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/NCT06038461</url>
    </required_header>
    <id_info>
      <org_study_id>HMPL-012-SPRING-NEN106</org_study_id>
      <nct_id>NCT06038461</nct_id>
    </id_info>
    <brief_title>An Open, Single-center Clinical Study of Surufatinib Combined With Temozolomide and S-1 in the First-line Treatment of Advanced Neuroendocrine Tumors</brief_title>
    <official_title>An Open, Single-center Clinical Study of Surufatinib Combined With Temozolomide and S-1 in the First-line Treatment of Advanced Neuroendocrine Tumors</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</source>
    <oversight_info>
      <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 prospective, open, single-center study evaluating the efficacy and safety of&#xD;
        surufatinib Combined With Temozolomide and S-1 as the first-line treatment of advanced&#xD;
        neuroendocrine tumors&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 15, 2023</start_date>
    <completion_date type="Anticipated">September 15, 2026</completion_date>
    <primary_completion_date type="Anticipated">September 15, 2026</primary_completion_date>
    <phase>Phase 1/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>
      <intervention_model_description>Surufatinib Combined With Temozolomide and S-1</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Objective response rate (ORR)</measure>
      <time_frame>approximately 1 years</time_frame>
      <description>the proportion of patients with complete response or partial response, using RESIST v1.1</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Progression-Free Survival (PFS)</measure>
      <time_frame>approximately 1 years</time_frame>
      <description>time from first-dose to the first documented disease progression or death</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease Control Rate (DCR)</measure>
      <time_frame>approximately 1 years</time_frame>
      <description>the proportion of patients with complete response, partial response or stable disease, using RESIST v1.1</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Neuroendocrine Tumors</condition>
    <arm_group>
      <arm_group_label>Surufatinib Combined With Temozolomide and S-1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients will receive surufatinib combined with temozolomide and S-1 once every three weeks as the second-line treatment until disease progression or intolerable toxicity or patients withdrawal of consent.&#xD;
  Phase I: DLTs of surufatinib combined with temozolomide and S-1 will be evaluated based on NCI CTCAE v 5.0 in the first cycle.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Surufatinib Combined With Temozolomide and S-1</intervention_name>
      <description>Phase I:&#xD;
  Surufatinib: 250mg, QD, PO, Q3W; Temozolomide: 200-300mg, d10-d14, QD, PO, Q3W; S-1: 40-60mg, d1-d14, BID, PO, Q3W.&#xD;
  Phase II:&#xD;
  Surufatinib, Temozolomide and S-1：RP2D</description>
      <arm_group_label>Surufatinib Combined With Temozolomide and S-1</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Aged 18-75years (inclusive);&#xD;
  &#xD;
            -  Histopathologically confirmed diagnosis of advanced MGMT0/1+ (G1, G2 or G3)&#xD;
               neuroendocrine tumor (locally advanced, unresectable or distant metastasis);&#xD;
  &#xD;
            -  Previously untreated with systemic therapy;&#xD;
  &#xD;
            -  Have at least one measurable lesion according to RECIST v1.1;&#xD;
  &#xD;
            -  ECOG performance status: 0-2(determined by investigator);&#xD;
  &#xD;
            -  Expected survival time &gt; 3 months;&#xD;
  &#xD;
            -  Adequate hepatic, renal, heart, and hematologic functions;&#xD;
  &#xD;
            -  Urine protein &lt; ++ . If Urine protein ≥ ++ ,the amount of urine protein in 24 hours&#xD;
               ≤1.0g;&#xD;
  &#xD;
            -  Before the first dose, serum HCG examination of potential childbearing-women must be&#xD;
               negative; Men/Women of childbearing potential must agree to use a highly effective&#xD;
               contraceptive method (such as double barrier contraceptive method, condom, oral or&#xD;
               injectable contraceptives and intrauterine device) throughout treatment and for at&#xD;
               least 90 days after study completion.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Neuroendocrine cancer, adenocarcinoid, goblet cell carcinoid,&#xD;
  &#xD;
            -  Functional NETs which need to control symptoms by long-acting somatostatin analogues;&#xD;
  &#xD;
            -  Received a major surgery which requires at least 3 weeks after recovery time, to&#xD;
               undergo surgery on treatment of this research within 4 weeks prior to treatment;&#xD;
  &#xD;
            -  Have uncontrolled hypertension, defined as systolic blood pressure &gt;140 mmHg or&#xD;
               diastolic blood pressure &gt;90 mm Hg, while under anti-hypertension treatment;&#xD;
  &#xD;
            -  Patients with active ulcer, intestinal perforation and intestinal obstruction;&#xD;
  &#xD;
            -  With active bleeding or bleeding tendency;&#xD;
  &#xD;
            -  Severe history of cardiovascular and cerebrovascular diseases;&#xD;
  &#xD;
            -  Other malignancies diagnosed within the previous 5 years, except basal cell carcinoma&#xD;
               or cervical carcinoma in situ after radical resection.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Yihebali Chi, PhD</last_name>
      <phone>010-67781331</phone>
      <email>yihebalichi@hotmail.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</name>
        <address>
          <city>Beijing</city>
          <state>Beijing</state>
          <zip>100021</zip>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Yihebali Chi, doctor</last_name>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 8, 2023</study_first_submitted>
    <study_first_submitted_qc>September 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 14, 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 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</investigator_affiliation>
      <investigator_full_name>YILIBAHE CHI</investigator_full_name>
      <investigator_title>Professor, Department of Medical Oncology</investigator_title>
    </responsible_party>
    <keyword>Surufatinib</keyword>
    <keyword>Temozolomide and S-1</keyword>
    <keyword>First-line treatment</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neuroendocrine Tumors</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Temozolomide</mesh_term>
    </intervention_browse>
    <!-- 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/NCT06038461
  org study id: HMPL-012-SPRING-NEN106
  nct id: NCT06038461
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  This is a prospective, open, single-center study evaluating the efficacy and safety of
        surufatinib Combined With Temozolomide and S-1 as the first-line treatment of advanced
        neuroendocrine tumors
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: Surufatinib Combined With Temozolomide and S-1
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Objective response rate (ORR)
  time frame: approximately 1 years
  description: the proportion of patients with complete response or partial response, using RESIST v1.1
  measure: Progression-Free Survival (PFS)
  time frame: approximately 1 years
  description: time from first-dose to the first documented disease progression or death
  measure: Disease Control Rate (DCR)
  time frame: approximately 1 years
  description: the proportion of patients with complete response, partial response or stable disease, using RESIST v1.1
  arm group label: Surufatinib Combined With Temozolomide and S-1
  arm group type: Experimental
  description: Patients will receive surufatinib combined with temozolomide and S-1 once every three weeks as the second-line treatment until disease progression or intolerable toxicity or patients withdrawal of consent.
  Phase I: DLTs of surufatinib combined with temozolomide and S-1 will be evaluated based on NCI CTCAE v 5.0 in the first cycle.
  intervention type: Drug
  intervention name: Surufatinib Combined With Temozolomide and S-1
  description: Phase I:
  Surufatinib: 250mg, QD, PO, Q3W; Temozolomide: 200-300mg, d10-d14, QD, PO, Q3W; S-1: 40-60mg, d1-d14, BID, PO, Q3W.
  Phase II:
  Surufatinib, Temozolomide and S-1：RP2D
  arm group label: Surufatinib Combined With Temozolomide and S-1
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Yihebali Chi, PhD
  phone: 010-67781331
  email: yihebalichi@hotmail.com
  facility: 
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
  investigator full name: YILIBAHE CHI
  investigator title: Professor, Department of Medical Oncology
  mesh term: Neuroendocrine Tumors
  mesh term: Temozolomide