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/NCT06008106</url>
    </required_header>
    <id_info>
      <org_study_id>HL-085-301</org_study_id>
      <nct_id>NCT06008106</nct_id>
    </id_info>
    <brief_title>Comparing Tunlametinib Capsules and Combination Chemotherapy in Advanced NRAS-mutant Melanoma</brief_title>
    <official_title>Efficacy and Safety of Tunlametinib Capsules Versus Combination Chemotherapy of Investigator's Choice in Advanced NRAS-mutant Melanoma Patients Who Had Previously Received Immunotherapy</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, two-arm, open-label, randomized controlled phase III clinical trial to&#xD;
        evaluate the efficacy and safety of tunlametinib capsule in comparison with the combination&#xD;
        chemotherapy of investigator's choice in advanced melanoma patients with NRAS mutation who&#xD;
        have received immunotherapy before. Subjects were stratified according to the baseline&#xD;
        lactate dehydrogenase level and chemotherapy.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        A total of 165 subjects will be included and randomly assigned to the corresponding treatment&#xD;
        group in a 2:1 ratio by Interactive Web Response System（IWRS）.&#xD;
  &#xD;
        Experimental group: subjects received continuous administration of tunlametinib capsules&#xD;
        every 28 days, and the study treatment was terminated until intolerable toxicity, disease&#xD;
        progression, withdrawal of informed consent, death, or when the risk outweigh the benefit&#xD;
        assessed by the investigators, or when the study was terminated (whichever occurred earlier).&#xD;
  &#xD;
        Control group: subjects received the combination chemotherapy (paclitaxel +carboplatin, or&#xD;
        temozolomide +cisplatin, or dacarbazine +cisplatin, investigator's choice according to the&#xD;
        conditions of the subjects) every 28 days until intolerable toxicity, disease progression,&#xD;
        withdrawal of informed consent, death, or when the risk outweigh the benefit assessed by the&#xD;
        investigator or when the study was terminated (whichever occurred earlier).&#xD;
  &#xD;
        Efficacy was evaluated by independent radiology review committee and the investigator,&#xD;
        respectively.&#xD;
  &#xD;
        Within 30 days after the last administration of the study drug, the safety of the subjects&#xD;
        will also be closely monitored and recorded. After safety visit or the last administration of&#xD;
        the study drug (whichever occurs later), subject survival follow-up is conducted every 12&#xD;
        weeks to confirm the survival status and record new anti-tumor treatment until death, lost to&#xD;
        follow-up, withdrawal of informed consent, or the end of this study (whichever occurs&#xD;
        earlier).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 22, 2023</start_date>
    <completion_date type="Anticipated">September 22, 2027</completion_date>
    <primary_completion_date type="Anticipated">September 22, 2027</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>Duration of response(DOR)</measure>
      <time_frame>up to 12 months</time_frame>
      <description>Duration of response is defined as subjects who show a confirmed clinical response (CR) or partial response (PR), the time from first documented evidence of CR or PR until the first documented sign of disease progression or death</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease control rate(DCR)</measure>
      <time_frame>up to 12 months</time_frame>
      <description>Proportion 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>Melanoma</condition>
    <arm_group>
      <arm_group_label>tunlametinib</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Drug tunlametinib will be administered as 12mg BID</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Assigned Interventions</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>combination chemotherapy</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>tunlametinib</intervention_name>
      <description>12mg BID</description>
      <arm_group_label>tunlametinib</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>paclitaxel +carboplatin, or temozolomide +cisplatin, or dacarbazine +cisplatin</intervention_name>
      <description>according to investigators' suggestion</description>
      <arm_group_label>Assigned Interventions</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. ≥ 18 years of age.&#xD;
  &#xD;
            2. Patients with unresectable stage III or metastatic IV melanoma confirmed by histology&#xD;
               or cytology.&#xD;
  &#xD;
            3. History of immunotherapy failure or could not tolerate immunotherapy&#xD;
  &#xD;
            4. NRAS mutation at baseline;.&#xD;
  &#xD;
            5. There is at least one lesion that can be evaluated as target lesions according to&#xD;
               Response Evaluation Criteria in Solid Tumors (RECIST v1.1).&#xD;
  &#xD;
            6. Eastern cooperative oncology group (ECOG) performance status of grade 0-1.&#xD;
  &#xD;
            7. Life expectancy &gt; 3 months.&#xD;
  &#xD;
            8. No major surgery (excluding baseline tumor biopsy) or major trauma occurred at least&#xD;
               4weeks prior to investigational drug administration.&#xD;
  &#xD;
            9. Left ventricular ejection fraction (LVEF) ≥ 50% within 7 days before dosing according&#xD;
               to echocardiographic findings.&#xD;
  &#xD;
           10. Key laboratory tests must be conducted within 7 days before dosing and meet the&#xD;
               inclusion criteria:&#xD;
  &#xD;
           11. Able to understand and voluntarily sign the Informed Consent Form.&#xD;
  &#xD;
           12. Patients must be willing and able to complete the study procedure and follow-up&#xD;
               examination.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Exclusion Criteria:&#xD;
  &#xD;
                 1. Having the following treatment before receiving the study drug: ① received&#xD;
                    chemotherapy, targeted therapy or other study drug treatment within 4 weeks&#xD;
                    before the first administration or within 5 half lives of the drug (whichever is&#xD;
                    longer); ② received immunotherapy and biological therapy within 4 weeks before&#xD;
                    the first administration; ③ received traditional Chinese medicines with&#xD;
                    anti-tumor activities approved by National Medical Products Administration (NMPA)&#xD;
                    within 2 weeks before the first administration.;&#xD;
  &#xD;
                 2. The toxic reactions of previous anti-tumor treatment have not been recovered;&#xD;
  &#xD;
                 3. Current use of other anti-cancer drugs.&#xD;
  &#xD;
                 4. Subjects with symptomatic or untreated brain metastasis, meningeal metastasis or&#xD;
                    spinal cord compression except for subjects with asymptomatic brain metastasis;&#xD;
  &#xD;
                 5. History of any of the following within 6 months of screening: myocardial&#xD;
                    infarction, severe/unstable angina, coronary/peripheral artery bypass grafting,&#xD;
                    symptomatic congestive heart failure, severe heart arrhythmia requiring&#xD;
                    medication, uncontrolled hypertension, cerebrovascular accident, or transient&#xD;
                    ischemic attack, diabetic ketoacidosis, deep vein thrombosis, or symptomatic&#xD;
                    pulmonary embolism.&#xD;
  &#xD;
                 6. ECG Corrected Q-T interval formula (QTcB) ≥ 480 msec (adjusted by Bazett's&#xD;
                    formula) during screening, or a history of congenital long QT syndrome.&#xD;
  &#xD;
                 7. History or current evidence of retinal diseases;&#xD;
  &#xD;
                 8. Previous or current neuromuscular diseases related to CK elevation;&#xD;
  &#xD;
                 9. Previous or current interstitial lung disease or interstitial pneumonitis;&#xD;
  &#xD;
                10. Uncontrolled concomitant diseases or infectious diseases.&#xD;
  &#xD;
                11. Bleeding symptoms of grade 3 as defined by the National Cancer Institute General&#xD;
                    Terminology Standard for Adverse Events (NCI CTCAE V5.0) within the 4 weeks prior&#xD;
                    to study initiation.&#xD;
  &#xD;
                12. Inability to swallow the capsule, refractory nausea and vomiting, malabsorption,&#xD;
                    external biliary diversion, or any small intestinal resection that would preclude&#xD;
                    adequate absorption of the study drug.&#xD;
  &#xD;
                13. Patients who are receiving and cannot discontinue regimen-prohibited intravenous&#xD;
                    or oral drugs that affect CYP isoenzymes (strong inducers and strong inhibitors&#xD;
                    of CYP2C9) at least 1 week prior to initiation of study treatment and during the&#xD;
                    study period.&#xD;
  &#xD;
                14. Patients with a history of malignancy within the past 5 years;&#xD;
  &#xD;
                15. Human immunodeficiency virus (HIV) antibody positive; syphilis antibody (anti-TP)&#xD;
                    positive; Hepatitis C virus (HCV) antibody positive and HCV RNA positive; HBsAg&#xD;
                    positive and HBV DNA positive.&#xD;
  &#xD;
                16. Patients who have been previously treated with MEK inhibitors.&#xD;
  &#xD;
                17. Patients with known hypersensitivity to investigational drug, proposed&#xD;
                    chemotherapy or their analogues.&#xD;
  &#xD;
                18. History of allogeneic bone marrow transplantation or organ transplantation.&#xD;
  &#xD;
                19. Serum pregnancy test results are positive for premenopausal female patients;&#xD;
  &#xD;
                20. Other severe, acute, or chronic clinical or psychiatric disorders or laboratory&#xD;
                    abnormalities that may increase the risk and interfere with the study results in&#xD;
                    the opinion of 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_official>
      <last_name>Hongqi Tian, phD</last_name>
      <role>Study Director</role>
      <affiliation>Shanghai Kechow Pharma, Inc.</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Zhimei Zhu, Master</last_name>
      <phone>15201345822</phone>
      <email>zhuzm@kechowpharma.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Beijing Cancer Hospital</name>
        <address>
          <city>Beijing</city>
          <state>Beijing</state>
          <zip>100142</zip>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Jun Guo, M.D.</last_name>
        <phone>+86-10-88121122</phone>
        <email>guoj307@126.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <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>Mitogen-Activated Protein Kinase Kinases</keyword>
    <keyword>NRAS</keyword>
    <keyword>Melanoma</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Melanoma</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Paclitaxel</mesh_term>
      <mesh_term>Cisplatin</mesh_term>
      <mesh_term>Carboplatin</mesh_term>
      <mesh_term>Temozolomide</mesh_term>
      <mesh_term>Dacarbazine</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/NCT06008106
  org study id: HL-085-301
  nct id: NCT06008106
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This is a multicenter, two-arm, open-label, randomized controlled phase III clinical trial to
        evaluate the efficacy and safety of tunlametinib capsule in comparison with the combination
        chemotherapy of investigator's choice in advanced melanoma patients with NRAS mutation who
        have received immunotherapy before. Subjects were stratified according to the baseline
        lactate dehydrogenase level and chemotherapy.
  A total of 165 subjects will be included and randomly assigned to the corresponding treatment
        group in a 2:1 ratio by Interactive Web Response System（IWRS）.
  
        Experimental group: subjects received continuous administration of tunlametinib capsules
        every 28 days, and the study treatment was terminated until intolerable toxicity, disease
        progression, withdrawal of informed consent, death, or when the risk outweigh the benefit
        assessed by the investigators, or when the study was terminated (whichever occurred earlier).
  
        Control group: subjects received the combination chemotherapy (paclitaxel +carboplatin, or
        temozolomide +cisplatin, or dacarbazine +cisplatin, investigator's choice according to the
        conditions of the subjects) every 28 days until intolerable toxicity, disease progression,
        withdrawal of informed consent, death, or when the risk outweigh the benefit assessed by the
        investigator or when the study was terminated (whichever occurred earlier).
  
        Efficacy was evaluated by independent radiology review committee and the investigator,
        respectively.
  
        Within 30 days after the last administration of the study drug, the safety of the subjects
        will also be closely monitored and recorded. After safety visit or the last administration of
        the study drug (whichever occurs later), subject survival follow-up is conducted every 12
        weeks to confirm the survival status and record new anti-tumor treatment until death, lost to
        follow-up, withdrawal of informed consent, or the end of this study (whichever occurs
        earlier).
  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: Duration of response(DOR)
  time frame: up to 12 months
  description: Duration of response is defined as subjects who show a confirmed clinical response (CR) or partial response (PR), the time from first documented evidence of CR or PR until the first documented sign of disease progression or death
  measure: Disease control rate(DCR)
  time frame: up to 12 months
  description: Proportion 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: tunlametinib
  arm group type: Experimental
  description: Drug tunlametinib will be administered as 12mg BID
  arm group label: Assigned Interventions
  arm group type: Active Comparator
  description: combination chemotherapy
  intervention type: Drug
  intervention name: tunlametinib
  description: 12mg BID
  arm group label: tunlametinib
  intervention type: Drug
  intervention name: paclitaxel +carboplatin, or temozolomide +cisplatin, or dacarbazine +cisplatin
  description: according to investigators' suggestion
  arm group label: Assigned Interventions
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Hongqi Tian, phD
  role: Study Director
  affiliation: Shanghai Kechow Pharma, Inc.
  last name: Zhimei Zhu, Master
  phone: 15201345822
  email: zhuzm@kechowpharma.com
  facility: 
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Melanoma
  mesh term: Paclitaxel
  mesh term: Cisplatin
  mesh term: Carboplatin
  mesh term: Temozolomide
  mesh term: Dacarbazine
  sharing ipd: No