<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/NCT04501718</url>
  </required_header>
  <id_info>
    <org_study_id>OBU-BJ-MB-II-001</org_study_id>
    <nct_id>NCT04501718</nct_id>
  </id_info>
  <brief_title>Apatinib Combined With Temozolomide and Etoposide Capsules in the Treatment of Recurrent Medulloblastoma in Children</brief_title>
  <official_title>A Single Arm Clinical Phase Ⅱ Study of Apatinib Combined With Temozolomide and Etoposide Capsules in the Treatment of Recurrent Medulloblastoma in Children</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>
      This study is a prospective single-center clinical study, which aims to observe and evaluate&#xD;
      the efficacy and safety of apatinib combined with temozolomide and oral etoposide in the&#xD;
      treatment of recurrent medulloblastoma in children.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This research plan is implemented in accordance with GCP principles in Sanbo Brain Hospital&#xD;
      of Capital Medical University.&#xD;
&#xD;
      Subjects are screened into the group. If the following conditions do not occur (the subject&#xD;
      withdraws the informed consent, the drug side effects are intolerable, the investigator&#xD;
      thinks it is not suitable for further testing, etc.), the expected research treatment for&#xD;
      each subject It will continue until tumor progression or death confirmed by imaging studies,&#xD;
      but not more than 2 years. Observe the effectiveness index and safety index during the test.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 28, 2020</start_date>
  <completion_date type="Anticipated">August 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2024</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>Objective Response Rate (ORR)</measure>
    <time_frame>up to 4 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>up to 4 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>up to 4 years</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">44</enrollment>
  <condition>Recurrent Medulloblastoma</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 Combined With Temozolomide and Etoposide Capsules</intervention_name>
    <description>Apatinib mesylate tablets: Oral, 250mg, qd. Take the medicine with warm water half an hour after a meal (the daily medicine should be taken at the same time as possible).&#xD;
28 days is a cycle, and the medication is administered until the disease progresses (PD), intolerable toxicity occurs or the patient withdraws informed consent. The longest period does not exceed 12 cycles. The treatment after 12 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 2-21 (at the time of diagnosis), no gender limit.&#xD;
&#xD;
          2. After biopsy or surgery, the first postoperative pathological diagnosis is&#xD;
             medulloblastoma.&#xD;
&#xD;
          3. The recurrence of the tumor is confirmed by MRI, that is, the diameter of the lesion&#xD;
             on the enhanced MRI image is ≥1cm, and ≥2 slices (slice spacing 5mm) are visible; or&#xD;
             after another biopsy or surgery, the pathological diagnosis is medulloblastoma.&#xD;
&#xD;
          4. The time interval from the last radiotherapy is ≥4 weeks.&#xD;
&#xD;
          5. 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. If you receive nitrosourea&#xD;
             chemotherapeutics before enrollment, the interval between enrollment and the last&#xD;
             chemotherapy is ≥6 weeks.&#xD;
&#xD;
          6. The interval between the last biopsy or surgery is ≥2 weeks.&#xD;
&#xD;
          7. KPS score ≥50 (patient&gt; 12 years old), or Lansky score ≥ 50 (patient ≤ 12 years old).&#xD;
&#xD;
          8. If the patient is taking glucocorticoid therapy, the hormone dosage has stabilized or&#xD;
             decreased for at least 1 week before the baseline MRI.&#xD;
&#xD;
          9. The expected survival time is ≥12 weeks.&#xD;
&#xD;
         10. 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; 11. The ECG shows that the heart rate is in the normal range (55-100&#xD;
        beats/min), the QT interval is normal or slightly prolonged (QTc&lt;480ms), the T wave is&#xD;
        normal or low, and the ST segment is normal or non-specific changes.&#xD;
&#xD;
        12. The 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; male patients of childbearing age should&#xD;
             agree to During the observation period and within 8 weeks after the last&#xD;
             administration, use appropriate methods of contraception.&#xD;
&#xD;
             14. Patients voluntarily provide 25-30 slices of tumor tissue after the last biopsy or&#xD;
             surgery.&#xD;
&#xD;
             15. The patient has normal swallowing function and can swallow capsules. 16. The&#xD;
             patient voluntarily joined the study and signed an informed consent form (ICF).&#xD;
&#xD;
             17. Those who are expected to have good compliance can follow up the efficacy and&#xD;
             adverse reactions as required by the plan.&#xD;
&#xD;
             Exclusion Criteria:&#xD;
&#xD;
               1. Past application of anti-tumor angiogenesis drugs;&#xD;
&#xD;
               2. Those who are known to be allergic to any component of temozolomide, apatinib,&#xD;
                  and etoposide;&#xD;
&#xD;
               3. Are using antiepileptic drugs that induce liver drug enzymes, unless they have&#xD;
                  been replaced with antiepileptic drugs that are non-hepatic drug enzymes at least&#xD;
                  2 weeks away from enrollment;&#xD;
&#xD;
               4. Patients with other malignant tumors, unless they have survived without&#xD;
                  progression for 5 years and the researcher believes that the risk of recurrence&#xD;
                  is low or patients with carcinoma in situ;&#xD;
&#xD;
               5. People 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;
               6. Suffering from severe cardiovascular disease; T wave inverted or high tip of ECG,&#xD;
                  ST segment specific changes.&#xD;
&#xD;
               7. Urine routine test indicates urine protein ≥(++), or 24-hour urine protein ≥1.0g;&#xD;
&#xD;
               8. 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;
               9. 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;
              10. There is an infection that is difficult to control;&#xD;
&#xD;
              11. Have had significant clinically significant bleeding symptoms or a clear bleeding&#xD;
                  tendency within 3 months before enrollment, such as gastrointestinal bleeding,&#xD;
                  hemorrhagic gastric ulcer, gastrointestinal perforation, fecal occult blood++ and&#xD;
                  above at baseline, intratumoral or Intracranial hemorrhage, or suffering from&#xD;
                  vasculitis, etc.;&#xD;
&#xD;
              12. 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;
              13. Pregnant or breast-feeding women; fertility patients who are unwilling or unable&#xD;
                  to take effective contraceptive measures;&#xD;
&#xD;
              14. Other situations that the researcher thinks are not suitable for inclusion.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Jun-ping Zhang</last_name>
    <phone>86-010-62856798</phone>
    <email>doczhjp@hotmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Beijing Sanbo Brain Hospital</name>
      <address>
        <city>Beijing</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jun-ping Zhang</last_name>
      <phone>86-010-62856798</phone>
      <email>doczhjp@hotmail.com</email>
    </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 5, 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>Medulloblastoma</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Etoposide</mesh_term>
    <mesh_term>Temozolomide</mesh_term>
    <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/NCT04501718
org study id: OBU-BJ-MB-II-001
nct id: NCT04501718
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This study is a prospective single-center clinical study, which aims to observe and evaluate
      the efficacy and safety of apatinib combined with temozolomide and oral etoposide in the
      treatment of recurrent medulloblastoma in children.
This research plan is implemented in accordance with GCP principles in Sanbo Brain Hospital
      of Capital Medical University.

      Subjects are screened into the group. If the following conditions do not occur (the subject
      withdraws the informed consent, the drug side effects are intolerable, the investigator
      thinks it is not suitable for further testing, etc.), the expected research treatment for
      each subject It will continue until tumor progression or death confirmed by imaging studies,
      but not more than 2 years. Observe the effectiveness index and safety index during the test.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate (ORR)
time frame: up to 4 years
measure: Progression-free survival (PFS)
time frame: up to 4 years
measure: Overall survival (OS)
time frame: up to 4 years
arm group label: Test group
arm group type: Experimental
intervention type: Drug
intervention name: Apatinib Combined With Temozolomide and Etoposide Capsules
description: Apatinib mesylate tablets: Oral, 250mg, qd. Take the medicine with warm water half an hour after a meal (the daily medicine should be taken at the same time as possible).
28 days is a cycle, and the medication is administered until the disease progresses (PD), intolerable toxicity occurs or the patient withdraws informed consent. The longest period does not exceed 12 cycles. The treatment after 12 cycles is determined by the investigator.
arm group label: Test group
criteria: 
gender: All
minimum age: 2 Years
maximum age: 21 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jun-ping Zhang
phone: 86-010-62856798
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: Medulloblastoma
mesh term: Recurrence
mesh term: Etoposide
mesh term: Temozolomide
mesh term: Apatinib
sharing ipd: No