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will be carried out in 2 parts:&#xD;
&#xD;
      Part 1: A sequential Dose Escalation Part of four doses following a 3 + 3 design where dose&#xD;
      escalation will be made based on dose-limiting toxicity (DLT), for a single cycle (28-days)&#xD;
      of BEL-X-HG treatment&#xD;
&#xD;
      Part 2: A Dose Extension Part of up to 5 cycles (28-days each) at the same dose level&#xD;
      (starting dose) of BEL-X-HG treatment&#xD;
&#xD;
      Approximately 24-48 eligible subjects with confirmed advanced refractory solid tumors will be&#xD;
      enrolled sequentially, in 3 subject cohorts, from the lower to the higher dose cohort into&#xD;
      the study. Escalating dose levels of BEL-X-HG in 4 study cohorts and one modified dose will&#xD;
      be as follows:&#xD;
&#xD;
      Cohort 1: Dose level 1 - 0.5 g/day (0.25 g, bid)&#xD;
&#xD;
      Cohort 2: Dose level 2 - 1.0 g/day (0.5 g, bid)&#xD;
&#xD;
      Cohort 3: Dose level 3 - 2.0 g/day (1.0 g, bid)&#xD;
&#xD;
      Cohort 4: Dose level 4 - 4.0 g/day (2.0 g, bid)&#xD;
&#xD;
      Modified dose level Cohort 5: Dose level 5 - 1.5 g/day (0.75g bid) This re-escalation is&#xD;
      allowed only when dose de-escalates from Dose level 3 to Dose level 2, and 1 DLT in 6&#xD;
      evaluable subjects of Dose level 2.&#xD;
&#xD;
      BEL-X-HG will be administered orally at the assigned dose level for a single cycle consisting&#xD;
      of 28 days during the Dose Escalation Part to each subject. Thereafter, if eligible and&#xD;
      willing, subjects can continue to Extension Part for 5 more cycles of treatment (each cycle&#xD;
      lasting 28 days), at the same assigned dose level of BEL-X-HG treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    In the light of the on-going COVID-19 pandemic and the resulted difficulty in patient&#xD;
    recruitment.&#xD;
  </why_stopped>
  <start_date type="Actual">June 21, 2017</start_date>
  <completion_date type="Actual">March 30, 2020</completion_date>
  <primary_completion_date type="Actual">March 30, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>A sequential Dose Escalation Part of four doses following a 3 + 3 design.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Tolerated Dose (MTD)</measure>
    <time_frame>28 days (first treatment cycle of every subjects)</time_frame>
    <description>The prior dose level below the dose level at which ≥2/3 or ≥2/6 subjects suffer dose-limiting toxicity (DLT).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events</measure>
    <time_frame>up to 168 days (up to 6 cycles of each enrolled subjects)</time_frame>
    <description>Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor response per Response Evaluation Criteria in Solid Tumors (RECIST)</measure>
    <time_frame>up to 168 days (up to 6 cycles of each enrolled subjects)</time_frame>
    <description>Tumor response per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxidative stress</measure>
    <time_frame>up to 168 days (up to 6 cycles of each enrolled subjects)</time_frame>
    <description>Oxidative stress</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>nutritional status</measure>
    <time_frame>up to 168 days (up to 6 cycles of each enrolled subjects)</time_frame>
    <description>serum prealbumin, triglyceride, and total cholesterol</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>immunological status</measure>
    <time_frame>up to 168 days (up to 6 cycles of each enrolled subjects)</time_frame>
    <description>TNF-alpha, IL-1, IL-2, IL-4, and IL-6</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cachexia status</measure>
    <time_frame>up to 168 days (up to 6 cycles of each enrolled subjects)</time_frame>
    <description>fast blood glucose, C-reactive protein, and testosteron</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life (QoL) of patients with advanced refractory solid tumors</measure>
    <time_frame>up to 168 days (up to 6 cycles of each enrolled subjects)</time_frame>
    <description>SF-36 Quality of Life (QoL) Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>liver function</measure>
    <time_frame>up to 168 days (up to 6 cycles of each enrolled subjects)</time_frame>
    <description>serum AST, ALT, AKP, albumin, gamma-GT, ferritin, PT/INR and APRI</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>Advanced Solid Tumors</condition>
  <arm_group>
    <arm_group_label>BEL-X-HG</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3+3 dose escalation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BEL-X-HG</intervention_name>
    <description>This study will be carried out in 2 parts:&#xD;
A sequential Dose Escalation Part of four doses following a 3 + 3 design where dose escalation will be made based on DLT, for a single cycle (28 days) of BEL-X-HG treatment&#xD;
A Dose Extension Part of up to 5 cycles (28 days each) at the same dose level (starting dose) of BEL-X-HG treatment&#xD;
Escalating dose levels of BEL-X-HG in 5 study cohorts and one modified dose will be as follows:&#xD;
Cohort 1: Dose level 1 - 0.5 g/day (0.25 g, bid)&#xD;
Cohort 2: Dose level 2 - 1.0 g/day (0.5 g, bid)&#xD;
Cohort 3: Dose level 3 - 2.0 g/day (1.0 g, bid)&#xD;
Cohort 4: Dose level 4 - 4.0 g/day (2.0 g, bid) Modified dose level Cohort 5: Dose level 5 - 1.5 g/day (0.75g bid) This re-escalation is allowed only when dose de-escalates from Dose level 3 to Dose level 2, and 1 DLT in 6 evaluable subjects of Dose level 2.</description>
    <arm_group_label>BEL-X-HG</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female patients of age ≥20 years&#xD;
&#xD;
          2. Pathologically or cytologically confirmed advanced refractory solid tumors for which&#xD;
             standard therapy proven to provide clinical benefit does not exist or is no longer&#xD;
             effective. It is acceptable for HCC subjects with Child Pugh stage A to confirm&#xD;
             diagnosis of the advanced refractory solid tumors by imaging (CT scan).&#xD;
&#xD;
          3. Evaluable disease, at least one measurable target lesion on imaging by RECIST 1.1&#xD;
             (Response Evaluation Criteria in Solid Tumors) criteria.&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2&#xD;
&#xD;
          5. Life expectancy ≥ 3 months&#xD;
&#xD;
          6. Patients able to swallow and retain orally administered medication and does not have&#xD;
             any clinically significant gastrointestinal abnormalities that may alter absorption&#xD;
             such as malabsorption syndrome or major restriction of the stomach or bowels&#xD;
&#xD;
          7. Laboratory values at screening and baseline (Day 1) of:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1,500 /mm3&#xD;
&#xD;
               -  Platelets ≥ 75,000 /mm3&#xD;
&#xD;
               -  Hemoglobin (Hb) ≥ 8.5 g/dL&#xD;
&#xD;
               -  Serum creatinine (Cr.) ≤1.5 mg/dL or estimated Glomerular Filtration Rate (eGFR)&#xD;
                  ≥ 60 mL/min/1.73 m2.&#xD;
&#xD;
             MDRD Study equation: eGFR = 186 x (SCr)^-1.154 x (age)^0.203 x (0.742 if female) x&#xD;
             (1.210 if African American) SCr: serum creatinine in mg/dL; age: in year&#xD;
&#xD;
          8. Patients with primary liver cancer or hepatic metastasis are eligible to enroll,&#xD;
             provided that, at screening and baseline (Day 1), the following criteria are met:&#xD;
&#xD;
               -  Total bilirubin (T-Bil) ≤2.0 mg/dL&#xD;
&#xD;
               -  AST and ALT ≤ 5 times the institutional upper limit of normal&#xD;
&#xD;
               -  Child-Pugh Class A; (Score ≤6)&#xD;
&#xD;
               -  Serum albumin ≥2.8 g/dL&#xD;
&#xD;
          9. Patients with a history of esophageal bleeding have varices that have been sclerosed&#xD;
             or banded and no bleeding episodes have occurred during the prior 6 months&#xD;
&#xD;
         10. If history of brain metastases treated with radiation therapy, radiation therapy is&#xD;
             required to be completed at least 3 months prior to enrolment and metastasis achieve&#xD;
             stable disease (SD) since radiation completion&#xD;
&#xD;
         11. Must have recovered from toxicities of previous anti-cancer treatments to NCI-CTCAE&#xD;
             version 4.03 grade 1 or lower, except for alopecia&#xD;
&#xD;
         12. Females patient must be either of non-childbearing potential, i.e. surgically&#xD;
             sterilized (e.g. tubal ligation, hysterectomy, or ovariectomy) or one year post-&#xD;
             menopausal; or, if of childbearing potential, confirmed not pregnant at screening and&#xD;
             use of two adequate contraceptive precautions (as per investigator) i.e. condoms plus&#xD;
             oral contraceptives or condoms plus endometrial contraceptive devices, during the&#xD;
             entire treatment period of this study and for 6 months after exiting from the study&#xD;
&#xD;
         13. Male patients with female partners of childbearing potential must be willing to use a&#xD;
             reliable form of contraception (condoms), from screening until 6 months after existing&#xD;
             from the study&#xD;
&#xD;
         14. Given signed and dated written informed consent and willing/able to comply with all&#xD;
             protocol required visits/procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Primary major surgery &lt; 4 weeks prior to the planned first study treatment day&#xD;
&#xD;
          2. Lactating or pregnant women or plans to be become pregnant&#xD;
&#xD;
          3. Except for alopecia, any drug-related AE from any previous treatments not recovered to&#xD;
             NCI-CTCAE version 4.03 grade 1 or lower prior to the planned first study treatment day&#xD;
&#xD;
          4. With active systemic infections, active and clinically significant cardiac diseases,&#xD;
             active gastrointestinal diseases, active pulmonary diseases, or medical conditions&#xD;
             that may significantly affect adequate absorption of investigational product.&#xD;
&#xD;
          5. Known allergy to BEL-X-HG or its formulation excipients&#xD;
&#xD;
          6. History of autoimmune disease that in the investigator's opinion may be significant to&#xD;
             exclude participation in the study&#xD;
&#xD;
          7. Use of any investigational agents or non-registered product within 4 weeks of baseline&#xD;
&#xD;
          8. Known human immunodeficiency virus (HIV) positivity&#xD;
&#xD;
          9. Known hepatitis B virus (HBV) or hepatitis C virus (HCV) carrier who has:&#xD;
&#xD;
               -  serum HBV DNA &gt; 2,000 IU/mL and abnormal ALT (&gt; 5 ULN) (for HBV carrier)&#xD;
&#xD;
               -  abnormal ALT (&gt; 5 ULN) (for HCV carrier)&#xD;
&#xD;
         10. With conditions, judged by the investigator, as unsuitable for the study&#xD;
&#xD;
         11. Mean QTc with Fridericia's correction (QTcF*) greater than 450 ms in screening ECG or&#xD;
             history of familial long QT syndrome&#xD;
&#xD;
             *: Fridericia's formula:&#xD;
&#xD;
         12. Any cancer-directed therapy (chemotherapy, radiotherapy, biological or immunotherapy,&#xD;
             etc.) within 4 weeks or 5 half-lives, (whichever is shorter) of baseline&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chia-Chi Lin, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Taiwan University Hospital</affiliation>
  </overall_official>
  <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>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>August 13, 2017</study_first_submitted>
  <study_first_submitted_qc>August 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <last_update_submitted>May 29, 2020</last_update_submitted>
  <last_update_submitted_qc>May 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 1, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03256331
org study id: BELXHG-SP001
nct id: NCT03256331
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase I, open-label, uncontrolled, multicenter dose escalation and extension study
      to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), to evaluate
      safety / tolerability and preliminary effects of BEL-X-HG in patients with advanced
      refractory solid tumors. Dose escalation during the study will be made based on dose-limiting
      toxicity (DLT).
This study will be carried out in 2 parts:

      Part 1: A sequential Dose Escalation Part of four doses following a 3 + 3 design where dose
      escalation will be made based on dose-limiting toxicity (DLT), for a single cycle (28-days)
      of BEL-X-HG treatment

      Part 2: A Dose Extension Part of up to 5 cycles (28-days each) at the same dose level
      (starting dose) of BEL-X-HG treatment

      Approximately 24-48 eligible subjects with confirmed advanced refractory solid tumors will be
      enrolled sequentially, in 3 subject cohorts, from the lower to the higher dose cohort into
      the study. Escalating dose levels of BEL-X-HG in 4 study cohorts and one modified dose will
      be as follows:

      Cohort 1: Dose level 1 - 0.5 g/day (0.25 g, bid)

      Cohort 2: Dose level 2 - 1.0 g/day (0.5 g, bid)

      Cohort 3: Dose level 3 - 2.0 g/day (1.0 g, bid)

      Cohort 4: Dose level 4 - 4.0 g/day (2.0 g, bid)

      Modified dose level Cohort 5: Dose level 5 - 1.5 g/day (0.75g bid) This re-escalation is
      allowed only when dose de-escalates from Dose level 3 to Dose level 2, and 1 DLT in 6
      evaluable subjects of Dose level 2.

      BEL-X-HG will be administered orally at the assigned dose level for a single cycle consisting
      of 28 days during the Dose Escalation Part to each subject. Thereafter, if eligible and
      willing, subjects can continue to Extension Part for 5 more cycles of treatment (each cycle
      lasting 28 days), at the same assigned dose level of BEL-X-HG treatment.
intervention model: Sequential Assignment
intervention model description: A sequential Dose Escalation Part of four doses following a 3 + 3 design.
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD)
time frame: 28 days (first treatment cycle of every subjects)
description: The prior dose level below the dose level at which ≥2/3 or ≥2/6 subjects suffer dose-limiting toxicity (DLT).
measure: Incidence of Treatment-Emergent Adverse Events
time frame: up to 168 days (up to 6 cycles of each enrolled subjects)
description: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
measure: Tumor response per Response Evaluation Criteria in Solid Tumors (RECIST)
time frame: up to 168 days (up to 6 cycles of each enrolled subjects)
description: Tumor response per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
measure: Oxidative stress
time frame: up to 168 days (up to 6 cycles of each enrolled subjects)
description: Oxidative stress
measure: nutritional status
time frame: up to 168 days (up to 6 cycles of each enrolled subjects)
description: serum prealbumin, triglyceride, and total cholesterol
measure: immunological status
time frame: up to 168 days (up to 6 cycles of each enrolled subjects)
description: TNF-alpha, IL-1, IL-2, IL-4, and IL-6
measure: cachexia status
time frame: up to 168 days (up to 6 cycles of each enrolled subjects)
description: fast blood glucose, C-reactive protein, and testosteron
measure: Quality of life (QoL) of patients with advanced refractory solid tumors
time frame: up to 168 days (up to 6 cycles of each enrolled subjects)
description: SF-36 Quality of Life (QoL) Questionnaire
measure: liver function
time frame: up to 168 days (up to 6 cycles of each enrolled subjects)
description: serum AST, ALT, AKP, albumin, gamma-GT, ferritin, PT/INR and APRI
arm group label: BEL-X-HG
arm group type: Experimental
description: 3+3 dose escalation
intervention type: Drug
intervention name: BEL-X-HG
description: This study will be carried out in 2 parts:
A sequential Dose Escalation Part of four doses following a 3 + 3 design where dose escalation will be made based on DLT, for a single cycle (28 days) of BEL-X-HG treatment
A Dose Extension Part of up to 5 cycles (28 days each) at the same dose level (starting dose) of BEL-X-HG treatment
Escalating dose levels of BEL-X-HG in 5 study cohorts and one modified dose will be as follows:
Cohort 1: Dose level 1 - 0.5 g/day (0.25 g, bid)
Cohort 2: Dose level 2 - 1.0 g/day (0.5 g, bid)
Cohort 3: Dose level 3 - 2.0 g/day (1.0 g, bid)
Cohort 4: Dose level 4 - 4.0 g/day (2.0 g, bid) Modified dose level Cohort 5: Dose level 5 - 1.5 g/day (0.75g bid) This re-escalation is allowed only when dose de-escalates from Dose level 3 to Dose level 2, and 1 DLT in 6 evaluable subjects of Dose level 2.
arm group label: BEL-X-HG
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Chia-Chi Lin, MD, PhD
role: Principal Investigator
affiliation: National Taiwan University Hospital
facility: 
facility: 
country: Taiwan
responsible party type: Sponsor
sharing ipd: No