<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/NCT03288272</url>
  </required_header>
  <id_info>
    <org_study_id>ERASER</org_study_id>
    <nct_id>NCT03288272</nct_id>
  </id_info>
  <brief_title>Evaluation of Repeated Whole Brain Radiotherapy Versus Best Supportive Care for Multiple Brain Metastases.</brief_title>
  <acronym>ERASER</acronym>
  <official_title>Evaluation of Repeated Whole Brain Radiotherapy Versus Best Supportive Care for Multiple Brain Metastases - the Randomized Trial ERASER.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stephanie Combs</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Technical University of Munich</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Whole Brain Radiotherapy (WBRT) has been established as the treatment standard in patients&#xD;
      with multiple cerebral metastases from solid tumors. However, intracerebral recurrence is&#xD;
      possible and a repeated WBRT may be indicated to improve intracerebral tumor control. Each&#xD;
      institutsion offers different dosing regimens, which have all been published to be safe and&#xD;
      effective. Some favor best supportive care only.&#xD;
&#xD;
      The current study protocol is aimed at evaluating primarily the toxicity as well as&#xD;
      secondarily the local and loco-regional tumor control, overall survival and QoL after&#xD;
      repeated WBRT using 2 different dose concepts (20 Gy in 10 Fx vs. 30 Gy in 15 Fx) compared to&#xD;
      BSC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      According to Nussbaum et al., 24-45% of cancer patients develop cerebral metastases during&#xD;
      the course of the disease. Brain metastases are generally associated with a poor prognosis&#xD;
      and high morbidity. Published median survival rates after WBRT are between 2 and 7 months.&#xD;
      Standard of care in multiple BM is WBRT delivered as 30 Gy in 10 fractions, leading to modest&#xD;
      palliation with a median survival of 3 to 5 months. Prognostic factors include the&#xD;
      RPA-classification, performance status, response to steroids and evidence of systemic&#xD;
      disease.&#xD;
&#xD;
      Unfortunately, intracerebral recurrence happens. For example, in the cohort of Meyners et&#xD;
      al.(2010) on WBRT in relatively radioresistant tumors, median time to recurrence was&#xD;
      4.5months and the local control rates at 6 and 12 months post radiationem were 37% and 15%,&#xD;
      respectively. Furthermore, the treatment of intracerebral recurrence after previous WBRT is&#xD;
      challenging. In case of &lt;/= 3 recurrent BM, surgery or radiosurgery (RS) are options. One&#xD;
      other option, especially in case of &gt;3 recurrent BM is repeated WBRT. In this setting, one of&#xD;
      the first reports on repeated WBRT was published by Cooper et al. in 1990. The authors&#xD;
      reported on repeated WBRT (n=52) consisting of 25 Gy in 10 fractions. Response to&#xD;
      reirradiation was seen in 42% of the patients. Furthermore, the patients improved by at least&#xD;
      one level in their neurologic function status. Survival after second therapy averaged 5&#xD;
      months. In the report by Wong et al. (1996) median dose of retreatment (n=86) was 20 Gy.&#xD;
      Resolution of symptoms was achieved in 27% of patients, partial improvement in 43% and no&#xD;
      improvement or worsening of symptoms was seen in 29% of patients. The majority of patients&#xD;
      had no significant toxicity secondary to re-irradiation. Five patients had radiographic&#xD;
      abnormalities of their brain consistent with radiation-related changes. One patient had&#xD;
      symptoms of dementia that was thought to be caused by radiotherapy. Sadikov et al. (2007)&#xD;
      reported on 72 patients who underwent repeated WBRT for recurrent or progressive BM. The&#xD;
      median survival after re-irradiation was 4.1 months. One patient was reported as having&#xD;
      memory impairment and pituitary insufficiency after 5 months of progression-free survival.&#xD;
&#xD;
      In the report by Mayer et al. on re-irradiation tolerance of the human brain -in this&#xD;
      analysis focused on recurrent glioma-, the authors concluded that radiation-induced brain&#xD;
      tissue necrosis is found to occur at normalized tolerance doses of cumulative &gt; 100 Gy.&#xD;
&#xD;
      The current study protocol is aimed at evaluating primarily the toxicity as well as&#xD;
      secondarily the local and loco-regional tumor control, overall survival and QoL after&#xD;
      repeated WBRT using 2 different dose concepts (20 Gy in 10 Fx vs. 30 Gy in 15 Fx) compared to&#xD;
      BSC.&#xD;
&#xD;
      In the present trial, the primary endpoint toxicity as well as the secondary endpoints QoL,&#xD;
      loco-regional progression-free survival, overall survival and imaging response in patients&#xD;
      previously treated with WBRT requiring repeated WBRT for intracerebral tumor progression will&#xD;
      be evaluated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>April 2016</start_date>
  <completion_date type="Anticipated">May 2018</completion_date>
  <primary_completion_date type="Anticipated">May 2018</primary_completion_date>
  <phase>Phase 2</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>Randomization Best Supportive Care, Two Radiotherapy Dosing Regimens</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Toxicity</measure>
    <time_frame>3 months</time_frame>
    <description>The primary endpoint is toxicity according to CTCAE after whole brain radiotherapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>loco-regional progression-free survival</measure>
    <time_frame>6 months</time_frame>
    <description>follow-up and local control of brain metastases as well as loco-regional control</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life (QOL)</measure>
    <time_frame>6 months</time_frame>
    <description>QOL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival</measure>
    <time_frame>6 months</time_frame>
    <description>survival after radiotherapy</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Brain Metastasases</condition>
  <arm_group>
    <arm_group_label>Arm 1 - WBRT 10 x 2 Gy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Arm 1 - WBRT 10 x 2 Gy Whole brain radiotherapy with a total dose of 20 Gy in single fractions of 2 Gy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2 - WBRT 15 x 2 Gy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Arm 2 - WBRT 15 x 2 Gy Whole brain radiotherapy with a total dose of 30 Gy in single fractions of 2 Gy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 3 - Best Supportive Care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Symptomatic treatment includes steroids, pain medication, nutritional support etc.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Whole Brain Radiotherapy</intervention_name>
    <description>Radiotherapy of the whole brain</description>
    <arm_group_label>Arm 1 - WBRT 10 x 2 Gy</arm_group_label>
    <arm_group_label>Arm 2 - WBRT 15 x 2 Gy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Best Supportive Care</intervention_name>
    <description>Best Supportive Care including nutrition, pain medication, steroids as needed</description>
    <arm_group_label>Arm 3 - Best Supportive Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  histologically confirmed malignancy&#xD;
&#xD;
          -  previous WBRT&#xD;
&#xD;
          -  MR-imaging confirmed cerebral metastases (&gt;1)&#xD;
&#xD;
          -  age ≥ 18 years of age&#xD;
&#xD;
          -  Karnofsky Performance Score ³60&#xD;
&#xD;
          -  For women with childbearing potential, (and men) adequate contraception.&#xD;
&#xD;
          -  Ability of subject to understand character and individual consequences of the clinical&#xD;
             trial&#xD;
&#xD;
          -  Written informed consent (must be available before enrolment in the trial)&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  refusal of the patients to take part in the study&#xD;
&#xD;
          -  Patients who have not yet recovered from acute high-grade toxicities of prior&#xD;
             therapies&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Participation in another clinical study or observation period of competing trials,&#xD;
             respectively&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stephanie E Combs, Prof. Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Professor and Department Chair</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Stephanie E Combs, Prof. Dr.</last_name>
    <phone>+49-89-4140-</phone>
    <phone_ext>4501</phone_ext>
    <email>stephanie.combs@tum.de</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Carmen Kessel, MA</last_name>
    <phone>+49-89-4140-</phone>
    <phone_ext>4501</phone_ext>
    <email>carmen.kessel@tum.de</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Technische Universität München (TUM), Klinikum rechts der Isar</name>
      <address>
        <city>Munich</city>
        <zip>81675</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stephanie E Combs, Prof. Dr.</last_name>
      <phone>+49-89-4140-</phone>
      <phone_ext>4501</phone_ext>
      <email>stephanie.combs@tum.de</email>
    </contact>
    <contact_backup>
      <last_name>Carmen Kessel, MA</last_name>
      <phone>+49-89-4140-</phone>
      <phone_ext>4501</phone_ext>
      <email>carmen.kessel@tum.de</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <results_reference>
    <citation>Scharp M, Hauswald H, Bischof M, Debus J, Combs SE. Re-irradiation in the treatment of patients with cerebral metastases of solid tumors: retrospective analysis. Radiat Oncol. 2014 Jan 3;9:4. doi: 10.1186/1748-717X-9-4.</citation>
    <PMID>24387239</PMID>
  </results_reference>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>May 15, 2016</study_first_submitted>
  <study_first_submitted_qc>September 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 20, 2017</study_first_posted>
  <last_update_submitted>September 16, 2017</last_update_submitted>
  <last_update_submitted_qc>September 16, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 20, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Technical University of Munich</investigator_affiliation>
    <investigator_full_name>Stephanie Combs</investigator_full_name>
    <investigator_title>Professor and Chair</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</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/NCT03288272
org study id: ERASER
nct id: NCT03288272
lead sponsor: 
has dmc: No
Whole Brain Radiotherapy (WBRT) has been established as the treatment standard in patients
      with multiple cerebral metastases from solid tumors. However, intracerebral recurrence is
      possible and a repeated WBRT may be indicated to improve intracerebral tumor control. Each
      institutsion offers different dosing regimens, which have all been published to be safe and
      effective. Some favor best supportive care only.

      The current study protocol is aimed at evaluating primarily the toxicity as well as
      secondarily the local and loco-regional tumor control, overall survival and QoL after
      repeated WBRT using 2 different dose concepts (20 Gy in 10 Fx vs. 30 Gy in 15 Fx) compared to
      BSC.
According to Nussbaum et al., 24-45% of cancer patients develop cerebral metastases during
      the course of the disease. Brain metastases are generally associated with a poor prognosis
      and high morbidity. Published median survival rates after WBRT are between 2 and 7 months.
      Standard of care in multiple BM is WBRT delivered as 30 Gy in 10 fractions, leading to modest
      palliation with a median survival of 3 to 5 months. Prognostic factors include the
      RPA-classification, performance status, response to steroids and evidence of systemic
      disease.

      Unfortunately, intracerebral recurrence happens. For example, in the cohort of Meyners et
      al.(2010) on WBRT in relatively radioresistant tumors, median time to recurrence was
      4.5months and the local control rates at 6 and 12 months post radiationem were 37% and 15%,
      respectively. Furthermore, the treatment of intracerebral recurrence after previous WBRT is
      challenging. In case of </= 3 recurrent BM, surgery or radiosurgery (RS) are options. One
      other option, especially in case of >3 recurrent BM is repeated WBRT. In this setting, one of
      the first reports on repeated WBRT was published by Cooper et al. in 1990. The authors
      reported on repeated WBRT (n=52) consisting of 25 Gy in 10 fractions. Response to
      reirradiation was seen in 42% of the patients. Furthermore, the patients improved by at least
      one level in their neurologic function status. Survival after second therapy averaged 5
      months. In the report by Wong et al. (1996) median dose of retreatment (n=86) was 20 Gy.
      Resolution of symptoms was achieved in 27% of patients, partial improvement in 43% and no
      improvement or worsening of symptoms was seen in 29% of patients. The majority of patients
      had no significant toxicity secondary to re-irradiation. Five patients had radiographic
      abnormalities of their brain consistent with radiation-related changes. One patient had
      symptoms of dementia that was thought to be caused by radiotherapy. Sadikov et al. (2007)
      reported on 72 patients who underwent repeated WBRT for recurrent or progressive BM. The
      median survival after re-irradiation was 4.1 months. One patient was reported as having
      memory impairment and pituitary insufficiency after 5 months of progression-free survival.

      In the report by Mayer et al. on re-irradiation tolerance of the human brain -in this
      analysis focused on recurrent glioma-, the authors concluded that radiation-induced brain
      tissue necrosis is found to occur at normalized tolerance doses of cumulative > 100 Gy.

      The current study protocol is aimed at evaluating primarily the toxicity as well as
      secondarily the local and loco-regional tumor control, overall survival and QoL after
      repeated WBRT using 2 different dose concepts (20 Gy in 10 Fx vs. 30 Gy in 15 Fx) compared to
      BSC.

      In the present trial, the primary endpoint toxicity as well as the secondary endpoints QoL,
      loco-regional progression-free survival, overall survival and imaging response in patients
      previously treated with WBRT requiring repeated WBRT for intracerebral tumor progression will
      be evaluated.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomization Best Supportive Care, Two Radiotherapy Dosing Regimens
primary purpose: Treatment
masking: None (Open Label)
measure: Toxicity
time frame: 3 months
description: The primary endpoint is toxicity according to CTCAE after whole brain radiotherapy.
measure: loco-regional progression-free survival
time frame: 6 months
description: follow-up and local control of brain metastases as well as loco-regional control
measure: Quality of Life (QOL)
time frame: 6 months
description: QOL
measure: Survival
time frame: 6 months
description: survival after radiotherapy
arm group label: Arm 1 - WBRT 10 x 2 Gy
arm group type: Active Comparator
description: Arm 1 - WBRT 10 x 2 Gy Whole brain radiotherapy with a total dose of 20 Gy in single fractions of 2 Gy
arm group label: Arm 2 - WBRT 15 x 2 Gy
arm group type: Active Comparator
description: Arm 2 - WBRT 15 x 2 Gy Whole brain radiotherapy with a total dose of 30 Gy in single fractions of 2 Gy
arm group label: Arm 3 - Best Supportive Care
arm group type: Active Comparator
description: Symptomatic treatment includes steroids, pain medication, nutritional support etc.
intervention type: Radiation
intervention name: Whole Brain Radiotherapy
description: Radiotherapy of the whole brain
arm group label: Arm 1 - WBRT 10 x 2 Gy
arm group label: Arm 2 - WBRT 15 x 2 Gy
intervention type: Other
intervention name: Best Supportive Care
description: Best Supportive Care including nutrition, pain medication, steroids as needed
arm group label: Arm 3 - Best Supportive Care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Stephanie E Combs, Prof. Dr.
role: Principal Investigator
affiliation: Professor and Department Chair
last name: Stephanie E Combs, Prof. Dr.
phone: +49-89-4140-
phone ext: 4501
email: stephanie.combs@tum.de
last name: Carmen Kessel, MA
phone: +49-89-4140-
phone ext: 4501
email: carmen.kessel@tum.de
facility: 
status: Recruiting
contact: 
contact backup: 
country: Germany
citation: Scharp M, Hauswald H, Bischof M, Debus J, Combs SE. Re-irradiation in the treatment of patients with cerebral metastases of solid tumors: retrospective analysis. Radiat Oncol. 2014 Jan 3;9:4. doi: 10.1186/1748-717X-9-4.
PMID: 24387239
responsible party type: Sponsor-Investigator
investigator affiliation: Technical University of Munich
investigator full name: Stephanie Combs
investigator title: Professor and Chair
mesh term: Brain Neoplasms
sharing ipd: Yes