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/NCT06039202</url>
    </required_header>
    <id_info>
      <org_study_id>HS-CA102N-103</org_study_id>
      <nct_id>NCT06039202</nct_id>
    </id_info>
    <brief_title>Phase 2 Study of CA102N Combined With TAS-102 Compared to Bevacizumab Combined With TAS-102 in Subjects With Relapsed and/or Refractory Metastatic Colorectal Cancer</brief_title>
    <official_title>A Phase 2, Randomized, Open Label Study to Evaluate Efficacy, Safety, and Tolerability of CA102N Combined With Trifluridine/Tipiracil (TAS-102) Compared to Bevacizumab Combined With TAS-102 in Subjects With Metastatic Colorectal Cancer (mCRC) Who Failed the Standard Treatment</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Holy Stone Healthcare Co., Ltd</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Holy Stone Healthcare Co., Ltd</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>Yes</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>
        HS-CA102N-103 is a Phase 2, randomized, open label study to evaluate efficacy, safety, and&#xD;
        tolerability of CA102N combined with trifluridine/tipiracil (TAS-102) compared to bevacizumab&#xD;
        combined with TAS-102 in subjects with metastatic colorectal cancer (mCRC) who failed the&#xD;
        standard treatment (for eg, cancer that has relapsed after or is refractory to&#xD;
        fluoropyrimidine, oxaliplatin and irinotecan-based chemotherapy).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        HS-CA102N-103 is a Phase 2, randomized, open label study to evaluate efficacy, safety, and&#xD;
        tolerability of CA102N combined with trifluridine/tipiracil (TAS-102) compared to bevacizumab&#xD;
        combined with TAS-102 in subjects with metastatic colorectal cancer (mCRC) who failed the&#xD;
        standard treatment (for eg, cancer that has relapsed after or is refractory to&#xD;
        fluoropyrimidine, oxaliplatin and irinotecan-based chemotherapy).&#xD;
  &#xD;
        In this study, the safety, tolerability, and PFS of CA102N in combination with TAS-102&#xD;
        compared to bevacizumab combined with TAS-102 will be evaluated in up to 100 subjects with&#xD;
        metastatic colorectal cancer who have previously received fluoropyrimidine, oxaliplatin, and&#xD;
        irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) biological&#xD;
        therapy, and if RAS wild-type mCRC, an anti-epidermal growth factor receptor (EGFR) therapy.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 2024</start_date>
    <completion_date type="Anticipated">October 2025</completion_date>
    <primary_completion_date type="Anticipated">February 2025</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>
      <intervention_model_description>Up to 100 subjects will be enrolled in this study (including drop-out subjects), with 50 subjects assigned to each treatment arm.&#xD;
  For arm 1, subjects will receive the assigned dose level of CA102N in combination with trifluridine/tipiracil (TAS-102). For Arm 2, subjects will receive bevacizumab in combination with trifluridine/tipiracil (TAS-102)</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>To evaluate the efficacy of CA102N in combination with trifluridine/tipiracil (TAS-102) by progression free survival (PFS) rate.</measure>
      <time_frame>16 weeks after first treatment.</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of subjects with treatment-related adverse events as assessed by NCI-CTCAE v5.0</measure>
      <time_frame>one year after first treatment.</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Disease control rate (DCR)</measure>
      <time_frame>16 weeks after first treatment.</time_frame>
      <description>To evaluate the efficacy of CA102N in combination with trifluridine/tipiracil (TAS-102) by disease control rate.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall response rate (ORR)</measure>
      <time_frame>16 weeks after first treatment.</time_frame>
      <description>To evaluate the efficacy of CA102N in combination with trifluridine/tipiracil (TAS-102) by overall response rate.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Maximum Plasma Concentration [Cmax] of CA102N when used in combination with trifluridine/tipiracil (TAS-102)</measure>
      <time_frame>16 weeks after first treatment.</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To evaluate the efficacy of CA102N in combination with trifluridine/tipiracil (TAS-102) by overall survival (OS).</measure>
      <time_frame>one year after first treatment.</time_frame>
    </secondary_outcome>
    <other_outcome>
      <measure>Protein expression level of pharmacodynamic biomarkers</measure>
      <time_frame>16 weeks after first treatment.</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Quality of life measured by European Organization for the research and treatment of cancer quality of life questionnaire (EORTC QLQ-C30).</measure>
      <time_frame>one year after first treatment.</time_frame>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">100</enrollment>
    <condition>Metastatic Colorectal Cancer</condition>
    <arm_group>
      <arm_group_label>CA102N plus Trifluridine/tipiracil (TAS-102)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>CA102N administered as 0.72 mg/kg of nimesulide equivalents on Days 1 and 15 of each 28-day cycle in combination with TAS-102 at 35 mg/m2/dose orally twice daily (BID) on Days 1 through 5 and Days 8 through 12 of each 28-day cycle. Administration sequence will be CA102N then TAS-102 (IV then oral)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Bevacizumab plus Trifluridine/tipiracil (TAS-102)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>bevacizumab 5 mg/kg on Days 1 and 15 of each 28-day cycle in combination with 35 mg/m2 of TAS-102 orally twice daily (BID) on Days 1 through 5 and Days 8 through 12 of each 28-day cycle. Administration sequence will be bevacizumab then TAS-102 (IV then oral)</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>CA102N</intervention_name>
      <description>CA102N is a covalently bound conjugate of the biological polymer sodium hyaluronate (NaHA) and nimesulide (Nim)</description>
      <arm_group_label>CA102N plus Trifluridine/tipiracil (TAS-102)</arm_group_label>
      <other_name>Nim-HA cinjugate</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>TAS-102</intervention_name>
      <description>TAS-102 is a cytotoxic combination treatment of 2 drugs: trifluridine, a thymidine-based nucleoside analogue, and tipiracil an inhibitor of thymidine phosphorylase.</description>
      <arm_group_label>Bevacizumab plus Trifluridine/tipiracil (TAS-102)</arm_group_label>
      <arm_group_label>CA102N plus Trifluridine/tipiracil (TAS-102)</arm_group_label>
      <other_name>Trifluridine/tipiracil</other_name>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Bevacizumab</intervention_name>
      <description>Bevacizumab recombinant humanized monoclonal antibody that binds and neutralizes circulating vascular endothelial growth factor (VEGF)-A.</description>
      <arm_group_label>Bevacizumab plus Trifluridine/tipiracil (TAS-102)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Adults aged ≥20 years in Taiwan, and Korea, or those aged ≥18 years in the US, at the&#xD;
               time the ICFs are signed. (Please follow local regulatory requirements if the legal&#xD;
               age of consent for study participation is different).&#xD;
  &#xD;
            -  Have relapsed after, intolerant to, or are refractory to fluoropyrimidine-,&#xD;
               oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and&#xD;
               if RAS wild-type, an anti-EGFR therapy.&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group performance status 0 to 1.&#xD;
  &#xD;
            -  Presence of at least one measurable lesion (minimum 10 mm) assessed by the&#xD;
               Investigator per RECIST version 1.1. Lesions situated in a previously irradiated area&#xD;
               are considered measurable if progression has been demonstrated in such lesions after&#xD;
               the end of radiotherapy.&#xD;
  &#xD;
            -  Has a life expectancy of ≥3 months.&#xD;
  &#xD;
            -  Women of childbearing potential and men with partners of childbearing potential must&#xD;
               agree to use a highly effective means of contraception from study entry through at&#xD;
               least 6 months after the last dose of CA102N.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  History of hypersensitivity or hepatotoxic reactions to nimesulide or to any&#xD;
               excipient.&#xD;
  &#xD;
            -  History or presence of a bleeding tendency or disorder.&#xD;
  &#xD;
            -  History of gastrointestinal bleed or perforation related to previous nonsteroidal&#xD;
               anti-inflammatory drugs (NSAIDs) or bevacizumab.&#xD;
  &#xD;
            -  Presence or history of recurrent peptic ulcer or hemorrhage (2 or more distinct&#xD;
               episodes of proven ulceration or bleeding).&#xD;
  &#xD;
            -  History of cerebrovascular or other active bleeding.&#xD;
  &#xD;
            -  Myocardial infarction within the last 12 months prior to the first dose of study drug,&#xD;
               severe/unstable angina, symptomatic congestive heart failure New York Heart&#xD;
               Association Class III or IV.&#xD;
  &#xD;
            -  History of a serious cardiac arrhythmia requiring treatment. Subjects whose arrhythmia&#xD;
               is well-controlled (eg, by ablation or medical therapy) may be considered for&#xD;
               enrollment after discussion with the study medical monitor.&#xD;
  &#xD;
            -  Has had clinically significant lung disease (eg, interstitial pneumonia, interstitial&#xD;
               lung disease, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis)&#xD;
               requiring continuous systemic corticosteroid treatment for 6 months before Screening&#xD;
               or who are suspected to have such diseases by imaging at Screening.&#xD;
  &#xD;
            -  Ascites, pleural effusion, or pericardial fluid requiring drainage in last 4 weeks&#xD;
               prior to Screening, or subject who continues to have a peritoneal/pleural/pericardial&#xD;
               drainage catheter post-surgery at the time of informed consent signature.&#xD;
  &#xD;
            -  History of allogeneic transplantation requiring immunosuppressive therapy.&#xD;
  &#xD;
            -  Presence of uncontrolled infections.&#xD;
  &#xD;
            -  Known positive test for hepatitis B, hepatitis C or human immunodeficiency virus.&#xD;
               Testing is not required for protocol eligibility. Subjects who have received curative&#xD;
               therapy for HCV with no detectable viral load are not excluded.&#xD;
  &#xD;
            -  Has clinically active brain metastases, defined as untreated and symptomatic, or&#xD;
               requiring therapy with steroids or anticonvulsants to control associated symptoms.&#xD;
               Subjects with treated brain metastases that are no longer symptomatic and who require&#xD;
               no treatment with steroids and stable brain metastases at least 3 months may be&#xD;
               included in the study if they have recovered from the acute toxic effect of&#xD;
               radiotherapy.&#xD;
  &#xD;
            -  Pregnant or breast feeding or intends to become pregnant during the study.&#xD;
  &#xD;
            -  Unresolved toxicity of greater than or equal to NCI-CTCAE (version 5.0) Grade 2&#xD;
               attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation, and&#xD;
               platinum-induced peripheral neurotoxicity).&#xD;
  &#xD;
            -  Has a concomitant medical condition that would increase the risk of toxicity or&#xD;
               confine the interpretation of efficacy or safety in the opinion of the Investigator.&#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_contact>
      <last_name>Ivy Chen</last_name>
      <phone>886 2 87975966</phone>
      <phone_ext>272</phone_ext>
      <email>ivychen@hshc.com.tw</email>
    </overall_contact>
    <link>
      <url>https://pubmed.ncbi.nlm.nih.gov/36331676/</url>
      <description>The result of phase I study</description>
    </link>
    <results_reference>
      <citation>Pant S, Dragovich T, Lieu C, Jimeno A, Kundranda M, Menter D, Tchaparian E, Chen YC, Kopetz S. Phase 1 study of the safety, pharmacokinetics, and preliminary efficacy of CA102N as monotherapy and in combination with trifluridine-tipiracil in patients with locally advanced or metastatic solid tumors. Invest New Drugs. 2023 Feb;41(1):25-34. doi: 10.1007/s10637-022-01308-5. Epub 2022 Nov 4.</citation>
      <PMID>36331676</PMID>
    </results_reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 1, 2023</study_first_submitted>
    <study_first_submitted_qc>September 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 15, 2023</study_first_posted>
    <last_update_submitted>September 8, 2023</last_update_submitted>
    <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 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>Colorectal Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Trifluridine</mesh_term>
      <mesh_term>Bevacizumab</mesh_term>
    </intervention_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/NCT06039202
  org study id: HS-CA102N-103
  nct id: NCT06039202
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: No
  HS-CA102N-103 is a Phase 2, randomized, open label study to evaluate efficacy, safety, and
        tolerability of CA102N combined with trifluridine/tipiracil (TAS-102) compared to bevacizumab
        combined with TAS-102 in subjects with metastatic colorectal cancer (mCRC) who failed the
        standard treatment (for eg, cancer that has relapsed after or is refractory to
        fluoropyrimidine, oxaliplatin and irinotecan-based chemotherapy).
  HS-CA102N-103 is a Phase 2, randomized, open label study to evaluate efficacy, safety, and
        tolerability of CA102N combined with trifluridine/tipiracil (TAS-102) compared to bevacizumab
        combined with TAS-102 in subjects with metastatic colorectal cancer (mCRC) who failed the
        standard treatment (for eg, cancer that has relapsed after or is refractory to
        fluoropyrimidine, oxaliplatin and irinotecan-based chemotherapy).
  
        In this study, the safety, tolerability, and PFS of CA102N in combination with TAS-102
        compared to bevacizumab combined with TAS-102 will be evaluated in up to 100 subjects with
        metastatic colorectal cancer who have previously received fluoropyrimidine, oxaliplatin, and
        irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) biological
        therapy, and if RAS wild-type mCRC, an anti-epidermal growth factor receptor (EGFR) therapy.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Up to 100 subjects will be enrolled in this study (including drop-out subjects), with 50 subjects assigned to each treatment arm.
  For arm 1, subjects will receive the assigned dose level of CA102N in combination with trifluridine/tipiracil (TAS-102). For Arm 2, subjects will receive bevacizumab in combination with trifluridine/tipiracil (TAS-102)
  primary purpose: Treatment
  masking: None (Open Label)
  measure: To evaluate the efficacy of CA102N in combination with trifluridine/tipiracil (TAS-102) by progression free survival (PFS) rate.
  time frame: 16 weeks after first treatment.
  measure: Number of subjects with treatment-related adverse events as assessed by NCI-CTCAE v5.0
  time frame: one year after first treatment.
  measure: Disease control rate (DCR)
  time frame: 16 weeks after first treatment.
  description: To evaluate the efficacy of CA102N in combination with trifluridine/tipiracil (TAS-102) by disease control rate.
  measure: Overall response rate (ORR)
  time frame: 16 weeks after first treatment.
  description: To evaluate the efficacy of CA102N in combination with trifluridine/tipiracil (TAS-102) by overall response rate.
  measure: Maximum Plasma Concentration [Cmax] of CA102N when used in combination with trifluridine/tipiracil (TAS-102)
  time frame: 16 weeks after first treatment.
  measure: To evaluate the efficacy of CA102N in combination with trifluridine/tipiracil (TAS-102) by overall survival (OS).
  time frame: one year after first treatment.
  measure: Protein expression level of pharmacodynamic biomarkers
  time frame: 16 weeks after first treatment.
  measure: Quality of life measured by European Organization for the research and treatment of cancer quality of life questionnaire (EORTC QLQ-C30).
  time frame: one year after first treatment.
  arm group label: CA102N plus Trifluridine/tipiracil (TAS-102)
  arm group type: Experimental
  description: CA102N administered as 0.72 mg/kg of nimesulide equivalents on Days 1 and 15 of each 28-day cycle in combination with TAS-102 at 35 mg/m2/dose orally twice daily (BID) on Days 1 through 5 and Days 8 through 12 of each 28-day cycle. Administration sequence will be CA102N then TAS-102 (IV then oral)
  arm group label: Bevacizumab plus Trifluridine/tipiracil (TAS-102)
  arm group type: Active Comparator
  description: bevacizumab 5 mg/kg on Days 1 and 15 of each 28-day cycle in combination with 35 mg/m2 of TAS-102 orally twice daily (BID) on Days 1 through 5 and Days 8 through 12 of each 28-day cycle. Administration sequence will be bevacizumab then TAS-102 (IV then oral)
  intervention type: Drug
  intervention name: CA102N
  description: CA102N is a covalently bound conjugate of the biological polymer sodium hyaluronate (NaHA) and nimesulide (Nim)
  arm group label: CA102N plus Trifluridine/tipiracil (TAS-102)
  other name: Nim-HA cinjugate
  intervention type: Drug
  intervention name: TAS-102
  description: TAS-102 is a cytotoxic combination treatment of 2 drugs: trifluridine, a thymidine-based nucleoside analogue, and tipiracil an inhibitor of thymidine phosphorylase.
  arm group label: Bevacizumab plus Trifluridine/tipiracil (TAS-102)
  arm group label: CA102N plus Trifluridine/tipiracil (TAS-102)
  other name: Trifluridine/tipiracil
  intervention type: Biological
  intervention name: Bevacizumab
  description: Bevacizumab recombinant humanized monoclonal antibody that binds and neutralizes circulating vascular endothelial growth factor (VEGF)-A.
  arm group label: Bevacizumab plus Trifluridine/tipiracil (TAS-102)
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Ivy Chen
  phone: 886 2 87975966
  phone ext: 272
  email: ivychen@hshc.com.tw
  url: https://pubmed.ncbi.nlm.nih.gov/36331676/
  description: The result of phase I study
  citation: Pant S, Dragovich T, Lieu C, Jimeno A, Kundranda M, Menter D, Tchaparian E, Chen YC, Kopetz S. Phase 1 study of the safety, pharmacokinetics, and preliminary efficacy of CA102N as monotherapy and in combination with trifluridine-tipiracil in patients with locally advanced or metastatic solid tumors. Invest New Drugs. 2023 Feb;41(1):25-34. doi: 10.1007/s10637-022-01308-5. Epub 2022 Nov 4.
  PMID: 36331676
  responsible party type: Sponsor
  mesh term: Colorectal Neoplasms
  mesh term: Trifluridine
  mesh term: Bevacizumab
  sharing ipd: No