<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/NCT02989259</url>
  </required_header>
  <id_info>
    <org_study_id>CH-H&amp;N-008-1</org_study_id>
    <nct_id>NCT02989259</nct_id>
  </id_info>
  <brief_title>Apatinib for Advanced Non-squamous Head and Neck Cancer</brief_title>
  <official_title>The Clinical Study of Apatinib for Patients With Advanced Non-squamous Head and Neck Cancer</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>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this study, the investigators try to evaluate the efficacy and safety of apatinib in&#xD;
      advanced non-squamous head and neck cancer and to validate the correlative biomarkers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There is no standard therapy for patients with advanced (unresectable, locally advanced,&#xD;
      recurrent or metastatic) non-squamous head and neck cancer. Apatinib is a novel vascular&#xD;
      endothelial growth factor receptor 2 tyrosine kinase inhibitor, which has been approved for&#xD;
      the treatment of patients with advanced gastric cancer refractory to two or more lines of&#xD;
      prior chemotherapy. Vascular endothelial growth factor is highly expressed in non-squamous&#xD;
      head and neck cancer and its expression correlates with stage, tumour size, vascular&#xD;
      invasion, recurrence and metastasis. In this study, the investigators try to evaluate the&#xD;
      efficacy and safety of apatinib in advanced non-squamous head and neck cancer and to validate&#xD;
      the correlative biomarkers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>December 2016</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2018</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>Response Rate</measure>
    <time_frame>up to 3 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>up to 3 years</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Overall survival</measure>
    <time_frame>up to 3 years</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>up to 3 years</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>serum soluble VEGFR2</measure>
    <time_frame>baseline</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>tumor phosphorylated VEGFR2 (p-VEGFR2) expressions</measure>
    <time_frame>baseline</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Head and Neck Neoplasms</condition>
  <arm_group>
    <arm_group_label>apatinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>apatinib 500mg p.o. qd</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib</intervention_name>
    <description>apatinib 500mg p.o. qd</description>
    <arm_group_label>apatinib</arm_group_label>
    <other_name>ApatinibMesylate tablet</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 years to 75 years;&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2;&#xD;
&#xD;
          -  Life expectancy of more than 12 weeks;&#xD;
&#xD;
          -  At least one measurable lesion according to RECIST 1.1 which has not received&#xD;
             radiotherapy =&lt; 3 months;&#xD;
&#xD;
          -  Histologically confirmed advanced (unresectable, locally advanced, recurrent or&#xD;
             metastatic) non-squamous head and neck cancer, including adenocarcinoma,&#xD;
             mucoepidermoid carcinoma, acinar cell carcinoma and adenoid cystic carcinoma;&#xD;
&#xD;
          -  Recurrent and or metastatic lesions which are not suitable for local treatment;&#xD;
&#xD;
          -  For patients with mucoepidermoid carcinoma, acinar cell carcinoma or adenoid cystic&#xD;
             carcinoma, metastatic disease documented as having shown progression on a scan (CT,&#xD;
             MRI) compared to a previous scan taken at any time in the past 12 months;&#xD;
&#xD;
          -  For patients with adenocarcinoma, one regimen of prior chemotherapy was received for&#xD;
             recurrent and or metastatic diseases;&#xD;
&#xD;
          -  Adequate hepatic, renal, heart, and hematologic functions: absolute neutrophil count&#xD;
             (ANC) ≥ 1.5×109/L, platelet count (PLT) ≥ 100×109/L, hemoglobin (HB) ≥ 90 g/L, total&#xD;
             bilirubin (TBIL) ≤ 1.5×upper limit of normal (ULN), alternate aminotransferase (ALT)&#xD;
             or aspartate aminotransferase (AST) ≤ 2.5×ULN (or ≤ 5×ULN in patients with liver&#xD;
             metastases), Serum Cr ≤ 1×ULN, Cr clearance ≥ 50 mL/min, international normalized&#xD;
             ratio (INR) &lt; 1.5 or PT &lt; ULN+4s or activated partial thromboplastin time (APTT) &lt;&#xD;
             1.5×ULN, proteinuria &lt; (++) or urinary protein ≤ 1.0 g/24 hrs;&#xD;
&#xD;
          -  For women of child-bearing age, the pregnancy test results (serum or urine) within 7&#xD;
             days before enrolment must be negative. They will take appropriate methods for&#xD;
             contraception during the study until the 8th week post the last administration of&#xD;
             study drug. For men (previous surgical sterilization accepted), will take appropriate&#xD;
             methods for contraception during the study until the 8th week post the last&#xD;
             administration of study drug.&#xD;
&#xD;
          -  Signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Accumulation of coelomic fluid (e.g. pleural effusion, ascites fluid, cardiac&#xD;
             effusion) requiring treatment;&#xD;
&#xD;
          -  Other malignancy within the past five years other than basal cell skin cancer, or&#xD;
             carcinoma in situ of the cervix;&#xD;
&#xD;
          -  Factors affecting the oral medication (e.g. inability to swallow, chronic diarrhea and&#xD;
             intestinal obstruction);&#xD;
&#xD;
          -  Major injuries and/or surgery =&lt; 4 weeks prior to registration with incomplete wound&#xD;
             healing. Patients who have received radiotherapy (except local palliative&#xD;
             radiotherapy), chemotherapy, molecular targeted therapy =&lt; 3 weeks, or&#xD;
             nitrosoureas/mitomycin chemotherapy =&lt; 6 weeks prior to registration;&#xD;
&#xD;
          -  Patients with poor-controlled arterial hypertension (systolic pressure ≥ 140 mmHg&#xD;
             and/or diastolic pressure ≥ 90 mm Hg) despite standard medical management;&#xD;
&#xD;
          -  Suffered from grade II or above myocardial ischemia or myocardial infarction,&#xD;
             uncontrolled arrhythmias (including QT interval male ≥ 450 ms, female ≥ 470 ms). Grade&#xD;
             III-IV cardiac insufficiency according to New York Heart Association (NYHA) criteria&#xD;
             or echocardiography check: left ventricular ejection fraction (LVEF)&lt;50%;&#xD;
&#xD;
          -  History of clinically significant haemoptysis =&lt; 2 months (more than half of one tea&#xD;
             spoon of fresh blood per day) prior to registration. Coagulation disfunction,&#xD;
             hemorrhagic tendency or receiving anticoagulant therapy;&#xD;
&#xD;
          -  History of clinically relevant major bleeding event (e.g. gastrointestinal hemorrhage,&#xD;
             bleeding ulcer, occult blood ≥ (++), and vasculitis) =&lt; 3 months prior to&#xD;
             randomization;&#xD;
&#xD;
          -  Patients who have active brain metastases or leptomeningeal disease. Patients with&#xD;
             treated brain metastases are eligible if they are clinically stable with regard to&#xD;
             neurologic function, off steroids after cranial irradiation ending at least 3 weeks&#xD;
             prior to randomization, or after surgical resection performed at least 3 weeks prior&#xD;
             to randomization. No evidence of Grade greater than or equal to 1 central nervous&#xD;
             system (CNS) hemorrhage based on pretreatment CT or MRI scan;&#xD;
&#xD;
          -  Centrally located tumors of local invasion of major blood vessels, or distinct&#xD;
             interstitial lung disease by the chest radiographic findings (CT or MRI);&#xD;
&#xD;
          -  Treatment with other investigational drugs or other anti-cancer therapy;&#xD;
&#xD;
          -  Previous therapy with other VEGFR inhibitors (other than bevacizumab);&#xD;
&#xD;
          -  Treatment in another investigational trial =&lt; 4 weeks prior to registration;&#xD;
&#xD;
          -  History of hypersensitivity to apatinib and/or the excipients of the trial drugs;&#xD;
&#xD;
          -  Active or chronic hepatitis C and/or B infection, or other active uncontrolled&#xD;
             infection;&#xD;
&#xD;
          -  History of immunodeficiency disease (including HIV positive), concurrent acquired or&#xD;
             congenital immunodeficiency syndrome, or history of organ transplantation;&#xD;
&#xD;
          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess&#xD;
             =&lt; 6 months prior to registration;&#xD;
&#xD;
          -  History of arterial or venous thromboembolic events (e.g. cerebrovascular accident,&#xD;
             cardiovascular accident, deep venous thrombosis and pulmonary embolism) =&lt; 12 months&#xD;
             prior to randomization;&#xD;
&#xD;
          -  Administration of strong/potent cytochrome P450 (CYP)3A4 inhibitors within 7 days, or&#xD;
             inducers within 12 days;&#xD;
&#xD;
          -  Evidence of significant medical illness that in the investigator's judgment will&#xD;
             substantially increase the risk associated with the subject's participation in and&#xD;
             completion of the study;&#xD;
&#xD;
          -  History of mental diseases;&#xD;
&#xD;
          -  Other conditions regimented at investigators' discretion.&#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_official>
    <last_name>Xiaohui He, B.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) &amp; Peking Union Medical College (PUMC)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Xiaohui He, B.D.</last_name>
    <phone>+86-13810670129</phone>
    <email>xiaohuih2008@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lin Gui, M.D.</last_name>
    <phone>+86-13520372817</phone>
    <email>guilindoctor@126.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) &amp; Peking Union Medical College (PUMC)</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100021</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xiaohui He, B.D.</last_name>
      <phone>+86-13810670129</phone>
      <email>xiaohuih2008@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Lin Gui, M.D.</last_name>
      <phone>+86-13520372817</phone>
      <email>guilindoctor@126.com</email>
    </contact_backup>
    <investigator>
      <last_name>Xiaohui He, B.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Lin Gui, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <results_reference>
    <citation>Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, Liu W, Tong J, Liu Y, Xu R, Wang Z, Wang Q, Ouyang X, Yang Y, Ba Y, Liang J, Lin X, Luo D, Zheng R, Wang X, Sun G, Wang L, Zheng L, Guo H, Wu J, Xu N, Yang J, Zhang H, Cheng Y, Wang N, Chen L, Fan Z, Sun P, Yu H. Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction. J Clin Oncol. 2016 May 1;34(13):1448-54. doi: 10.1200/JCO.2015.63.5995. Epub 2016 Feb 16.</citation>
    <PMID>26884585</PMID>
  </results_reference>
  <results_reference>
    <citation>Le Tourneau C, Razak AR, Levy C, Calugaru V, Galatoire O, Dendale R, Desjardins L, Gan HK. Role of chemotherapy and molecularly targeted agents in the treatment of adenoid cystic carcinoma of the lacrimal gland. Br J Ophthalmol. 2011 Nov;95(11):1483-9. doi: 10.1136/bjo.2010.192351. Epub 2010 Dec 22.</citation>
    <PMID>21183517</PMID>
  </results_reference>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>December 8, 2016</study_first_submitted>
  <study_first_submitted_qc>December 8, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 12, 2016</study_first_posted>
  <last_update_submitted>December 11, 2016</last_update_submitted>
  <last_update_submitted_qc>December 11, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 13, 2016</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>Xiaohui He</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>apatinib</keyword>
  <keyword>advanced head and neck cancer</keyword>
  <keyword>non-squamous</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Head and Neck Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apatinib</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/NCT02989259
org study id: CH-H&N-008-1
nct id: NCT02989259
lead sponsor: 
has dmc: Yes
In this study, the investigators try to evaluate the efficacy and safety of apatinib in
      advanced non-squamous head and neck cancer and to validate the correlative biomarkers.
There is no standard therapy for patients with advanced (unresectable, locally advanced,
      recurrent or metastatic) non-squamous head and neck cancer. Apatinib is a novel vascular
      endothelial growth factor receptor 2 tyrosine kinase inhibitor, which has been approved for
      the treatment of patients with advanced gastric cancer refractory to two or more lines of
      prior chemotherapy. Vascular endothelial growth factor is highly expressed in non-squamous
      head and neck cancer and its expression correlates with stage, tumour size, vascular
      invasion, recurrence and metastasis. In this study, the investigators try to evaluate the
      efficacy and safety of apatinib in advanced non-squamous head and neck cancer and to validate
      the correlative biomarkers.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Response Rate
time frame: up to 3 years
measure: Progression-free survival
time frame: up to 3 years
measure: Overall survival
time frame: up to 3 years
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: up to 3 years
measure: serum soluble VEGFR2
time frame: baseline
measure: tumor phosphorylated VEGFR2 (p-VEGFR2) expressions
time frame: baseline
arm group label: apatinib
arm group type: Experimental
description: apatinib 500mg p.o. qd
intervention type: Drug
intervention name: Apatinib
description: apatinib 500mg p.o. qd
arm group label: apatinib
other name: ApatinibMesylate tablet
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Xiaohui He, B.D.
role: Principal Investigator
affiliation: Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC)
last name: Xiaohui He, B.D.
phone: +86-13810670129
email: xiaohuih2008@163.com
last name: Lin Gui, M.D.
phone: +86-13520372817
email: guilindoctor@126.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: China
citation: Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, Liu W, Tong J, Liu Y, Xu R, Wang Z, Wang Q, Ouyang X, Yang Y, Ba Y, Liang J, Lin X, Luo D, Zheng R, Wang X, Sun G, Wang L, Zheng L, Guo H, Wu J, Xu N, Yang J, Zhang H, Cheng Y, Wang N, Chen L, Fan Z, Sun P, Yu H. Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction. J Clin Oncol. 2016 May 1;34(13):1448-54. doi: 10.1200/JCO.2015.63.5995. Epub 2016 Feb 16.
PMID: 26884585
citation: Le Tourneau C, Razak AR, Levy C, Calugaru V, Galatoire O, Dendale R, Desjardins L, Gan HK. Role of chemotherapy and molecularly targeted agents in the treatment of adenoid cystic carcinoma of the lacrimal gland. Br J Ophthalmol. 2011 Nov;95(11):1483-9. doi: 10.1136/bjo.2010.192351. Epub 2010 Dec 22.
PMID: 21183517
responsible party type: Principal Investigator
investigator affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
investigator full name: Xiaohui He
investigator title: Professor
mesh term: Head and Neck Neoplasms
mesh term: Apatinib
sharing ipd: No