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/NCT06008119</url>
    </required_header>
    <id_info>
      <org_study_id>HL-085-304</org_study_id>
      <nct_id>NCT06008119</nct_id>
    </id_info>
    <brief_title>Efficacy and Safety of Tunlametinib Plus Vemurafenib in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer</brief_title>
    <official_title>A Multicenter, Randomized, Open-label, Phase 3 Study to Evaluate the Efficacy and Safety of Tunlametinib Plus Vemurafenib in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Shanghai Kechow Pharma, Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Shanghai Kechow Pharma, Inc.</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>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a multicenter, randomized, open-label, 3-arm Phase 3 study&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a multicenter, randomized, open-label, 3-arm Phase 3 study to evaluate Tunlamatinib&#xD;
        plus Vemurafenib versus Investigator's choice of Chemotherapy based treatment as controls in&#xD;
        patients with BRAFV600E mutant Metastatic Colorectal Cancer (CRC) whose disease has&#xD;
        progressed after 1 or more prior regimens in the metastatic setting.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 24, 2023</start_date>
    <completion_date type="Anticipated">December 24, 2026</completion_date>
    <primary_completion_date type="Anticipated">December 24, 2026</primary_completion_date>
    <phase>Phase 3</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>Progression-free Survival (PFS)</measure>
      <time_frame>up to 12 months</time_frame>
      <description>defined as the time from first dose to the earliest documented disease progression or death due to any cause</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall Survival（OS）</measure>
      <time_frame>up to 12 months</time_frame>
      <description>defined as the time from the date of taking drugs to the date of death due to any cause</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Response Rate（ORR）</measure>
      <time_frame>up to 12 months</time_frame>
      <description>Defined as the proportion of subjects with an optimal response of CR or PR over the course of the study from enrollment to disease progression</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Response（DOR）</measure>
      <time_frame>up to 12 months</time_frame>
      <description>Defined as the time from the first CR or PR evaluation of tumor efficacy to the first occurrence of PD or death from any cause (whichever occurs first)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease control rate (DCR)</measure>
      <time_frame>up to 12 months</time_frame>
      <description>roportion of subjects with response defined as CR, PR, and SD throughout the study from subjects first dose to disease progression or death</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">165</enrollment>
    <condition>Colorectal Cancer Metastatic</condition>
    <arm_group>
      <arm_group_label>Experimental</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Tunlamatinib plus Vemurafenib</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Investigators' choice</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tunlametinib plus Vemurafenib</intervention_name>
      <description>12mg BID Tunlametinib+720mg BID Vemurafenib</description>
      <arm_group_label>Experimental</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Doublets Chemotherapy ± Bevacizumab or Doublets Chemotherapy ± Cetuximab</intervention_name>
      <description>According to investigators' suggestion</description>
      <arm_group_label>Control</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Inclusion Criteria:&#xD;
  &#xD;
                 1. Before study entry, written informed consent must be obtained from the patient&#xD;
                    prior to performing any study-related procedures.&#xD;
  &#xD;
                 2. Male or female patients with 18 to 70 years of age at time of informed consent;&#xD;
  &#xD;
                 3. Histological or cytologically confirmed metastatic CRC&#xD;
  &#xD;
                 4. Presence of BRAFV600E in tumor tissue as previously determined by a local assay&#xD;
                    at any time prior to Screening or by the central laboratory (BRAFV600 is&#xD;
                    permitted)&#xD;
  &#xD;
                 5. Able to provide a sufficient amount of representative tumor specimen (primary or&#xD;
                    metastatic, archival or newly obtained) for confirmatory central laboratory&#xD;
                    testing of BRAF mutation status.&#xD;
  &#xD;
                 6. Progression of disease after 1 or more prior regimens in the metastatic setting&#xD;
  &#xD;
                 7. At least 1 site of radiographically measurable disease by RECIST 1.1&#xD;
  &#xD;
                 8. Eastern Cooperative Oncology Group (ECOG) Performance Status(PS) of 0 to 1;&#xD;
  &#xD;
                 9. Life expectancy ≥ 3 months;&#xD;
  &#xD;
                10. Can swallow the medicine,&#xD;
  &#xD;
                11. Adequate hematologic, renal, cardiac and liver function as defined by laboratory&#xD;
                    values performed within 7 days prior to initiation of dosing:&#xD;
  &#xD;
                12. Be willing and able to complete all the study procedures and follow-up&#xD;
                    examinations.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Exclusion Criteria:&#xD;
  &#xD;
                 1. Prior treatment with any BRAF and MEK inhibitor;&#xD;
  &#xD;
                 2. Known contraindication to receive the treatment of control arm (according to&#xD;
                    latest PI).&#xD;
  &#xD;
                 3. Symptomatic brain metastasis or leptomeningeal disease&#xD;
  &#xD;
                 4. History of chronic inflammatory bowel disease or Crohn's disease requiring&#xD;
                    medical intervention (immunomodulatory or immunosuppressive medications or&#xD;
                    surgery) ≤12 months prior to randomization&#xD;
  &#xD;
                 5. Known history of acute or chronic pancreatitis&#xD;
  &#xD;
                 6. Uncontrolled GI bleeding, Dysphagia，refractory nausea, vomiting, small bowel&#xD;
                    resection or any other gastrointestinal ailment that would preclude study drug&#xD;
                    absorption.&#xD;
  &#xD;
                 7. Serious cardiovascular disease , including uncontrolled congestive heart failure,&#xD;
                    uncontrolled hypertension, cardiac ischemia, myocardial infarction, and severe&#xD;
                    cardiac arrhythmia , deep vein thrombosis or pulmonary emboli or cerebrovascular&#xD;
                    events ≤ 6 months prior to starting study treatment;&#xD;
  &#xD;
                 8. History or current evidence of retinal vein occlusion or current risk factors for&#xD;
                    retinal vein occlusion (e.g., uncontrolled glaucoma or ocular hypertension,&#xD;
                    history of hyperviscosity or hypercoagulability syndromes)&#xD;
  &#xD;
                 9. Concurrent neuromuscular disorder that is associated with the potential of&#xD;
                    elevated creatine (phosphor)kinase (CK) (e.g., inflammatory myopathies, muscular&#xD;
                    dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)&#xD;
  &#xD;
                10. Uncontrolled blood pressure despite medical treatment&#xD;
  &#xD;
                11. Concurrent or previous other malignancy within 5 years of study entry, except&#xD;
                    cured basal or squamous cell skin cancer, superficial bladder cancer, prostate&#xD;
                    intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive&#xD;
                    or indolent malignancy&#xD;
  &#xD;
                12. Residual common terminology criteria for adverse events (CTCAE) ≥ Grade 2&#xD;
                    toxicity from any prior anticancer therapy, with the exception of Grade 2&#xD;
                    alopecia or Grade 2 neuropathy&#xD;
  &#xD;
                13. Anti-HIV(+) , Anti-TP( +); Active hepatitis B or hepatitis C infection …….&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 8, 2023</study_first_submitted>
    <study_first_submitted_qc>August 15, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 23, 2023</study_first_posted>
    <last_update_submitted>August 15, 2023</last_update_submitted>
    <last_update_submitted_qc>August 15, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 23, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>BRAFV600E mutant</keyword>
    <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>Bevacizumab</mesh_term>
      <mesh_term>Cetuximab</mesh_term>
      <mesh_term>Vemurafenib</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/NCT06008119
  org study id: HL-085-304
  nct id: NCT06008119
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This is a multicenter, randomized, open-label, 3-arm Phase 3 study
  This is a multicenter, randomized, open-label, 3-arm Phase 3 study to evaluate Tunlamatinib
        plus Vemurafenib versus Investigator's choice of Chemotherapy based treatment as controls in
        patients with BRAFV600E mutant Metastatic Colorectal Cancer (CRC) whose disease has
        progressed after 1 or more prior regimens in the metastatic setting.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Progression-free Survival (PFS)
  time frame: up to 12 months
  description: defined as the time from first dose to the earliest documented disease progression or death due to any cause
  measure: Overall Survival（OS）
  time frame: up to 12 months
  description: defined as the time from the date of taking drugs to the date of death due to any cause
  measure: Overall Response Rate（ORR）
  time frame: up to 12 months
  description: Defined as the proportion of subjects with an optimal response of CR or PR over the course of the study from enrollment to disease progression
  measure: Duration of Response（DOR）
  time frame: up to 12 months
  description: Defined as the time from the first CR or PR evaluation of tumor efficacy to the first occurrence of PD or death from any cause (whichever occurs first)
  measure: Disease control rate (DCR)
  time frame: up to 12 months
  description: roportion of subjects with response defined as CR, PR, and SD throughout the study from subjects first dose to disease progression or death
  arm group label: Experimental
  arm group type: Experimental
  description: Tunlamatinib plus Vemurafenib
  arm group label: Control
  arm group type: Active Comparator
  description: Investigators' choice
  intervention type: Drug
  intervention name: Tunlametinib plus Vemurafenib
  description: 12mg BID Tunlametinib+720mg BID Vemurafenib
  arm group label: Experimental
  intervention type: Drug
  intervention name: Doublets Chemotherapy ± Bevacizumab or Doublets Chemotherapy ± Cetuximab
  description: According to investigators' suggestion
  arm group label: Control
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 70 Years
  healthy volunteers: No
  responsible party type: Sponsor
  mesh term: Colorectal Neoplasms
  mesh term: Bevacizumab
  mesh term: Cetuximab
  mesh term: Vemurafenib
  sharing ipd: No