<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/NCT03778541</url>
  </required_header>
  <id_info>
    <org_study_id>LBM-RCT</org_study_id>
    <nct_id>NCT03778541</nct_id>
  </id_info>
  <brief_title>HFSRT With Concurrent TMZ for Large BMs</brief_title>
  <official_title>Hypofractionated Radiotherapy With Concurrent Temozolomide for Large Brain Metastases: a Multi-center Randomized Phase III Trial</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>No</has_dmc>
    <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>
      A multi-center randomized phase III trial was conducted to investigate the feasibility and&#xD;
      safety of adding temozolomide to hypofractionated stereotactic radiotherapy for large brain&#xD;
      metastases.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A previous single arm phase II trial and propensity- matched study of our institution have&#xD;
      shown that HFSRT combined with concurrent TMZ was safe and efficient for patients with BMs of&#xD;
      ≥ 6cc in volume. The 1-year local control, intracranial progression free survival,&#xD;
      progression free survival and overall survival rates were better than HFSRT alone group.&#xD;
      Thus, the investigator conducted this randomized phase III trial to broad the sample size and&#xD;
      verify our previous results. To finish the study in time, the investigator designed a&#xD;
      multi-center trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">December 3, 2018</start_date>
  <completion_date type="Anticipated">December 3, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 3, 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>patients were randomized to 2 parallel groups, namely the concurrent chemoradiotherapy group and radiotherapy alone group</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>intracranial progression free survival (IPFS) rate</measure>
    <time_frame>up to 2 years</time_frame>
    <description>IPFS was defined as the interval from the beginning of radiation to any intracranial progression</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>local control rate</measure>
    <time_frame>up to 2 years</time_frame>
    <description>the control rate of treated lesions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brain metastasis-specific survival (BMSS) rate</measure>
    <time_frame>up to 2 years</time_frame>
    <description>BMSS was defined as the internal from the beginning of RT to death caused by BM</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival (OS) rate</measure>
    <time_frame>up to 2 years</time_frame>
    <description>OS was defined as the internal from the beginning of RT to death caused by any reason</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 and NRG/RTOG CNS toxicities criteria</measure>
    <time_frame>acute toxicities: up to 3 months after RT; Late toxicities: up to 2 years after RT</time_frame>
    <description>the toxicities caused by RT and (or) Chemotherapy</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">224</enrollment>
  <condition>Brain Metastases</condition>
  <condition>Chemotherapy</condition>
  <condition>Radiotherapy</condition>
  <arm_group>
    <arm_group_label>CRT group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patients with brain metastases of more than 6 cc and treated with fractionated stereotactic radiotherapy plus concomitant Temozolomide.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RT group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>patients with brain metastases of more than 6 cc and treated with fractionated stereotactic radiotherapy alone.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Temozolomide</intervention_name>
    <description>75mg/m2/d concurrent with radiotherapy, taken for at least 20 days.</description>
    <arm_group_label>CRT group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>hypofractionated radiotherapy</intervention_name>
    <description>the regular radiation dose prescription is 52 Gy in 13 fractions or 52.5 Gy in 15 fractions.</description>
    <arm_group_label>CRT group</arm_group_label>
    <arm_group_label>RT group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  histologic or cytological diagnosis of primary tumor and conformed brain metastases by&#xD;
             enhanced MRI or CT;&#xD;
&#xD;
          -  the number of BMs ≤ 3&#xD;
&#xD;
          -  the tumor volume ≥6cc, or maximum diameter of BMs≥ 3cm;&#xD;
&#xD;
          -  Karnofsky performance score (KPS)≥60, or KPS≥40 but simply caused by BMs;&#xD;
&#xD;
          -  Age: 18-75 years old;&#xD;
&#xD;
          -  Adequate function of major organs, and blood test reached the following level:&#xD;
             WBC≥4.0x109/L, NEU≥1.5x109/L Hemoglobin≥110 g/L, Platelets≥100 x109/L; Liver function&#xD;
             test results&lt;1.5 times the institutional upper limit of normal (ULN); BUN and Cr:&#xD;
             within the normal range.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  patient with other clinically significant diseases (e.g. myocardial infarction within&#xD;
             the past 6 months, severe arrhythmia);&#xD;
&#xD;
          -  unable or unwilling to comply with the study protocol;&#xD;
&#xD;
          -  patient whose survival expectancy was less than 3 months;&#xD;
&#xD;
          -  the large BM locates in brainstem;&#xD;
&#xD;
          -  patient who anticipated in other clinical trials of brain metastases;&#xD;
&#xD;
          -  the large lesions have been treated with SRT in other hospitals;&#xD;
&#xD;
          -  pregnant patients or female patients whose HCG is positive.&#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>Jianping Xiao, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jianping Xiao, Dr</last_name>
    <phone>+8613811026919</phone>
    <email>jpxiao8@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Chinese Academy of Medical Sciences</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100021</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jianping Xiao, Dr</last_name>
      <phone>86-13811026919</phone>
      <email>jpxiao8@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>December 9, 2018</study_first_submitted>
  <study_first_submitted_qc>December 17, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>July 22, 2019</last_update_submitted>
  <last_update_submitted_qc>July 22, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 23, 2019</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>Jianping Xiao</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Brain Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Temozolomide</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/NCT03778541
org study id: LBM-RCT
nct id: NCT03778541
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
A multi-center randomized phase III trial was conducted to investigate the feasibility and
      safety of adding temozolomide to hypofractionated stereotactic radiotherapy for large brain
      metastases.
A previous single arm phase II trial and propensity- matched study of our institution have
      shown that HFSRT combined with concurrent TMZ was safe and efficient for patients with BMs of
      ≥ 6cc in volume. The 1-year local control, intracranial progression free survival,
      progression free survival and overall survival rates were better than HFSRT alone group.
      Thus, the investigator conducted this randomized phase III trial to broad the sample size and
      verify our previous results. To finish the study in time, the investigator designed a
      multi-center trial.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: patients were randomized to 2 parallel groups, namely the concurrent chemoradiotherapy group and radiotherapy alone group
primary purpose: Treatment
masking: None (Open Label)
measure: intracranial progression free survival (IPFS) rate
time frame: up to 2 years
description: IPFS was defined as the interval from the beginning of radiation to any intracranial progression
measure: local control rate
time frame: up to 2 years
description: the control rate of treated lesions
measure: Brain metastasis-specific survival (BMSS) rate
time frame: up to 2 years
description: BMSS was defined as the internal from the beginning of RT to death caused by BM
measure: overall survival (OS) rate
time frame: up to 2 years
description: OS was defined as the internal from the beginning of RT to death caused by any reason
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 and NRG/RTOG CNS toxicities criteria
time frame: acute toxicities: up to 3 months after RT; Late toxicities: up to 2 years after RT
description: the toxicities caused by RT and (or) Chemotherapy
arm group label: CRT group
arm group type: Experimental
description: patients with brain metastases of more than 6 cc and treated with fractionated stereotactic radiotherapy plus concomitant Temozolomide.
arm group label: RT group
arm group type: Active Comparator
description: patients with brain metastases of more than 6 cc and treated with fractionated stereotactic radiotherapy alone.
intervention type: Drug
intervention name: Temozolomide
description: 75mg/m2/d concurrent with radiotherapy, taken for at least 20 days.
arm group label: CRT group
intervention type: Radiation
intervention name: hypofractionated radiotherapy
description: the regular radiation dose prescription is 52 Gy in 13 fractions or 52.5 Gy in 15 fractions.
arm group label: CRT group
arm group label: RT group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Jianping Xiao, Dr
role: Principal Investigator
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
last name: Jianping Xiao, Dr
phone: +8613811026919
email: jpxiao8@163.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
investigator full name: Jianping Xiao
investigator title: Principal Investigator
mesh term: Neoplasm Metastasis
mesh term: Brain Neoplasms
mesh term: Temozolomide
sharing ipd: No