<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/NCT04501705</url>
  </required_header>
  <id_info>
    <org_study_id>OBU-BJ-CM-Ⅱ-008</org_study_id>
    <nct_id>NCT04501705</nct_id>
  </id_info>
  <brief_title>Apatinib in the Treatment of Recurrent Atypical/Malignant Meningioma in Adults</brief_title>
  <official_title>Clinical Study of Apatinib in the Treatment of Recurrent Atypical/Malignant Meningioma in Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beijing Sanbo Brain Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Beijing Sanbo Brain Hospital</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>
      Apatinib mesylate may be an effective treatment for recurrent atypical/malignant meningioma.&#xD;
      This prospective clinical study is now planned to verify the effectiveness and safety of&#xD;
      apatinib mesylate in the treatment of relapsed atypical/malignant meningioma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Vascular endothelial growth factor VEGF is related to the abnormal angiogenesis of meningioma&#xD;
      and can also activate other growth factor pathways. Meningiomas are vascular tumors. Studies&#xD;
      have shown that the expression of VEGF in atypical meningiomas is twice that of benign&#xD;
      meningiomas, and VEGF in anaplastic meningiomas is 10 times that of benign meningiomas.&#xD;
      Therefore, anti-angiogenesis therapy may be more effective for higher grade meningiomas.&#xD;
      Previous clinical studies have confirmed that anti-angiogenic drugs such as bevacizumab,&#xD;
      sunitinib and PTK 787 can slow down tumor growth and prolong progression-free survival for&#xD;
      recurrent atypical/malignant meningioma. In summary, apatinib mesylate may be an effective&#xD;
      treatment for recurrent atypical/malignant meningioma. This prospective clinical study is now&#xD;
      planned to verify the effectiveness and safety of apatinib mesylate in the treatment of&#xD;
      relapsed atypical/malignant meningioma.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 18, 2020</start_date>
  <completion_date type="Anticipated">August 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2025</primary_completion_date>
  <phase>N/A</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>PFS-6 %</measure>
    <time_frame>6-month progression-free survival</time_frame>
    <description>6-month progression-free survival</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ORR</measure>
    <time_frame>up to 5 years</time_frame>
    <description>Objective Response Rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OS</measure>
    <time_frame>up to 5 years</time_frame>
    <description>Overall survival</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">29</enrollment>
  <condition>Recurrent Atypical/Malignant Meningioma</condition>
  <arm_group>
    <arm_group_label>test group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib Mesylate</intervention_name>
    <description>Apatinib mesylate tablets: Orally, 500 mg, once a day, with warm water for half an hour after a meal (the time of taking the medicine every day should be the same as possible).&#xD;
Continue to use 28 days as a cycle, medication until disease progression (PD), intolerable toxicity occurs or the patient withdraws informed consent. However, the longest period does not exceed 24 cycles, and the treatment after 24 cycles is determined by the investigator.</description>
    <arm_group_label>test group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥18 years old (at the time of enrollment), regardless of gender.&#xD;
&#xD;
          2. The pathological diagnosis of atypical/malignant meningioma was clear after biopsy or&#xD;
             surgery.&#xD;
&#xD;
          3. The tumor recurrence is confirmed by MRI, that is, the diameter of the lesion on the&#xD;
             enhanced MRI image is ≥1cm, and ≥2 slices (slice interval 5mm) are visible; or after&#xD;
             another biopsy or surgery, the pathological diagnosis is atypical/malignant&#xD;
             meningioma.&#xD;
&#xD;
          4. Previous surgery and radiotherapy (including conventional radiotherapy or stereotactic&#xD;
             radiosurgery treatment) are required. There are no restrictions on whether to receive&#xD;
             chemotherapy or the number of times of the above treatments&#xD;
&#xD;
          5. The time interval from the last radiotherapy is ≥4 weeks.&#xD;
&#xD;
          6. The time interval from the last chemotherapy is ≥4 weeks, and the patients have fully&#xD;
             recovered from the acute toxicity of the last treatment.&#xD;
&#xD;
          7. The interval between the last biopsy or surgery is ≥2 weeks.&#xD;
&#xD;
          8. KPS score ≥50 points.&#xD;
&#xD;
          9. If the patient is on glucocorticoid therapy, the hormone dosage has stabilized or&#xD;
             decreased for at least 2 weeks before the baseline MRI.&#xD;
&#xD;
         10. The expected survival time is ≥12 weeks.&#xD;
&#xD;
         11. The main organ functions are normal, and there is no serious blood, heart, lung,&#xD;
             liver, kidney dysfunction and immune deficiency diseases. The laboratory inspection&#xD;
             meets the following requirements:&#xD;
&#xD;
        (1) Routine blood examination, which must be met (no blood transfusion within 14 days):&#xD;
&#xD;
          1. HGB≥100g/L;&#xD;
&#xD;
          2. WBC≥3.0×109/L; NEUT≥1.5×109/L;&#xD;
&#xD;
          3. PLT ≥100×109/L; (2) The biochemical inspection shall meet the following standards:&#xD;
&#xD;
        a. BIL≤1.5 times the upper limit of normal (ULN); b. ALT and AST≤2.0×ULN; c. Serum&#xD;
        Cr≤1.5×ULN or endogenous creatinine clearance ≥50ml/min (Cockcroft-Gault formula); (3)&#xD;
        Occult blood in stool (-); (4) Urine routine is normal, or urine protein &lt;(++), or 24-hour&#xD;
        urine protein &lt;1.0 g; (5) Left ventricular ejection fraction (LVEF) ≥50%. 12. The&#xD;
        coagulation function is normal, without active bleeding and thrombosis.&#xD;
&#xD;
          1. International standardized ratio INR≤1.5×ULN;&#xD;
&#xD;
          2. Partial thromboplastin time APTT≤1.5×ULN;&#xD;
&#xD;
          3. Prothrombin time PT≤1.5ULN. 13. Female patients of childbearing age must undergo a&#xD;
             negative pregnancy test (serum or urine) within 7 days before enrollment, and&#xD;
             voluntarily use appropriate methods of contraception during the observation period and&#xD;
             within 8 weeks after the last administration of apatinib mesylate tablets ; Male&#xD;
             patients of childbearing age should agree to use appropriate methods of contraception&#xD;
             during the observation period and within 8 weeks after the last administration of&#xD;
             apatinib mesylate tablets.&#xD;
&#xD;
             14. Patients need to provide 25-30 pieces of tumor tissue slices after the last biopsy&#xD;
             or surgery.&#xD;
&#xD;
             15. The patient has normal swallowing function and can swallow the tablet intact.&#xD;
&#xD;
             16. The patient voluntarily joined the study and signed an informed consent form&#xD;
             (ICF).&#xD;
&#xD;
             17. The patient is expected to have good compliance and be able to follow up the&#xD;
             efficacy and adverse reactions as required by the protocol.&#xD;
&#xD;
             Exclusion Criteria:&#xD;
&#xD;
               1. Past application of anti-tumor angiogenesis drugs;&#xD;
&#xD;
               2. Patients diagnosed with neurofibromatosis type 2 and other tumor syndromes;&#xD;
&#xD;
               3. People who are known to be allergic to any component of apatinib mesylate;&#xD;
&#xD;
               4. Antiepileptic drugs that induce liver enzymes are being used, unless&#xD;
                  antiepileptic drugs that have been replaced with non-hepatic enzymes are at least&#xD;
                  2 weeks away from enrollment;&#xD;
&#xD;
               5. Patients with other malignant tumors, unless they have survived for 5 years and&#xD;
                  the investigator believes that the risk of recurrence is low or patients with&#xD;
                  carcinoma in situ;&#xD;
&#xD;
               6. Patients with hypertension who cannot be reduced to the normal range after&#xD;
                  treatment with antihypertensive drugs (systolic blood pressure ≤ 140 mmHg /&#xD;
                  diastolic blood pressure ≤ 90 mmHg);&#xD;
&#xD;
               7. Patients with coronary heart disease ≥2 grade, arrhythmia (including QTc&#xD;
                  prolongation in men&gt;450 ms, women&gt;470 ms) and cardiac insufficiency;&#xD;
&#xD;
               8. Urine routine test indicates urine protein ≥(++), or 24-hour urine protein ≥1.0g;&#xD;
&#xD;
               9. Abnormal coagulation function (INR&gt;1.5 or prothrombin time (PT)&gt;ULN+4 seconds or&#xD;
                  APTT&gt;1.5×ULN), have bleeding tendency or are receiving thrombolytic or&#xD;
                  anticoagulant therapy;&#xD;
&#xD;
              10. There are many factors that affect the absorption of oral drugs, such as&#xD;
                  uncontrollable nausea and vomiting, chronic diarrhea and intestinal obstruction;&#xD;
&#xD;
              11. There is an infection that is difficult to control;&#xD;
&#xD;
              12. Those who had significant blood coughing up 2 months before enrollment, or had&#xD;
                  blood volume of 2.5ml or more per day; had clinically significant bleeding&#xD;
                  symptoms or had clear bleeding tendency within 3 months before enrollment, such&#xD;
                  as Gastrointestinal bleeding, hemorrhagic gastric ulcer, gastrointestinal&#xD;
                  perforation, stool occult blood++ and above at baseline, intratumoral or&#xD;
                  intracranial hemorrhage, or vasculitis, etc.;&#xD;
&#xD;
              13. Arterial/venous thrombosis events that occurred within 6 months before&#xD;
                  enrollment, such as cerebrovascular accidents (including temporary ischemic&#xD;
                  attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and&#xD;
                  pulmonary embolism;&#xD;
&#xD;
              14. Pregnant or breast-feeding women; fertility patients who are unwilling or unable&#xD;
                  to take effective contraceptive measures;&#xD;
&#xD;
              15. Other situations that the researcher thinks are not suitable for inclusion.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Jun-ping Zhang, Chief Physician</last_name>
    <phone>86-010-62856783</phone>
    <email>doczhjp@hotmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Sanbo Brain Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jun-ping Zhang, Chief Physician</last_name>
      <phone>86-010-62856783</phone>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>August 4, 2020</study_first_submitted>
  <study_first_submitted_qc>August 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>April 18, 2023</last_update_submitted>
  <last_update_submitted_qc>April 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Beijing Sanbo Brain Hospital</investigator_affiliation>
    <investigator_full_name>Junping Zhang</investigator_full_name>
    <investigator_title>professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Meningioma</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apatinib</mesh_term>
  </intervention_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/NCT04501705
org study id: OBU-BJ-CM-Ⅱ-008
nct id: NCT04501705
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Apatinib mesylate may be an effective treatment for recurrent atypical/malignant meningioma.
      This prospective clinical study is now planned to verify the effectiveness and safety of
      apatinib mesylate in the treatment of relapsed atypical/malignant meningioma.
Vascular endothelial growth factor VEGF is related to the abnormal angiogenesis of meningioma
      and can also activate other growth factor pathways. Meningiomas are vascular tumors. Studies
      have shown that the expression of VEGF in atypical meningiomas is twice that of benign
      meningiomas, and VEGF in anaplastic meningiomas is 10 times that of benign meningiomas.
      Therefore, anti-angiogenesis therapy may be more effective for higher grade meningiomas.
      Previous clinical studies have confirmed that anti-angiogenic drugs such as bevacizumab,
      sunitinib and PTK 787 can slow down tumor growth and prolong progression-free survival for
      recurrent atypical/malignant meningioma. In summary, apatinib mesylate may be an effective
      treatment for recurrent atypical/malignant meningioma. This prospective clinical study is now
      planned to verify the effectiveness and safety of apatinib mesylate in the treatment of
      relapsed atypical/malignant meningioma.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PFS-6 %
time frame: 6-month progression-free survival
description: 6-month progression-free survival
measure: ORR
time frame: up to 5 years
description: Objective Response Rate
measure: OS
time frame: up to 5 years
description: Overall survival
arm group label: test group
arm group type: Experimental
intervention type: Drug
intervention name: Apatinib Mesylate
description: Apatinib mesylate tablets: Orally, 500 mg, once a day, with warm water for half an hour after a meal (the time of taking the medicine every day should be the same as possible).
Continue to use 28 days as a cycle, medication until disease progression (PD), intolerable toxicity occurs or the patient withdraws informed consent. However, the longest period does not exceed 24 cycles, and the treatment after 24 cycles is determined by the investigator.
arm group label: test group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jun-ping Zhang, Chief Physician
phone: 86-010-62856783
email: doczhjp@hotmail.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Beijing Sanbo Brain Hospital
investigator full name: Junping Zhang
investigator title: professor
mesh term: Meningioma
mesh term: Recurrence
mesh term: Apatinib