<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/NCT04495309</url>
  </required_header>
  <id_info>
    <org_study_id>ARO-2015-1</org_study_id>
    <nct_id>NCT04495309</nct_id>
  </id_info>
  <brief_title>Metastases-directed Radiotherapy in Addition to Standard Systemic Therapy in Patients With Oligometastatic Breast Cancer</brief_title>
  <acronym>OLIGOMA</acronym>
  <official_title>Effectiveness and Tolerability of Metastases-directed Radiotherapy in Addition to Standard Systemic Therapy in Patients With Oligometastatic Breast Cancer: A Randomized Controlled Multinational and Multicenter Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital Schleswig-Holstein</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital Schleswig-Holstein</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The prognosis for patients with metastatic breast cancer has improved continuously. Systemic&#xD;
      therapies alone are not able to cure the disease permanently.&#xD;
&#xD;
      Investigators initiated this randomized controlled multinational and multicenter clinical&#xD;
      trial to analyse the impact of a local metastases-directed radiotherapy in addition to&#xD;
      standard systemic therapy in patients with oligometastatic breast cancer on progression-free&#xD;
      survival and quality of life.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Preferably ablative radiotherapy (radiosurgery, stereotactic radiotherapy, hypofractionated&#xD;
      image-guided radiotherapy (IGRT)) with few high-dose fractions. Larger lesions or lesions&#xD;
      with critical normal tissue involvement should be treated with three-dimensional conformal&#xD;
      radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) in moderate&#xD;
      hypofractionated radiotherapy (depending on the size and location of the target volume and&#xD;
      the decision of the radiooncologist). For critical organs in the target volume, standard&#xD;
      fractionated radiotherapy can be used.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 5, 2021</start_date>
  <completion_date type="Anticipated">June 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2023</primary_completion_date>
  <phase>N/A</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>First co-primary outcome measure is progression-free survival (PFS)</measure>
    <time_frame>at least 12 months after randomization</time_frame>
    <description>Co-primary progression-free survival (PFS) according to Response Evaluation Criteria In Solid Tumors (RECIST)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Second co-primary outcome measure is quality of life</measure>
    <time_frame>12 weeks after randomization</time_frame>
    <description>Co-primary quality of life according to European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer patients with 30 items (QLQ-C30) sum score</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Feasibility (per-protocol within intention-to-treat)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Proportion of participants treated per protocol</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>at least 1, up to 5 years</time_frame>
    <description>Time between randomization and death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity (number and degree of reported toxicities in both treatment arms)</measure>
    <time_frame>0 to 5 years</time_frame>
    <description>Proportion of participants with degree of toxicities as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) and by Radiation Treatment Oncology Group (RTOG) by point in time of follow-up with higher degree indicating higher intensity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neoplasia-specific quality of life</measure>
    <time_frame>quarterly up to 5 years</time_frame>
    <description>Research and Treatment of Cancer (EORTC) Quality of Life Questionaire for Cancer patients with 30 items (QLQ-C30) with different scales</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Breast cancer-specific quality of life</measure>
    <time_frame>quarterly up to 5 years</time_frame>
    <description>Research and Treatment of Cancer (EORTC) Quality of Life Questionaire for breast cancer patients with 23 items (QLQ-BR23) on 4-point Likert scales with different directions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient satisfaction</measure>
    <time_frame>12 weeks</time_frame>
    <description>Research and Treatment of Cancer (EORTC) Patient satisfaction questionnaire for cancer patients with 33 items (PATSAT-C33) on 5-point Likert scale with higher scores indicating greater satisfaction</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of adverse events</measure>
    <time_frame>0 to 5 years</time_frame>
    <description>Number of patients with adverse and serious adverse events</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">564</enrollment>
  <condition>Metastatic Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Standard</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Standard of care, i. e. no local radiotherapy in addition to standard systemic therapy (exception: palliative local treatment of symptomatic lesions where indicated)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Standard of care (standard systemic therapy) + study intervention</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Metastases-directed Radiotherapy</intervention_name>
    <description>Ablative radiotherapy (radiosurgery, stereotactic radiotherapy, hypofractionated image-guided radiotherapy (IGRT)) with few high-dose fractions</description>
    <arm_group_label>Experimental</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Metastasized breast cancer - up to 5 clinically manifest (new, progressive,&#xD;
             persistent) metastases (a lymph node metastasis and a circumscribed local recurrence&#xD;
             are each considered as one metastasis, i.e. also locoregional recurrent breast&#xD;
             carcinomas with additional hematogenic metastasis possible)&#xD;
&#xD;
          -  maximum of 3 cerebral metastases known&#xD;
&#xD;
          -  indication for palliative drug therapy (endocrine therapy and/or chemotherapy and/or&#xD;
             treatment with other substances) given according to guidelines (1st-line or further&#xD;
             therapy lines, a special regime is not specified)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2&#xD;
&#xD;
          -  local radiation of all metastases possible&#xD;
&#xD;
          -  presentation of a written declaration of consent&#xD;
&#xD;
          -  patient ≥ 18 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous radiotherapy, if this interferes with treatment within the scope of the study&#xD;
&#xD;
          -  symptomatic metastases requiring local therapy of all metastases (e.g. pain&#xD;
             radiation), a radiation indication (or other local therapy) for individual metastases&#xD;
             is not a criterion for exclusion&#xD;
&#xD;
          -  known central nervous system (CNS) metastasis without extracerebral metastasis (in&#xD;
             these cases, immediate local therapy is mandatory)&#xD;
&#xD;
          -  more than three known CNS metastases (no indication for purely local therapy of only&#xD;
             the metastases, primary whole brain radiation is indicated)&#xD;
&#xD;
          -  multifocal metastasis in one organ with impossibility to comply with the dose&#xD;
             constraints for this organ (e.g., no indication for local therapy of only the&#xD;
             metastases, primary whole brain radiation is indicated) (e.g. in the liver)&#xD;
&#xD;
          -  exclusively regional lymph node metastasis without haematogenic metastases (in these&#xD;
             cases local therapy is clearly indicated according to guidelines)&#xD;
&#xD;
          -  relevant comorbidity, if this results in restrictions for further therapy&#xD;
&#xD;
          -  Incapacity to contract or lack of informed consent&#xD;
&#xD;
          -  Pregnancy and lactation&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Patients with oligometastatic breast cancer</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jürgen Dunst, Professor</last_name>
    <role>Study Director</role>
    <affiliation>University Hospital Schleswig-Holstein</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kathrin Dellas, Professor</last_name>
    <phone>0431/500/26570</phone>
    <email>Kathrin.Dellas@uksh.de</email>
  </overall_contact>
  <location>
    <facility>
      <name>Universitätsmedizin Mannheim Klinik für Strahlentherapie und Radioonkologie</name>
      <address>
        <city>Mannheim</city>
        <state>Baden-Württemberg</state>
        <zip>68167</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elena Sperk, MD</last_name>
      <phone>0049/621 383 4241</phone>
      <email>elena.sperk@umm.de</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Praxis für Strahlentherapie und Radioonkologie am Krankenhaus Weilheim</name>
      <address>
        <city>Weilheim</city>
        <state>Bayern</state>
        <zip>82362</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Monika Panzer, MD</last_name>
      <phone>0049/88192452340</phone>
      <email>mpa@strahlentherapie-weilheim.de</email>
    </contact>
    <contact_backup>
      <last_name>Michaela Riepl, MD</last_name>
      <phone>0049/88192452340</phone>
      <email>mrp@strahlentherapie-weilheim.de</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Klinikum Frankfurt (Oder) GmbH Klinik für Strahlentherapie/Radioonkologie</name>
      <address>
        <city>Frankfurt (Oder)</city>
        <state>Brandenburg</state>
        <zip>15236</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Reinhard E. Wurm, MD</last_name>
      <phone>0049/335 548 4721</phone>
      <email>reinhard.wurm@klinikumffo.de</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Marburg Klinik für Strahlentherapie und Radioonkologie</name>
      <address>
        <city>Marburg</city>
        <state>Hessen</state>
        <zip>35033</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hilke Vorwerk, Prof.</last_name>
      <phone>0049/6421 58 66270</phone>
      <email>hilke.vorwerk@med.uni-marburg.de</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>GSR Hameln im Sana Klinikum Hameln-Pyrmont</name>
      <address>
        <city>Hameln</city>
        <state>Niedersachsen</state>
        <zip>31785</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stefan Janssen, MD</last_name>
      <phone>0049/5151 9626320</phone>
      <email>stefan.janssen@strahlentherapie.de</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Gemeinschaftspraxis für Strahlentherapie</name>
      <address>
        <city>Hildesheim</city>
        <state>Niedersachsen</state>
        <zip>31135</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Susann Popella, MD</last_name>
      <phone>0049/5121 8942 913</phone>
      <email>spopella@strahlentherapie-hildesheim.de</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>MVZ WOB GmbH Strahlentherapie</name>
      <address>
        <city>Wolfsburg</city>
        <state>Niedersachsen</state>
        <zip>38440</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marcel Ott, MD</last_name>
      <phone>0049/5361 803850</phone>
      <email>Marcel.Ott@Klinikum.Wolfsburg.de</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Strahlentherapie Bocholt Gemeinschaftspraxis und Belegabteilung am St.-Agnes-Hospital</name>
      <address>
        <city>Bocholt</city>
        <state>Nordrhein-Westfalen</state>
        <zip>46397</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eckhard Horst, MD</last_name>
      <phone>0049/2871 246540</phone>
      <email>horst@strahlentherapie-bocholt.de</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Evangelische Kliniken Gelsenkirchen Klinik für Strahlentherapie</name>
      <address>
        <city>Gelsenkirchen</city>
        <state>Nordrhein-Westfalen</state>
        <zip>45879</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rodrigo Hepp, MD</last_name>
      <phone>0049/209 160 53001</phone>
      <email>heppdelosrios@evk-ge.de</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Xcare Praxis für Strahlentherapie Saarlouis am Marienkrankenhaus</name>
      <address>
        <city>Saarlouis</city>
        <state>Saarland</state>
        <zip>66740</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sevda Toperim</last_name>
      <phone>0049/6831 161229</phone>
      <email>sevda.toperim@x-care.de</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Städtisches Klinikum Dresden, Strahlentherapie</name>
      <address>
        <city>Dresden</city>
        <state>Sachsen</state>
        <zip>01067</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andreas Schreiber, MD</last_name>
      <phone>0049/3514803500</phone>
      <email>Andreas.Schreiber@klinikum-dresden.de</email>
    </contact>
    <contact_backup>
      <last_name>Jörg Zimmer, MD</last_name>
      <phone>0049/3514803501</phone>
      <email>Zimmer-Jo@khdf.de</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Heinrich-Braun-Klinikum Zwickau gGmbH Klinik für Strahlentherapie und Radioonkologie</name>
      <address>
        <city>Zwickau</city>
        <state>Sachsen</state>
        <zip>08060</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alexander Boicev, MD</last_name>
      <phone>0049/375512802</phone>
      <email>alexander.boicev@hbk-zwickau.de</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Christian-Albrechts-University Kiel, University Medical Center Schleswig-Holstein, Campus Kiel</name>
      <address>
        <city>Kiel</city>
        <state>Schleswig-Holstein</state>
        <zip>24105</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Juergen Dunst, Prof.</last_name>
      <phone>0049/431/50026500</phone>
      <email>Juergen.Dunst@uksh.de</email>
    </contact>
    <contact_backup>
      <last_name>Kathrin Dellas, Prof.</last_name>
      <phone>0049/431/50026570</phone>
      <email>Kathrin.Dellas@uksh.de</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Johanniter-Krankenhaus Genthin-Stendal</name>
      <address>
        <city>Stendal</city>
        <zip>39576</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Evelyn Weinstrauch, MD</last_name>
      <phone>0049/3931 661504</phone>
      <email>evelyn.weinstrauch@sdl.johanniter-kliniken.de</email>
    </contact>
    <contact_backup>
      <last_name>Sachsen-Anhalt</last_name>
    </contact_backup>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>June 9, 2020</study_first_submitted>
  <study_first_submitted_qc>July 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2020</study_first_posted>
  <last_update_submitted>April 27, 2021</last_update_submitted>
  <last_update_submitted_qc>April 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Oligometastatic Breast Cancer</keyword>
  <keyword>Radiotherapy</keyword>
  <keyword>Progression-free survival (PFS)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast 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/NCT04495309
org study id: ARO-2015-1
nct id: NCT04495309
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The prognosis for patients with metastatic breast cancer has improved continuously. Systemic
      therapies alone are not able to cure the disease permanently.

      Investigators initiated this randomized controlled multinational and multicenter clinical
      trial to analyse the impact of a local metastases-directed radiotherapy in addition to
      standard systemic therapy in patients with oligometastatic breast cancer on progression-free
      survival and quality of life.
Preferably ablative radiotherapy (radiosurgery, stereotactic radiotherapy, hypofractionated
      image-guided radiotherapy (IGRT)) with few high-dose fractions. Larger lesions or lesions
      with critical normal tissue involvement should be treated with three-dimensional conformal
      radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) in moderate
      hypofractionated radiotherapy (depending on the size and location of the target volume and
      the decision of the radiooncologist). For critical organs in the target volume, standard
      fractionated radiotherapy can be used.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: First co-primary outcome measure is progression-free survival (PFS)
time frame: at least 12 months after randomization
description: Co-primary progression-free survival (PFS) according to Response Evaluation Criteria In Solid Tumors (RECIST)
measure: Second co-primary outcome measure is quality of life
time frame: 12 weeks after randomization
description: Co-primary quality of life according to European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer patients with 30 items (QLQ-C30) sum score
measure: Feasibility (per-protocol within intention-to-treat)
time frame: 12 weeks
description: Proportion of participants treated per protocol
measure: Overall survival
time frame: at least 1, up to 5 years
description: Time between randomization and death
measure: Toxicity (number and degree of reported toxicities in both treatment arms)
time frame: 0 to 5 years
description: Proportion of participants with degree of toxicities as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) and by Radiation Treatment Oncology Group (RTOG) by point in time of follow-up with higher degree indicating higher intensity
measure: Neoplasia-specific quality of life
time frame: quarterly up to 5 years
description: Research and Treatment of Cancer (EORTC) Quality of Life Questionaire for Cancer patients with 30 items (QLQ-C30) with different scales
measure: Breast cancer-specific quality of life
time frame: quarterly up to 5 years
description: Research and Treatment of Cancer (EORTC) Quality of Life Questionaire for breast cancer patients with 23 items (QLQ-BR23) on 4-point Likert scales with different directions
measure: Patient satisfaction
time frame: 12 weeks
description: Research and Treatment of Cancer (EORTC) Patient satisfaction questionnaire for cancer patients with 33 items (PATSAT-C33) on 5-point Likert scale with higher scores indicating greater satisfaction
measure: Frequency of adverse events
time frame: 0 to 5 years
description: Number of patients with adverse and serious adverse events
arm group label: Standard
arm group type: No Intervention
description: Standard of care, i. e. no local radiotherapy in addition to standard systemic therapy (exception: palliative local treatment of symptomatic lesions where indicated)
arm group label: Experimental
arm group type: Experimental
description: Standard of care (standard systemic therapy) + study intervention
intervention type: Radiation
intervention name: Metastases-directed Radiotherapy
description: Ablative radiotherapy (radiosurgery, stereotactic radiotherapy, hypofractionated image-guided radiotherapy (IGRT)) with few high-dose fractions
arm group label: Experimental
criteria: 
gender: Female
gender based: Yes
gender description: Patients with oligometastatic breast cancer
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jürgen Dunst, Professor
role: Study Director
affiliation: University Hospital Schleswig-Holstein
last name: Kathrin Dellas, Professor
phone: 0431/500/26570
email: Kathrin.Dellas@uksh.de
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
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status: Recruiting
contact: 
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status: Recruiting
contact: 
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status: Recruiting
contact: 
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status: Recruiting
contact: 
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status: Recruiting
contact: 
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status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
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facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
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country: Germany
responsible party type: Sponsor
mesh term: Breast Neoplasms