xml: <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/NCT06034977</url>
    </required_header>
    <id_info>
      <org_study_id>POLARIS 2023-LY-1</org_study_id>
      <nct_id>NCT06034977</nct_id>
    </id_info>
    <brief_title>Phase 2 Study of ADI-PEG 20 Plus Lenvatinib Treatment in Subjects With Unresectable Hepatocellular Carcinoma</brief_title>
    <official_title>Genotype Selected, Randomized, Open Label, Phase 2 Study of ADI-PEG 20 Plus Lenvatinib Treatment in Subjects With Unresectable Hepatocellular Carcinoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Chang Gung Memorial Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Chang Gung Memorial Hospital</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        To compare the clinical outcomes of Lenvatinib treatment alone or Lenvatinib + ADI-PEG20&#xD;
        combination treatment in advanced HCC patients with BCLC stage C.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">December 1, 2023</start_date>
    <completion_date type="Anticipated">July 23, 2026</completion_date>
    <primary_completion_date type="Anticipated">July 23, 2026</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>Overall survival</measure>
      <time_frame>2 years after the last enrollment</time_frame>
      <description>Overall survival after the start of the intervention</description>
    </primary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">120</enrollment>
    <condition>Hepatocellular Carcinoma</condition>
    <arm_group>
      <arm_group_label>Lenvatinib</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Advanced HCC patients treated by Lenvatinib.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Lenvatinib + ADI-PEG20</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Advanced HCC patients treated by Lenvatinib + ADI-PEG20.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>ADI-PEG20</intervention_name>
      <description>Lenvatinib + ADI-PEG20 combination treatment.</description>
      <arm_group_label>Lenvatinib</arm_group_label>
      <arm_group_label>Lenvatinib + ADI-PEG20</arm_group_label>
      <other_name>pegylated arginine deiminase</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Prior diagnosis of HCC confirmed by radiology, histology, or cytology.&#xD;
  &#xD;
            2. Patients were rs-6025211 non-TT with rs9679162 non-GG genotype , or serum arginine&#xD;
               level ≥ 84.2 µM with rs9679162 non-GG genotype. Treatment naïve or under Lenvatinib&#xD;
               treatment for &lt; 2 months.&#xD;
  &#xD;
            3. Measurable disease using RECIST 1.1 (Appendix A). At least 1 measurable lesion must be&#xD;
               present.&#xD;
  &#xD;
            4. Child-Pugh (cirrhosis status) score class A (Appendix C).&#xD;
  &#xD;
            5. Barcelona Cancer of the Liver (BCLC) stage C (Appendix B).&#xD;
  &#xD;
            6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment&#xD;
               (Appendix D).&#xD;
  &#xD;
            7. Expected survival of at least 3 months.&#xD;
  &#xD;
            8. Age &gt;18 years.&#xD;
  &#xD;
            9. Fully recovered from prior surgery and none within 2 weeks prior to week 1 visit.&#xD;
               Liver biopsy for HCC confirmation is allowed.&#xD;
  &#xD;
           10. Female subjects and male subjects must be asked to use appropriate contraception for&#xD;
               both the male and female for the duration of the study. Male partners of female&#xD;
               subjects and female partners of male subjects must agree to use two forms of&#xD;
               contraception or agree to refrain from intercourse for the duration of the study if&#xD;
               they are of childbearing potential. Females of childbearing potential must not be&#xD;
               pregnant at the start of the study, and a serum human chorionic gonadotropin (HCG)&#xD;
               pregnancy test must be negative before entry into the study. If positive HCG pregnancy&#xD;
               test, further evaluation to rule out pregnancy must be performed according to GCP&#xD;
               before this subject is deemed eligible. Females not of childbearing potential must be&#xD;
               post-menopausal (defined as cessation of regular menstrual period for at least 12&#xD;
               months).&#xD;
  &#xD;
           11. Informed consent must be obtained prior to study initiation.&#xD;
  &#xD;
           12. No concurrent investigational studies are allowed.&#xD;
  &#xD;
           13. Total bilirubin &lt; 2.5 mg/dL and no evidence of bile obstruction.&#xD;
  &#xD;
           14. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 x upper&#xD;
               limit of normal range.&#xD;
  &#xD;
           15. Serum albumin level ≥ 3.0 g/dl.&#xD;
  &#xD;
           16. Prothrombin time (PT)-international normalized ratio (INR): PT &lt;3 seconds above&#xD;
               control or INR &lt;1.7.&#xD;
  &#xD;
           17. Absolute neutrophil count (ANC) &gt;1,500/µL.&#xD;
  &#xD;
           18. Platelets &gt;50,000/µL.&#xD;
  &#xD;
           19. Serum uric acid ≤ 8 mg/dL (with or without medication control).&#xD;
  &#xD;
           20. Serum creatinine ≤ 1.5 x the upper limit of normal range, or, if serum creatinine &gt;1.5&#xD;
               x the upper limit of normal range, then the creatinine clearance must be ≥ 40 mL/min.&#xD;
  &#xD;
           21. Subjects with active hepatitis B or C on anti-viremic compounds may remain on such&#xD;
               treatment, except for interferon.&#xD;
  &#xD;
           22. Encephalopathy - none or mild (grade 1 or 2, by Child-Pugh classification); lactulose&#xD;
               of other supportive care allowed.&#xD;
  &#xD;
           23. Ascites - absent or slight (by Child-Pugh classification); diuretic therapy allowed.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Candidate for potential curative therapies (i.e., resection or transplantation) or&#xD;
               eligible for approved systemic therapies according to the labeling of such drugs.&#xD;
  &#xD;
            2. Prior allograft transplantation including liver transplantation.&#xD;
  &#xD;
            3. Subjects who have not fully recovered from toxicities associated with previous HCC&#xD;
               loco-regional or systemic therapies, except for Grade 1 alopecia.&#xD;
  &#xD;
            4. Serious infection requiring treatment with systemically administered antibiotics at&#xD;
               the time of study entrance, or an infection requiring systemic antibiotic therapy&#xD;
               within 7 days prior to the first dose of study treatment.&#xD;
  &#xD;
            5. Pregnancy or lactation.&#xD;
  &#xD;
            6. Expected non-compliance.&#xD;
  &#xD;
            7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
               infection, symptomatic congestive heart failure (New York Heart Association Class III&#xD;
               or IV), cardiac arrhythmia, or psychiatric illness, social situations that would limit&#xD;
               compliance with study requirements.&#xD;
  &#xD;
            8. Subjects with history of another primary cancer, including co-existent second&#xD;
               malignancy, with the exception of: a) curatively resected non-melanoma skin cancer; b)&#xD;
               curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no&#xD;
               known active disease present or in the opinion of the investigator will not affect&#xD;
               patient outcome.&#xD;
  &#xD;
            9. Subjects who had been treated with ADI-PEG 20 previously.&#xD;
  &#xD;
           10. History of uncontrolled seizure disorder not related to underlying cancer.&#xD;
  &#xD;
           11. Known HIV positivity, or active hepatitis B infection, or active hepatitis C infection&#xD;
               (AST or ALT &gt; 5 x upper limit of normal).&#xD;
  &#xD;
           12. Allergy to pegylated compounds.&#xD;
  &#xD;
           13. Allergy to E. coli drug products (such as GMCSF).&#xD;
  &#xD;
           14. Bleeding esophageal or gastric varices within the prior three months, except if banded&#xD;
               or treated.&#xD;
  &#xD;
           15. Uncontrolled ascites (defined as not easily controlled with diuretic treatment).&#xD;
  &#xD;
           16. Having received any blood transfusion, blood component preparation, erythropoietin,&#xD;
               albumin preparation, or granulocyte colony stimulating factors (G-CSF) within 7 days&#xD;
               prior to screening laboratories or after screening laboratories have been obtained&#xD;
               until week 1 visit.&#xD;
  &#xD;
           17. Use of traditional medicines approved by local authorities, including but not limited&#xD;
               to Chinese herbs within 2 weeks prior to week 1 visit.&#xD;
  &#xD;
           18. Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2.&#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>Wei-Ting Chen, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Chang Gung Memorial Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Wei-Ting Chen, MD</last_name>
      <phone>886-3-3281200</phone>
      <phone_ext>8107</phone_ext>
      <email>weiting1972@gmail.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Taiwan Linkou Chang Gung Memorial Hospital</last_name>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Chang Gung Memorial Hospital, Linkou branch</name>
        <address>
          <city>Taoyuan</city>
          <zip>333</zip>
          <country>Taiwan</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Wei-Ting Chen, MD</last_name>
      </contact>
    </location>
    <location_countries>
      <country>Taiwan</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 6, 2023</study_first_submitted>
    <study_first_submitted_qc>September 6, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 6, 2023</last_update_submitted>
    <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Chang Gung Memorial Hospital</investigator_affiliation>
      <investigator_full_name>Wei-Ting Chen</investigator_full_name>
      <investigator_title>Director, Chang Gung Memorial Hospital</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carcinoma</mesh_term>
      <mesh_term>Carcinoma, Hepatocellular</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06034977
  org study id: POLARIS 2023-LY-1
  nct id: NCT06034977
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  To compare the clinical outcomes of Lenvatinib treatment alone or Lenvatinib + ADI-PEG20
        combination treatment in advanced HCC patients with BCLC stage C.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Overall survival
  time frame: 2 years after the last enrollment
  description: Overall survival after the start of the intervention
  arm group label: Lenvatinib
  arm group type: Placebo Comparator
  description: Advanced HCC patients treated by Lenvatinib.
  arm group label: Lenvatinib + ADI-PEG20
  arm group type: Experimental
  description: Advanced HCC patients treated by Lenvatinib + ADI-PEG20.
  intervention type: Drug
  intervention name: ADI-PEG20
  description: Lenvatinib + ADI-PEG20 combination treatment.
  arm group label: Lenvatinib
  arm group label: Lenvatinib + ADI-PEG20
  other name: pegylated arginine deiminase
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Wei-Ting Chen, MD
  role: Principal Investigator
  affiliation: Chang Gung Memorial Hospital
  last name: Wei-Ting Chen, MD
  phone: 886-3-3281200
  phone ext: 8107
  email: weiting1972@gmail.com
  last name: Taiwan Linkou Chang Gung Memorial Hospital
  facility: 
  status: Recruiting
  contact: 
  country: Taiwan
  responsible party type: Principal Investigator
  investigator affiliation: Chang Gung Memorial Hospital
  investigator full name: Wei-Ting Chen
  investigator title: Director, Chang Gung Memorial Hospital
  mesh term: Carcinoma
  mesh term: Carcinoma, Hepatocellular
  sharing ipd: No