<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/NCT03753685</url>
  </required_header>
  <id_info>
    <org_study_id>BTP-42324-IIT</org_study_id>
    <nct_id>NCT03753685</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>Fudan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Betta Pharmaceuticals Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Fudan University</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>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">December 2018</start_date>
  <completion_date type="Anticipated">October 2020</completion_date>
  <primary_completion_date type="Anticipated">July 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>Duration of response based on intracranial response (iDOR) according to RECIST 1.1</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>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>Duration of response based on overall response (DOR) according to RECIST 1.1</measure>
    <time_frame>36 months</time_frame>
    <description>Defined as time from documentation of overall response (CR or PR) to overall disease progression or death, 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>Nonsmall Cell Lung Cancer</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) Capsule</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. Histologically or cytologically confirmed locally advance or recurrent/metastatic&#xD;
             NSCLC that was positive for ALK mutations.&#xD;
&#xD;
             2. Contrast-enhanced MRI or CT confirmed parenchymal brain metastases with at least&#xD;
             one measurable lesion (according to RANO and RECIST 1.1), which was not previously&#xD;
             treated with radiotherapy.&#xD;
&#xD;
             3. 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;
             4. Female or male, 18 years of age or older 5. A Karnofsky Performance Status score of&#xD;
             at least 60. 6. An expected survival time of at least 12 weeks. 7. Adequate organ&#xD;
             functions, defined as absolute neutrophils count ≥1.5*10^9/L，platelets count&#xD;
             ≥80*10^9/L, hemoglobin concentration≥ 9 g/dL, total bilirubin ≤1.5 *ULN (upper limits&#xD;
             of normal), ALT≤2.5 *ULN, AST≤2.5 *ULN, creatinine≤1.5 *ULN.&#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. 2. Evidence of&#xD;
             active malignancy within last 5 years. 3. Patients who participated in other clinical&#xD;
             trials within last 4 weeks before the initiation of study treatment.&#xD;
&#xD;
             4. Patients who received surgery or immunotherapy within last 4 weeks before the&#xD;
             initiation of study treatment, or received radiotherapy within last 2 weeks before the&#xD;
             initiation of study treatment.&#xD;
&#xD;
             5. Patients who previously received organ transplantation or stem cell&#xD;
             transplantation.&#xD;
&#xD;
             6. Patients with clinically significant cardiovascular and cerebrovascular diseases.&#xD;
&#xD;
             7. Patients with dysphagia, active gastrointestinal diseases or other conditions that&#xD;
             will interfere significantly with the absorption, distribution, metabolism or&#xD;
             excretion of study medication.&#xD;
&#xD;
             8. Patients who are active carrier of hepatitis B (HBsAg positive and HBV-DNA&#xD;
             ≥500IU/mL), hepatitis C virus antibody, treponema pallidum antibody or HIV antibody.&#xD;
&#xD;
             9. Patients with interstitial lung disease history or signs of active interstitial&#xD;
             lung disease.&#xD;
&#xD;
             10. Pregnant and lactating women. 11. Patients with known allergy or delayed&#xD;
             hypersensitivity reaction to study drug or its excipients.&#xD;
&#xD;
             12. Patients who need to receive drugs which could induce QT/QTc interval prolongation&#xD;
             or torsade de pointes, or drugs which are potent CYP3A4 inhibitors or inducers within&#xD;
             last 14 days before the initiation of study treatment and during the study.&#xD;
&#xD;
             13. Patients who are currently under treatment of warfarin or other coumarin&#xD;
             anticoagulants.&#xD;
&#xD;
             14. 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>Jue Feng</last_name>
    <phone>021-64175590-88900</phone>
    <email>13788956275@163.com</email>
  </overall_contact>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 22, 2018</study_first_submitted>
  <study_first_submitted_qc>November 22, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>November 22, 2018</last_update_submitted>
  <last_update_submitted_qc>November 22, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 27, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fudan University</investigator_affiliation>
    <investigator_full_name>Chang Jian Hua</investigator_full_name>
    <investigator_title>Director</investigator_title>
  </responsible_party>
  <keyword>NSCLC</keyword>
  <keyword>Brain metastases</keyword>
  <keyword>ALK mutations</keyword>
  <keyword>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/NCT03753685
org study id: BTP-42324-IIT
nct id: NCT03753685
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: Duration of response based on intracranial response (iDOR) according to RECIST 1.1
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: 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: Duration of response based on overall response (DOR) according to RECIST 1.1
time frame: 36 months
description: Defined as time from documentation of overall response (CR or PR) to overall disease progression or death, 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) Capsule
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: Jue Feng
phone: 021-64175590-88900
email: 13788956275@163.com
responsible party type: Principal Investigator
investigator affiliation: Fudan University
investigator full name: Chang Jian Hua
investigator title: Director
mesh term: Neoplasm Metastasis
mesh term: Brain Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Ensartinib
sharing ipd: No