<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/NCT04415320</url>
  </required_header>
  <id_info>
    <org_study_id>BTP-42324-IIT</org_study_id>
    <nct_id>NCT04415320</nct_id>
  </id_info>
  <brief_title>X-396 (Ensartinib) Capsules in ALK-Positive NSCLC Patients With Brain Metastases</brief_title>
  <official_title>Efficacy and Safety of X-396 (Ensartinib) in ALK-Positive NSCLC Patients With Brain Metastases: A Phase Ⅱ, Open-Label, Single Arm, Multicenter Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Betta Pharmaceuticals Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fudan University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Betta Pharmaceuticals Co., Ltd.</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>
      To assess efficacy and safety of oral X-396 (Ensartinib) capsule in Chinese ALK-positive&#xD;
      NSCLC patients with brain metastases, eligible patients will be enrolled with objective&#xD;
      responses being primary outcome measures.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this phase Ⅱ, open-label, single arm, multicenter study, efficacy and safety of oral X-396&#xD;
      capsule (Ensartinib) in 37 Chinese ALK-positive NSCLC patients with brain metastases will be&#xD;
      assessed. Eligible patients will receive 225mg X-396 capsules once daily and objective&#xD;
      responses of brain metastasis based on investigator assessment according to Response&#xD;
      Assessment in Neuro-Oncology (RANO) are primary outcome measures.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 21, 2019</start_date>
  <completion_date type="Anticipated">June 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Intracranial objective response rate (iORR) based on investigator assessment according to RNAO-BM.</measure>
    <time_frame>12 weeks</time_frame>
    <description>iORR per RANO-BM calculated as the proportion of patients with a best intracranial overall response defined as complete response (CR) or partial response (PR), based on investigator assessment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease control rate based on intracranial response (iDCR) according to RANO-BM.</measure>
    <time_frame>12 weeks</time_frame>
    <description>Defined as the percentage of patients who have achieved intracranial overall response of CR, PR and stable disease (SD), assessed by investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival based on intracranial response (iPFS) according to RANO-BM</measure>
    <time_frame>36 months</time_frame>
    <description>Defined as time from first dose of X-396 capsule to intracranial disease progression or death due to any causes, assessed by investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression based on intracranial response (iTTP) according to RANO-BM.</measure>
    <time_frame>36 months</time_frame>
    <description>Defined as time from first dose of X-396 capsule to intracranial disease progression, assessed by investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response based on intracranial response (iDOR) according to RANO-BM.</measure>
    <time_frame>36 months</time_frame>
    <description>Defined as time from documentation of intracranial response (CR or PR) to intracranial disease progression or death, assessed by investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intracranial objective response rate (iORR) based on intracranial response according to RECIST 1.1.</measure>
    <time_frame>12 weeks</time_frame>
    <description>iORR per RECIST 1.1 calculated as the proportion of patients with a best intracranial overall response defined as complete response (CR) or partial response (PR), based on investigator assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate based on intracranial response (iDCR) according to RECIST 1.1</measure>
    <time_frame>12 weeks</time_frame>
    <description>Defined as the percentage of patients who have achieved intracranial overall response of CR, PR and stable disease (SD), assessed by investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival based on intracranial response (iPFS) according to RECIST 1.1</measure>
    <time_frame>36 months</time_frame>
    <description>Defined as time from first dose of X-396 capsule to intracranial disease progression or death due to any causes, assessed by investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression based on intracranial response (iTTP) according to RECIST 1.1</measure>
    <time_frame>36 months</time_frame>
    <description>Defined as time from first dose of X-396 capsule to intracranial disease progression, assessed by investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR) based on overall response according to RECIST 1.1.</measure>
    <time_frame>12 weeks</time_frame>
    <description>ORR per RECIST 1.1 calculated as the proportion of patients with a best overall response defined as complete response (CR) or partial response (PR), based on investigator assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate based on overall response (DCR) according to RECIST 1.1</measure>
    <time_frame>12 weeks</time_frame>
    <description>Defined as the percentage of patients who have achieved overall response of CR, PR and stable disease (SD), assessed by investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival based on overall response (PFS) according to RECIST 1.1</measure>
    <time_frame>36 months</time_frame>
    <description>Defined as time from first dose of X-396 capsule to overall disease progression or death due to any causes, assessed by investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression based on overall response (TTP) according to RECIST 1.1</measure>
    <time_frame>36 months</time_frame>
    <description>Defined as time from first dose of X-396 capsule to overall disease progression, assessed by investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>36 months</time_frame>
    <description>Defined as time from first dose of X-396 to death due to any causes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of patients experiencing adverse events.</measure>
    <time_frame>36 months</time_frame>
    <description>Incidence of adverse events occurred during the study (from the timeoint of signing a informed consent form to 30days after the end of trial) .</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">37</enrollment>
  <condition>Lung Cancer, Nonsmall Cell</condition>
  <condition>Brain Metastases</condition>
  <arm_group>
    <arm_group_label>X-396(Ensartinib) Capsule</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>X-396(Ensartinib)</intervention_name>
    <description>All consented, enrolled, eligible patients receive X-396 capsules, 225mg once daily.</description>
    <arm_group_label>X-396(Ensartinib) Capsule</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Female or male, 18 years of age or older&#xD;
&#xD;
          2. Histologically or cytologically confirmed locally advance or recurrent/metastatic&#xD;
             NSCLC that was positive for ALK mutations.&#xD;
&#xD;
          3. Contrast-enhanced MRI or CT confirmed parenchymal brain metastases with at least one&#xD;
             measurable lesion (according to RANO and RECIST 1.1), which was not previously treated&#xD;
             with radiotherapy.&#xD;
&#xD;
          4. At most once treated with chemotherapy, which must have been completed at least 4&#xD;
             weeks before the initiation of study treatment. Any adverse events related to previous&#xD;
             chemotherapy treatment have disappeared.&#xD;
&#xD;
          5. A Karnofsky Performance Status score of at least 60.&#xD;
&#xD;
          6. An expected survival time of at least 12 weeks.&#xD;
&#xD;
          7. Adequate organ functions.&#xD;
&#xD;
          8. Drug related toxicities has been relieved to grade 1 (based on NCI CTCAE v4.03),&#xD;
             except for hair loss.&#xD;
&#xD;
          9. Being willing and able to comply with scheduled visits, treatment plans, laboratory&#xD;
             tests and other study procedures.&#xD;
&#xD;
         10. Signed and dated informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Currently under treatment of other systemic anti-cancer therapies.&#xD;
&#xD;
          2. Evidence of active malignancy within last 5 years.&#xD;
&#xD;
          3. Patients who participated in other clinical trials within last 4 weeks before the&#xD;
             initiation of study treatment.&#xD;
&#xD;
          4. Patients who received surgery or immunotherapy within last 4 weeks before the&#xD;
             initiation of study treatment.&#xD;
&#xD;
          5. Patients who need to receive drugs which are potent CYP3A4 inhibitors or inducers&#xD;
             within last 2 weeks before the initiation of study treatment and during the study.&#xD;
&#xD;
          6. Patients who previously received organ transplantation or stem cell transplantation.&#xD;
&#xD;
          7. Patients with clinically significant cardiovascular diseases.&#xD;
&#xD;
          8. Patients with active gastrointestinal diseases or other conditions that will interfere&#xD;
             significantly with the absorption, distribution, metabolism or excretion of study&#xD;
             medication.&#xD;
&#xD;
          9. Patients with interstitial lung disease history or signs of active interstitial lung&#xD;
             disease.&#xD;
&#xD;
         10. Patients with known allergy or delayed hypersensitivity reaction to study drug or its&#xD;
             excipients.&#xD;
&#xD;
         11. Pregnant and lactating women.&#xD;
&#xD;
         12. Patients with other illness or medical conditions potentially interfering with the&#xD;
             study treatment.&#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>Jianhua Chang</last_name>
    <phone>8613916619284</phone>
    <email>changjianhua@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Fudan University Shanghai Cancer Center</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jianhua Chang</last_name>
      <phone>8613916619284</phone>
      <email>changjianhua@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 29, 2020</study_first_submitted>
  <study_first_submitted_qc>May 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</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 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>NSCLC, Brain metastases, ALK mutations, X-396 (Ensartinib)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Brain Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ensartinib</mesh_term>
  </intervention_browse>
  <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/NCT04415320
org study id: BTP-42324-IIT
nct id: NCT04415320
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To assess efficacy and safety of oral X-396 (Ensartinib) capsule in Chinese ALK-positive
      NSCLC patients with brain metastases, eligible patients will be enrolled with objective
      responses being primary outcome measures.
In this phase Ⅱ, open-label, single arm, multicenter study, efficacy and safety of oral X-396
      capsule (Ensartinib) in 37 Chinese ALK-positive NSCLC patients with brain metastases will be
      assessed. Eligible patients will receive 225mg X-396 capsules once daily and objective
      responses of brain metastasis based on investigator assessment according to Response
      Assessment in Neuro-Oncology (RANO) are primary outcome measures.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Intracranial objective response rate (iORR) based on investigator assessment according to RNAO-BM.
time frame: 12 weeks
description: iORR per RANO-BM calculated as the proportion of patients with a best intracranial overall response defined as complete response (CR) or partial response (PR), based on investigator assessment.
measure: Disease control rate based on intracranial response (iDCR) according to RANO-BM.
time frame: 12 weeks
description: Defined as the percentage of patients who have achieved intracranial overall response of CR, PR and stable disease (SD), assessed by investigator.
measure: Progression-free survival based on intracranial response (iPFS) according to RANO-BM
time frame: 36 months
description: Defined as time from first dose of X-396 capsule to intracranial disease progression or death due to any causes, assessed by investigator.
measure: Time to progression based on intracranial response (iTTP) according to RANO-BM.
time frame: 36 months
description: Defined as time from first dose of X-396 capsule to intracranial disease progression, assessed by investigator.
measure: Duration of response based on intracranial response (iDOR) according to RANO-BM.
time frame: 36 months
description: Defined as time from documentation of intracranial response (CR or PR) to intracranial disease progression or death, assessed by investigator.
measure: Intracranial objective response rate (iORR) based on intracranial response according to RECIST 1.1.
time frame: 12 weeks
description: iORR per RECIST 1.1 calculated as the proportion of patients with a best intracranial overall response defined as complete response (CR) or partial response (PR), based on investigator assessment.
measure: Disease control rate based on intracranial response (iDCR) according to RECIST 1.1
time frame: 12 weeks
description: Defined as the percentage of patients who have achieved intracranial overall response of CR, PR and stable disease (SD), assessed by investigator.
measure: Progression-free survival based on intracranial response (iPFS) according to RECIST 1.1
time frame: 36 months
description: Defined as time from first dose of X-396 capsule to intracranial disease progression or death due to any causes, assessed by investigator.
measure: Time to progression based on intracranial response (iTTP) according to RECIST 1.1
time frame: 36 months
description: Defined as time from first dose of X-396 capsule to intracranial disease progression, assessed by investigator.
measure: Objective response rate (ORR) based on overall response according to RECIST 1.1.
time frame: 12 weeks
description: ORR per RECIST 1.1 calculated as the proportion of patients with a best overall response defined as complete response (CR) or partial response (PR), based on investigator assessment.
measure: Disease control rate based on overall response (DCR) according to RECIST 1.1
time frame: 12 weeks
description: Defined as the percentage of patients who have achieved overall response of CR, PR and stable disease (SD), assessed by investigator.
measure: Progression-free survival based on overall response (PFS) according to RECIST 1.1
time frame: 36 months
description: Defined as time from first dose of X-396 capsule to overall disease progression or death due to any causes, assessed by investigator.
measure: Time to progression based on overall response (TTP) according to RECIST 1.1
time frame: 36 months
description: Defined as time from first dose of X-396 capsule to overall disease progression, assessed by investigator.
measure: Overall survival (OS)
time frame: 36 months
description: Defined as time from first dose of X-396 to death due to any causes.
measure: Incidence of patients experiencing adverse events.
time frame: 36 months
description: Incidence of adverse events occurred during the study (from the timeoint of signing a informed consent form to 30days after the end of trial) .
arm group label: X-396(Ensartinib) Capsule
arm group type: Experimental
intervention type: Drug
intervention name: X-396(Ensartinib)
description: All consented, enrolled, eligible patients receive X-396 capsules, 225mg once daily.
arm group label: X-396(Ensartinib) Capsule
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jianhua Chang
phone: 8613916619284
email: changjianhua@163.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
mesh term: Brain Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Ensartinib
sharing ipd: No