<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/NCT04425967</url>
  </required_header>
  <id_info>
    <org_study_id>M20SCP</org_study_id>
    <nct_id>NCT04425967</nct_id>
  </id_info>
  <brief_title>Short Course Of Preoperative Radiotherapy in Head and Neck-, Trunk- and Extremity Soft Tissue Sarcomas</brief_title>
  <acronym>SCOPES</acronym>
  <official_title>Short Course Of Preoperative Radiotherapy in Head and Neck-, Trunk- and Extremity Soft Tissue Sarcomas; a Randomized Phase II Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Netherlands Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Leiden University Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The Netherlands Cancer Institute</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Currently, soft tissue sarcomas (STS) are preoperatively irradiated in a conventionally&#xD;
      fractionated regimen of 25 x 2 Gy in five weeks. Recent radiobiological investigations,&#xD;
      however, suggest sensitivity to (modest) hypofractionation. Within this study, patients will&#xD;
      be randomized to receive either the conventional schedule of 25 x 2 Gy or a shorter&#xD;
      preoperative regimen of 14 x 3 Gy, in the hypothesis that both the postoperative wound&#xD;
      complication rate until 30 days after surgery, as well as the local control probability at&#xD;
      two years are comparable in both arms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Surgery is the cornerstone in the treatment of non-metastatic sarcomas. Whenever feasible the&#xD;
      resection should include a free surgical margin providing a rim of uninvolved tissue&#xD;
      surrounding the tumor. In most deep located tumors however, to preserve essential&#xD;
      neurovascular and bone structures and thus to preserve function, the margins are often&#xD;
      limited. High grade tumors are, even with wider margins, at higher risk of local failure.&#xD;
      Radiotherapy can reduce this risk of local failure.&#xD;
&#xD;
      Preoperative radiotherapy does increase the risk for early complications due to unavoidable&#xD;
      irradiation of the normal tissues surrounding the sarcoma mass, particularly for lower&#xD;
      extremity lesions (6-9).&#xD;
&#xD;
      Preoperative radiotherapy aims to reduce tumor vitality prior to resection, theoretically&#xD;
      allowing more conservative surgical therapy. Postoperative RT allows histological examination&#xD;
      of the tumor specimen, especially the margins, aiding in further treatment planning; it may&#xD;
      also be associated with fewer early wound complications. (10, 11).&#xD;
&#xD;
      In preoperative radiotherapy, as compared to postoperative radiotherapy, lower doses (50&#xD;
      versus 60 to 66 Gy) and smaller field sizes can be used, resulting in a reduced risk of late,&#xD;
      often irreversible, complications. Consequently, preoperative RT is the preferred approach in&#xD;
      many centers. Although the outcomes of combined RT and surgery are favorable, approximately&#xD;
      15% of the patients may relapse locally and about 30-50% distantly (dependent upon, among&#xD;
      others, age, histopathology, size and grade), stressing the need for further improvement.&#xD;
      These improvements should not only be sought in the domain of oncological endpoints, but also&#xD;
      in decreasing treatment burden. A reduction in treatment duration, maintaining local control&#xD;
      rates without increasing the rates of postoperative wound complications would serve the&#xD;
      latter endpoints. For this purpose, quality of life questionnaires as well as patient&#xD;
      reported outcomes measurements could come of help.Modern radiobiological investigations&#xD;
      suggest that, on average, intermediate to high-grade soft tissue sarcomas may have α/β&#xD;
      ratio's substantially below 10 Gy, justifying clinical studies exploring the possibility of&#xD;
      (modest) hypofractionation. Obviously, various subtype derived cell lines exhibit different&#xD;
      characteristics but on average an α/β ratio of 5 Gy would be a reasonable denominator for&#xD;
      sarcomas as a group. However, it is important not to exaggerate hypofractionation in a&#xD;
      setting where patients still need to undergo surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 25, 2021</start_date>
  <completion_date type="Anticipated">April 1, 2034</completion_date>
  <primary_completion_date type="Anticipated">April 1, 2025</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>
    <intervention_model_description>randomization between the standard arm A of 50 Gy in 5 weeks or arm B with hypofractination of 14x3Gy</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>the short-term toxicity</measure>
    <time_frame>30 days post operative</time_frame>
    <description>wound complications</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>local control</measure>
    <time_frame>2 years</time_frame>
    <description>percentage of patients without local failure after surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>long-term toxicity</measure>
    <time_frame>2 years</time_frame>
    <description>fibrosis, edema, joint impairment and bone fractures</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">163</enrollment>
  <condition>Soft Tissue Sarcomas</condition>
  <arm_group>
    <arm_group_label>25x2Gy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>the conventional schedule of 25 x 2 Gy, once daily fractionation in a five-week OTT</description>
  </arm_group>
  <arm_group>
    <arm_group_label>14x3Gy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>the study schedule of 14 x 3 Gy, once daily fractionation in a three-week overall treatment time</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>pre-operative radiotherapy</intervention_name>
    <description>pre-operative radiotherapy</description>
    <arm_group_label>14x3Gy</arm_group_label>
    <arm_group_label>25x2Gy</arm_group_label>
    <other_name>radiotherapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed newly diagnosed intermediate to high grade soft tissue&#xD;
             sarcoma localized to the extremities, trunk and chest wall or the head and neck area,&#xD;
             for which the standard treatment is a combination of and radiotherapy and surgery&#xD;
             (deep seated and/or &gt; 5cm in largest tumor diameter and/or an anticipated close&#xD;
             resection margin and/or grade II/III according to the FNCLCC definition);&#xD;
&#xD;
          -  • Absence of regional and/or distant disease. Patients staged by at least a CT scan of&#xD;
             the chest (. Staging may also be performed by FDG-PET scanning and or total body MRI&#xD;
             scans. Patients with an uncertain metastatic status (e.g. small indifferent lung&#xD;
             nodules) and patients with a low metastatic burden not precluding the application of&#xD;
             both preoperative radiotherapy and definitive surgery, are allowed to participate;&#xD;
&#xD;
          -  WHO Performance Status ≤ 2;&#xD;
&#xD;
          -  Able and willing to undergo preoperative radiotherapy;&#xD;
&#xD;
          -  Able and willing to undergo definitive surgery;&#xD;
&#xD;
          -  Able and willing to comply with regular follow-up visits;&#xD;
&#xD;
          -  Able and willing to complete patient reported outcome questionnaires (health-related&#xD;
             quality of life and cost effectiveness);&#xD;
&#xD;
             • Able and willing to undergo randomization;&#xD;
&#xD;
          -  Age ≥ 18 years;&#xD;
&#xD;
          -  Signed written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior malignancies; except another malignancy and disease-free for ≥ 5 years, or&#xD;
             completely resected non-melanomatous skin carcinoma or successfully treated in situ&#xD;
             carcinoma;&#xD;
&#xD;
          -  Patients with recurrent sarcomas who underwent prior radiotherapy to the target lesion&#xD;
             (if the primary sarcoma was managed by surgery only and no perioperative RT, patients&#xD;
             are eligible);&#xD;
&#xD;
          -  Ewing sarcoma and other PNET family tumors, rhabdomyosarcomas (both pediatric and&#xD;
             adult), osteosarcomas;&#xD;
&#xD;
          -  Any psychological, familial, sociological or geographical condition potentially&#xD;
             hampering compliance with the study protocol and follow-up schedule; those conditions&#xD;
             should be discussed with the patient before registration in the trial;&#xD;
&#xD;
          -  Female patients who are pregnant;&#xD;
&#xD;
          -  Intention to perform an isolated limb perfusion, instead of a tumor resection;&#xD;
&#xD;
          -  Neoadjuvant chemotherapy to be scheduled between end of radiotherapy and definitive&#xD;
             surgery (neoadjuvant chemotherapy before radiotherapy is allowed);&#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>Rick Haas, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Netherlands Cancer Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Rick Haas, MD, PhD</last_name>
    <phone>+31 20 512 9111</phone>
    <email>r.haas@nki.nl</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Astrid Scholten, MD, PhD</last_name>
    <phone>+31 20 512 9111</phone>
    <email>a.scholten@nki.nl</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Universitair Medisch Centrum Groningen</name>
      <address>
        <city>Groningen</city>
        <zip>9713GZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hans Langendijk, MD, PhD</last_name>
      <phone>+31 50 361 5532</phone>
      <email>j.a.langendijk@umcg.nl</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Leids Universitair Medisch Centrum</name>
      <address>
        <city>Leiden</city>
        <zip>2333ZA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lisette M Wiltink, MD, PhD</last_name>
      <phone>(071) 526 91 11</phone>
      <email>l.m.wiltink@lumc.nl</email>
    </contact>
    <contact_backup>
      <last_name>Stijn Krol, MD, PhD</last_name>
      <phone>(071) 526 91 11</phone>
      <email>a.d.g.krol@lumc.nl</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Radboudumc</name>
      <address>
        <city>Nijmegen</city>
        <zip>6525GA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Petra Braam, MD,PhD</last_name>
      <phone>+31243614023</phone>
      <email>p.braam@radboudumc.nl</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Erasmus Medical Centre</name>
      <address>
        <city>Rotterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joost Nuyttens, MD</last_name>
      <email>j.nuyttens@erasmusmc.nl</email>
    </contact>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>July 21, 2023</last_update_submitted>
  <last_update_submitted_qc>July 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>preoperative radiotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcoma</mesh_term>
  </condition_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/NCT04425967
org study id: M20SCP
nct id: NCT04425967
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Currently, soft tissue sarcomas (STS) are preoperatively irradiated in a conventionally
      fractionated regimen of 25 x 2 Gy in five weeks. Recent radiobiological investigations,
      however, suggest sensitivity to (modest) hypofractionation. Within this study, patients will
      be randomized to receive either the conventional schedule of 25 x 2 Gy or a shorter
      preoperative regimen of 14 x 3 Gy, in the hypothesis that both the postoperative wound
      complication rate until 30 days after surgery, as well as the local control probability at
      two years are comparable in both arms.
Surgery is the cornerstone in the treatment of non-metastatic sarcomas. Whenever feasible the
      resection should include a free surgical margin providing a rim of uninvolved tissue
      surrounding the tumor. In most deep located tumors however, to preserve essential
      neurovascular and bone structures and thus to preserve function, the margins are often
      limited. High grade tumors are, even with wider margins, at higher risk of local failure.
      Radiotherapy can reduce this risk of local failure.

      Preoperative radiotherapy does increase the risk for early complications due to unavoidable
      irradiation of the normal tissues surrounding the sarcoma mass, particularly for lower
      extremity lesions (6-9).

      Preoperative radiotherapy aims to reduce tumor vitality prior to resection, theoretically
      allowing more conservative surgical therapy. Postoperative RT allows histological examination
      of the tumor specimen, especially the margins, aiding in further treatment planning; it may
      also be associated with fewer early wound complications. (10, 11).

      In preoperative radiotherapy, as compared to postoperative radiotherapy, lower doses (50
      versus 60 to 66 Gy) and smaller field sizes can be used, resulting in a reduced risk of late,
      often irreversible, complications. Consequently, preoperative RT is the preferred approach in
      many centers. Although the outcomes of combined RT and surgery are favorable, approximately
      15% of the patients may relapse locally and about 30-50% distantly (dependent upon, among
      others, age, histopathology, size and grade), stressing the need for further improvement.
      These improvements should not only be sought in the domain of oncological endpoints, but also
      in decreasing treatment burden. A reduction in treatment duration, maintaining local control
      rates without increasing the rates of postoperative wound complications would serve the
      latter endpoints. For this purpose, quality of life questionnaires as well as patient
      reported outcomes measurements could come of help.Modern radiobiological investigations
      suggest that, on average, intermediate to high-grade soft tissue sarcomas may have α/β
      ratio's substantially below 10 Gy, justifying clinical studies exploring the possibility of
      (modest) hypofractionation. Obviously, various subtype derived cell lines exhibit different
      characteristics but on average an α/β ratio of 5 Gy would be a reasonable denominator for
      sarcomas as a group. However, it is important not to exaggerate hypofractionation in a
      setting where patients still need to undergo surgery.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: randomization between the standard arm A of 50 Gy in 5 weeks or arm B with hypofractination of 14x3Gy
primary purpose: Treatment
masking: None (Open Label)
measure: the short-term toxicity
time frame: 30 days post operative
description: wound complications
measure: local control
time frame: 2 years
description: percentage of patients without local failure after surgery
measure: long-term toxicity
time frame: 2 years
description: fibrosis, edema, joint impairment and bone fractures
arm group label: 25x2Gy
arm group type: Active Comparator
description: the conventional schedule of 25 x 2 Gy, once daily fractionation in a five-week OTT
arm group label: 14x3Gy
arm group type: Experimental
description: the study schedule of 14 x 3 Gy, once daily fractionation in a three-week overall treatment time
intervention type: Radiation
intervention name: pre-operative radiotherapy
description: pre-operative radiotherapy
arm group label: 14x3Gy
arm group label: 25x2Gy
other name: radiotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Rick Haas, MD, PhD
role: Principal Investigator
affiliation: The Netherlands Cancer Institute
last name: Rick Haas, MD, PhD
phone: +31 20 512 9111
email: r.haas@nki.nl
last name: Astrid Scholten, MD, PhD
phone: +31 20 512 9111
email: a.scholten@nki.nl
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Netherlands
responsible party type: Sponsor
mesh term: Sarcoma
sharing ipd: No