<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/NCT04507035</url>
  </required_header>
  <id_info>
    <org_study_id>head and neck cancer 007</org_study_id>
    <nct_id>NCT04507035</nct_id>
  </id_info>
  <brief_title>Treating Locally Advanced Head and Neck Malignant Tumor With Anlotinib and Chemoradiotherapy</brief_title>
  <official_title>Study on the Treatment of Refractory and Locally Advanced Head and Neck Malignant Tumor With Anlotinib Hydrochloride Capsules Combined With Chemoradiotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sun Yat-sen University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Head and neck tumors include well-differentiated squamous cell carcinoma, adenocarcinoma,&#xD;
      adenoid cystic carcinoma, small cell carcinoma, sarcoma, olfactory blastoma, and&#xD;
      mucoepidermoid carcinoma, which are highly invasive and have a high rate of recurrence and&#xD;
      metastasis. For tumors that cannot be radically removed at the local advanced stage, even&#xD;
      after traditional comprehensive treatment, survival is still very low. Therefore, we need to&#xD;
      explore new treatment methods to achieve tumor degeneration and increase the surgical&#xD;
      resection rate or control local lesions to improve the survival rate of tumors. According to&#xD;
      previous research reports and clinical exploration, anlotinib has evidence support for the&#xD;
      treatment of locally advanced head and neck tumors. With a considerable effect in the early&#xD;
      stage, we tried to initially observe the clinical treatment efficiency, toxic and side&#xD;
      effects, progression-free survival time, overall survival time and quality of life of&#xD;
      anlotinib in the treatment of patients with refractory head and neck carcinoma. Provide&#xD;
      patients with a more optimal treatment plan and improve survival.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      We will prospectively collect 30 patients who receive anlotinib combined with&#xD;
      chemoradiotherapy. Data will be stored in a private database. The process of data collection&#xD;
      will be supervised and regular data examination will be performed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">September 1, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2022</primary_completion_date>
  <phase>Phase 4</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>Anlotinib treatment plus chemoradiotherapy</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective response rate</measure>
    <time_frame>Three months</time_frame>
    <description>Complete response rate and partial response rate: measured according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 by means of computed tomography (CT) or magnetic resonance imaging (MRI) at each follow-up.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse events rate</measure>
    <time_frame>Three months</time_frame>
    <description>Adverse events during the treatment period using Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Two years</time_frame>
    <description>Defined as the time from randomization until disease progression or death from any cause, whichever happens first. Patients who withdraw or who are lost to follow-up will be censored at the date last known to be alive and progression free. Patients not having an event will be censored at the date last seen alive.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Two years</time_frame>
    <description>defined as the time from randomization until death from any cause. Patients who withdraw or who are lost to follow-up will be censored at the date last known to be alive. Patients remaining alive throughout the duration of the study will have their survival time censored on the date last seen alive.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Head and Neck Cancer</condition>
  <arm_group>
    <arm_group_label>Anlotinib group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After 2 cycles of anlotinib treatment, we evaluate the therapeutic effect of tumor treatment: If it achieve downgrading and is operable, surgical treatment will be performed; if it is still inoperable and could accept radiotherapy, radiotherapy and chemotherapy will be combined with oral chemotherapy of anlotinib until the end of radiotherapy. Efficiency and side effects will be evaluated within 3 months after therapy. Finally, the survival is in follow-up.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anlotinib hydrochloride capsules</intervention_name>
    <description>Using anlotinib of 2 cycles as the first-line therapy.</description>
    <arm_group_label>Anlotinib group</arm_group_label>
    <other_name>Fukewei, YBH00802018</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female, aged 18 to 75 years;&#xD;
&#xD;
          -  Performance status (PS) score ≤ 1 points;&#xD;
&#xD;
          -  The expected survival period is more than 3 months;&#xD;
&#xD;
          -  Highly differentiated squamous cell carcinoma or non-squamous cell carcinoma of the&#xD;
             head and neck diagnosed by pathology and/or cytology, including sarcoma, adenoid&#xD;
             cystic carcinoma, olfactory blastoma, mucoepidermoid carcinoma, etc.; those whose&#xD;
             primary tumor cannot be cured by surgery;&#xD;
&#xD;
          -  With measurable lesions: According to the evaluation criteria for the efficacy of&#xD;
             solid tumors (Response Evaluation Criteria In Solid Tumors 1.1), the patient has at&#xD;
             least one measurable lesion. The measurable lesion should not have received local&#xD;
             treatment such as radiotherapy (target lesion located in the previous radiotherapy&#xD;
             area, if it is confirmed that significant progress has occurred , And comply with&#xD;
             evaluation standard, can also be used as target lesions);&#xD;
&#xD;
          -  No previous anti-tumor therapy, including anti-angiogenesis therapy, such as&#xD;
             pazopanib, sunitinib, sorafenib, regorafenib, etc.;&#xD;
&#xD;
          -  Sufficient liver function: total bilirubin ≤ upper limit of normal value (ULN);&#xD;
             glutamic oxalacetic transaminase (AST) and glutamic-pyruvic transaminase (ALT) ≤ 2&#xD;
             times upper limit of normal value (ULN); alkaline phosphatase ≤ 5 times upper limit of&#xD;
             normal value (ULN);&#xD;
&#xD;
          -  Adequate renal function: creatinine clearance rate ≥80 mL/min;&#xD;
&#xD;
          -  Adequate blood function: absolute neutrophil count (ANC) ≥2×109/L, platelet count&#xD;
             ≥100×109/L and hemoglobin ≥9g/dL;&#xD;
&#xD;
          -  No serious heart, lung and other important organ dysfunction;&#xD;
&#xD;
          -  Women of childbearing age must have taken reliable contraceptive measures; pregnancy&#xD;
             tests (serum or urine) are negative within 7 days before enrollment, and must be&#xD;
             non-lactating patients; and are willing to adopt appropriate during the test and&#xD;
             within 6 months after the last treatment Methods of contraception. For men, it is&#xD;
             necessary to agree to use appropriate methods of contraception or surgical&#xD;
             sterilization during the trial and 8 weeks after the last dose;&#xD;
&#xD;
          -  The subjects voluntarily joined the study and signed an informed consent form with&#xD;
             good compliance and cooperated with the follow-up.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Can undergo radical surgery or cannot tolerate anti-tumor treatment;&#xD;
&#xD;
          -  Women who are pregnant or breastfeeding, have fertility but are unwilling or unable to&#xD;
             take effective contraceptive measures;&#xD;
&#xD;
          -  People with high blood pressure who cannot be well controlled by antihypertensive&#xD;
             drugs (systolic blood pressure&gt; 150 mmHg, diastolic blood pressure&gt; 100 mmHg);&#xD;
&#xD;
          -  Patients with clinically significant cardiovascular disease within 6 months before&#xD;
             enrollment, including uncontrolled hypertension, myocardial infarction, or unstable&#xD;
             angina; New York Heart Association (NYHA) congestive heart failure of grade II or&#xD;
             higher, severe Of arrhythmia requiring treatment (including QT interval ≥440 ms), or&#xD;
             cardiac ejection fraction &lt;50%, peripheral vascular disease of grade II or higher;&#xD;
&#xD;
          -  Abnormal blood coagulation function (INR&gt;1.5 or prothrombin time (PT)&gt;ULN+4 seconds or&#xD;
             activated partial thromboplastin time (APTT) &gt;1.5 ULN), have bleeding tendency or are&#xD;
             undergoing thrombolysis or anticoagulation treatment;&#xD;
&#xD;
          -  There was obvious hemoptysis blood 2 months before enrollment, or the daily hemoptysis&#xD;
             amount was 2.5ml or more;&#xD;
&#xD;
          -  Significant clinically significant bleeding symptoms or clear bleeding tendency, such&#xD;
             as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline occult blood ++ and&#xD;
             above, or suffering from vasculitis within 3 months before enrollment; Known&#xD;
             hereditary or acquired bleeding and thrombotic tendency;&#xD;
&#xD;
          -  Arterial/venous thromboembolic events within 12 months before enrollment;&#xD;
&#xD;
          -  Have undergone major surgery within 4 weeks of enrollment or accompanied by severe,&#xD;
             non-healing wounds, ulcers or fractures;&#xD;
&#xD;
          -  There are obvious factors that affect the absorption of oral drugs;&#xD;
&#xD;
          -  Abdominal fistula, gastrointestinal perforation or abdominal abscess occurred 6 months&#xD;
             before enrollment;&#xD;
&#xD;
          -  Urinary routines suggest that urine protein is ≥++, and that the amount of urine&#xD;
             protein in 24 hours is ≥1.0g;&#xD;
&#xD;
          -  Serous cavity fluid accumulation with clinical symptoms and requiring symptomatic&#xD;
             treatment;&#xD;
&#xD;
          -  Active infections require antimicrobial treatment;&#xD;
&#xD;
          -  Have a history of central nervous system diseases, including primary brain tumors,&#xD;
             seizures without standard medication, any brain metastases or have cerebrovascular&#xD;
             accidents (CVA, stroke), transient ischemic attack (TIA), or 6 A history of&#xD;
             subarachnoid hemorrhage within the month;&#xD;
&#xD;
          -  Participated in clinical trials of other drugs 4 weeks before enrollment;&#xD;
&#xD;
          -  Other malignant tumors in the past or at the same time (except for malignant tumors&#xD;
             that have been cured and survived for more than 5 years without cancer, such as basal&#xD;
             cell carcinoma of the skin, carcinoma in situ of the cervix, and papillary thyroid&#xD;
             carcinoma, etc.);&#xD;
&#xD;
          -  Those who have received VEGFR inhibitors, such as pazopanib, sunitinib, sorafenib,&#xD;
             regorafenib, etc.;&#xD;
&#xD;
          -  Those who are known to have a history of psychotropic substance abuse, alcoholism or&#xD;
             drug use and are unable to quit or have mental disorders;&#xD;
&#xD;
          -  The investigator judges other conditions that may affect the progress of the clinical&#xD;
             study and the judgment of the research results.&#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>Yong Chen, M.D.</last_name>
    <role>Study Chair</role>
    <affiliation>First Affiliated Hospital, Sun Yat-Sen University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Zhen-wei Peng, Ph.D.</last_name>
    <phone>008687755766</phone>
    <phone_ext>8576</phone_ext>
    <email>pzhenw@mail.sysu.edu.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>The First Affiliated Hospital of Sun Yat-sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510080</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yong Chen</last_name>
      <phone>8602087338692</phone>
      <email>chenyong@mail.sysu.edu.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>July 17, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2020</study_first_posted>
  <last_update_submitted>August 27, 2020</last_update_submitted>
  <last_update_submitted_qc>August 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Zhen-Wei Peng</investigator_full_name>
    <investigator_title>Clinical professor. Zhen-Wei Peng</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Head and Neck Neoplasms</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <!-- 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/NCT04507035
org study id: head and neck cancer 007
nct id: NCT04507035
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
Head and neck tumors include well-differentiated squamous cell carcinoma, adenocarcinoma,
      adenoid cystic carcinoma, small cell carcinoma, sarcoma, olfactory blastoma, and
      mucoepidermoid carcinoma, which are highly invasive and have a high rate of recurrence and
      metastasis. For tumors that cannot be radically removed at the local advanced stage, even
      after traditional comprehensive treatment, survival is still very low. Therefore, we need to
      explore new treatment methods to achieve tumor degeneration and increase the surgical
      resection rate or control local lesions to improve the survival rate of tumors. According to
      previous research reports and clinical exploration, anlotinib has evidence support for the
      treatment of locally advanced head and neck tumors. With a considerable effect in the early
      stage, we tried to initially observe the clinical treatment efficiency, toxic and side
      effects, progression-free survival time, overall survival time and quality of life of
      anlotinib in the treatment of patients with refractory head and neck carcinoma. Provide
      patients with a more optimal treatment plan and improve survival.
We will prospectively collect 30 patients who receive anlotinib combined with
      chemoradiotherapy. Data will be stored in a private database. The process of data collection
      will be supervised and regular data examination will be performed.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Anlotinib treatment plus chemoradiotherapy
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate
time frame: Three months
description: Complete response rate and partial response rate: measured according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 by means of computed tomography (CT) or magnetic resonance imaging (MRI) at each follow-up.
measure: Adverse events rate
time frame: Three months
description: Adverse events during the treatment period using Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0).
measure: Progression-free survival (PFS)
time frame: Two years
description: Defined as the time from randomization until disease progression or death from any cause, whichever happens first. Patients who withdraw or who are lost to follow-up will be censored at the date last known to be alive and progression free. Patients not having an event will be censored at the date last seen alive.
measure: Overall survival (OS)
time frame: Two years
description: defined as the time from randomization until death from any cause. Patients who withdraw or who are lost to follow-up will be censored at the date last known to be alive. Patients remaining alive throughout the duration of the study will have their survival time censored on the date last seen alive.
arm group label: Anlotinib group
arm group type: Experimental
description: After 2 cycles of anlotinib treatment, we evaluate the therapeutic effect of tumor treatment: If it achieve downgrading and is operable, surgical treatment will be performed; if it is still inoperable and could accept radiotherapy, radiotherapy and chemotherapy will be combined with oral chemotherapy of anlotinib until the end of radiotherapy. Efficiency and side effects will be evaluated within 3 months after therapy. Finally, the survival is in follow-up.
intervention type: Drug
intervention name: Anlotinib hydrochloride capsules
description: Using anlotinib of 2 cycles as the first-line therapy.
arm group label: Anlotinib group
other name: Fukewei, YBH00802018
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Yong Chen, M.D.
role: Study Chair
affiliation: First Affiliated Hospital, Sun Yat-Sen University
last name: Zhen-wei Peng, Ph.D.
phone: 008687755766
phone ext: 8576
email: pzhenw@mail.sysu.edu.cn
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Zhen-Wei Peng
investigator title: Clinical professor. Zhen-Wei Peng
mesh term: Head and Neck Neoplasms
mesh term: Neoplasms