<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/NCT02986516</url>
  </required_header>
  <id_info>
    <org_study_id>ISG SACRO</org_study_id>
    <nct_id>NCT02986516</nct_id>
  </id_info>
  <brief_title>Sacral Chordoma: Surgery Versus Definitive Radiation Therapy in Primary Localized Disease</brief_title>
  <acronym>SACRO</acronym>
  <official_title>Title of Study: SAcral Chordoma: a Randomized &amp; Observational Study on Surgery Versus Definitive Radiation Therapy in Primary Localized Disease (SACRO)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Italian Sarcoma Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Italian Sarcoma Group</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>
      Comparative study on surgery versus definitive radiation therapy in primary localized sacral&#xD;
      chordoma&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      International, multicenter, comparative, open-label, parallel-group, mixed&#xD;
      Observational-Randomized Controlled Trial.&#xD;
&#xD;
      All the patients, who are candidate for the study will receive full information on the&#xD;
      characteristics, potential effectiveness and side effects of the two alternatives treatments:&#xD;
      radiotherapy (RT) and surgical treatment Eligible patients will be asked to be randomized in&#xD;
      order to receive treatment A (surgery, with or without RT) or treatment B (definitive RT) Who&#xD;
      will refuse randomization will be included in the Prospective Cohort Study (PCS) and will be&#xD;
      treated accordingly to their choice (treatment option A or treatment option B).&#xD;
&#xD;
      The same radiotherapy and surgical regimen will be administered in the PCS and in the&#xD;
      Randomized Clinical Trial (RCT) cohort&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 16, 2017</start_date>
  <completion_date type="Anticipated">September 2024</completion_date>
  <primary_completion_date type="Anticipated">September 2024</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>Relapse Free Survival (RFS)</measure>
    <time_frame>5 years</time_frame>
    <description>The time from randomization or treatment start date to the date of local disease relapse, distant disease relapse, second primary malignancy or death from any cause, whichever occurred first.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>The patients will be followed in term of Overall Survival, for all the study period (expected average: 10 years)</time_frame>
    <description>The time from randomization or treatment start date to the date of death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival Post Progression (SPP)</measure>
    <time_frame>Expected average: 36 months</time_frame>
    <description>The time from local disease relapse, distant disease relapse or second primary malignancy, whichever occurred first, to the date of death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Local Relapse Failure (LRF)</measure>
    <time_frame>Expected average: 60 months</time_frame>
    <description>The time from randomization or treatment start date to the date of local disease relapse</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Distant Relapse Failure (DRF)</measure>
    <time_frame>Expected average: 60 months</time_frame>
    <description>The time from randomization or treatment start date to the date of distant disease relapse</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best Response rate to definitive radiotherapy</measure>
    <time_frame>At 12 months, 2 years and 5 years after radiotherapy</time_frame>
    <description>Best Response rate to definitive radiotherapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to best response rate to definitive radiotherapy</measure>
    <time_frame>At 12 months, 2 years and 5 years after radiotherapy</time_frame>
    <description>Time to best response rate to definitive radiotherapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events Incidence</measure>
    <time_frame>At end of treatment , 6 months , 12 months 2 years and 5 years after surgery or radiotherapy</time_frame>
    <description>Adverse Events incidence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of quality of life measured with Functional Assessment of Cancer Therapy General</measure>
    <time_frame>every 6 months (expected average: 5 years)</time_frame>
    <description>Evaluation of quality of life measured with Functional Assessment of Cancer Therapy General</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of quality of life measured with Brief Inventory Pain questionnaires</measure>
    <time_frame>every 6 months (expected average: 5 years)</time_frame>
    <description>Evaluation of quality of life measured with Brief Inventory Pain questionnaires</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Chordoma</condition>
  <arm_group>
    <arm_group_label>Randomized Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants who will decided to undergo to randomization, will receive surgical treatment or definitive radiotherapy according with randomization assignment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Prospective Cohort</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants who will not decide to be randomized, will received the surgical or definite radiotherapy treatment according to their choice</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Randomized Cohort</intervention_name>
    <description>Surgical treatment with different approach, based on the characteristics of the tumor or definitive high dose radiotherapy (carbon ion radiotherapy, proton-therapy, mixed photons-proton therapy) will be assigned by randomization</description>
    <arm_group_label>Randomized Cohort</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Prospective cohort</intervention_name>
    <description>Surgical treatment or definitive high dose radiotherapy will be selected by the patients and will be prospectively evaluated</description>
    <arm_group_label>Prospective Cohort</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed diagnosis (brachyury expression) of primary sacral&#xD;
             chordoma,of any diameter and arising at any site from S1 to coccyx.&#xD;
&#xD;
          -  Age≥18years&#xD;
&#xD;
          -  ECOG-performance status (PS) 0-2&#xD;
&#xD;
          -  No previous antineoplastic therapy&#xD;
&#xD;
          -  Macroscopic tumor detectable at MRI/CT scan&#xD;
&#xD;
          -  Patient amenable for surgery&#xD;
&#xD;
          -  Patient amenable for RT&#xD;
&#xD;
          -  Written informed consent given before the enrolment, according to International&#xD;
             Conference on Harmonisation/good clinical practice (ICH/GCP).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Distant metastasis&#xD;
&#xD;
          -  Inability to maintain treatment position&#xD;
&#xD;
          -  Prior radiotherapy to the pelvic region&#xD;
&#xD;
          -  Prior therapy for sacral chordoma (including surgery, cryoablation, hyperthermia, etc)&#xD;
&#xD;
          -  Local conditions that increase the risk of RT toxicity (tumor ulcerated skin&#xD;
             infiltration, non-healing soft tissue infection, fistula in treatment field)&#xD;
&#xD;
          -  Rectal wall infiltration&#xD;
&#xD;
          -  General conditions that increase the risk of RT toxicity (active sclerodermia,&#xD;
             xeroderma pigmentosum, cutaneous porphyria)&#xD;
&#xD;
          -  Presence of a second active cancer (with the exception of non-melanoma skin cancer&#xD;
             in-situ cervix neoplasia and other in-situ neoplasia)&#xD;
&#xD;
          -  Severe comorbidities resulting in a prognosis of less than 6 months&#xD;
&#xD;
          -  Inability to give informed consent&#xD;
&#xD;
          -  Other malignancy within the last 5 years&#xD;
&#xD;
          -  Performance status ≥ 2 (ECOG).&#xD;
&#xD;
          -  Significant cardiovascular disease (for example, dyspnea &gt; 2 NYHA)&#xD;
&#xD;
          -  Significant systemic diseases grade &gt;3 on the NCI-CTCAE v4.03 scale, that limit&#xD;
             patient availability, or according to investigator judgment may contribute&#xD;
             significantly to treatment toxicity&#xD;
&#xD;
          -  Women who are pregnant or breast-feeding&#xD;
&#xD;
          -  Psychological, familial, social or geographic circumstances that limit the patient's&#xD;
             ability to comply with the protocol or informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alessandro Gronchi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Istituto Nazionale Tumori Milan-Italy</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Piero Fossati, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>MedAustron Graz-Austria</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Alessandro Gronchi, MD</last_name>
    <phone>+390223903714</phone>
    <email>alessandro.gronchi@istitutotumori.mi.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>ISG Clinical Trial Center</last_name>
    <email>clinicaltrials@italiansarcomagroup.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Medical University of Graz</name>
      <address>
        <city>Graz</city>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andreas Leithner, MD</last_name>
    </contact>
    <investigator>
      <last_name>Andreas Leithner, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>EBG GmbH MedAustron</name>
      <address>
        <city>Wiener Neustadt</city>
        <state>Österreich</state>
        <zip>2700</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Piero Fossati, MD</last_name>
      <phone>+43 2622 26100</phone>
      <phone_ext>408</phone_ext>
      <email>piero.fossati@medaustron.at</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Medical Faculty Carl Gustav Carus Faculty of Medicine, Department of Radiation Oncology,</name>
      <address>
        <city>Dresden</city>
        <country>Germany</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Mechthild Krause, Prof/MD</last_name>
    </contact>
    <investigator>
      <last_name>Mechthild Krause, Prof/MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Hospital Carl Gustav Carus Dresden</name>
      <address>
        <city>Dresden</city>
        <country>Germany</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Mechthild Krause, MD</last_name>
    </contact>
    <investigator>
      <last_name>Mechthild Krause, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Hospital Essen. West German Proton Therapy Center Essen</name>
      <address>
        <city>Essen</city>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Beate Timmermann, MD</last_name>
    </contact>
    <investigator>
      <last_name>Beate Timmermann, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Heidelberg Ion-Beam Therapy Center - HIT</name>
      <address>
        <city>Heidelberg</city>
        <country>Germany</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Matthias Uhl, MD</last_name>
    </contact>
    <investigator>
      <last_name>Matthias Uhl, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>National Center for Spinal Disorders</name>
      <address>
        <city>Budapest</city>
        <country>Hungary</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Peter P Varga, MD</last_name>
    </contact>
    <investigator>
      <last_name>Peter P Varga, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Istituto Nazionale dei Tumori</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alessandro Gronchi, MD</last_name>
      <email>alessandro.gronchi@istitutotumori.mi.it</email>
    </contact>
    <investigator>
      <last_name>Alessandro Gronchi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Istituto Ortopedico Rizzoli</name>
      <address>
        <city>Bologna</city>
        <zip>40136</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alessandro Gasbarrini, MD</last_name>
      <phone>+390516366</phone>
      <phone_ext>066</phone_ext>
      <email>alessandro.gasbarrini@ior.it</email>
    </contact>
    <investigator>
      <last_name>Alessandro Gasbarrini, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero-Universitaria Careggi</name>
      <address>
        <city>Firenze</city>
        <zip>50134</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Domenico A Campanacci, MD</last_name>
    </contact>
    <investigator>
      <last_name>Domenico A Campanacci, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Istituto Clinico Humanitas</name>
      <address>
        <city>Milano</city>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ferdinando Cananzi, MD</last_name>
      <email>ferdinando.cananzi@hunimed.eu</email>
    </contact>
    <investigator>
      <last_name>Ferdinando Cananzi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>I.R.C.C.S. Istituto Ortopedico Galeazzi</name>
      <address>
        <city>Milano</city>
        <zip>20161</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Centro Nazionale di Adroterapia Oncologica - CNAO</name>
      <address>
        <city>Pavia</city>
        <zip>27100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maria Rosaria Fiore, MD</last_name>
      <email>MariaRosaria.Fiore@Cnao.it</email>
    </contact>
    <investigator>
      <last_name>Maria Rosaria Fiore, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>II Clinica Universitaria Ortopedia e Traumatologia AO Pisa</name>
      <address>
        <city>Pisa</city>
        <zip>56124</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lorenzo Andreani, MD</last_name>
      <email>lorenzo.andreani.unipi@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Lorenzo Andreani, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Istituto Regina Elena - IFO</name>
      <address>
        <city>Rome</city>
        <zip>00100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maria Grazia Petrongari, MD</last_name>
      <phone>+39065266</phone>
      <phone_ext>6894</phone_ext>
      <email>mariagrazia.petrongari@ifo.gov.it</email>
    </contact>
    <investigator>
      <last_name>Maria Grazia Petrongari, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Agenzia Provinciale per la Protonterapia - AtreP</name>
      <address>
        <city>Trento</city>
        <zip>38122</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Saitama Medical Center</name>
      <address>
        <city>Saitama</city>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Toru Akiyama, MD</last_name>
    </contact>
    <investigator>
      <last_name>Toru Akiyama, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Netherlands Cancer Institute</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>R LM Haas, MD</last_name>
    </contact>
    <investigator>
      <last_name>R LM Haas, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Leiden University Medical Center</name>
      <address>
        <city>Leiden</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Sander Dijkstra, MD</last_name>
    </contact>
    <investigator>
      <last_name>Sander Dijkstra, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Norwegian Radium Hospital/Oslo Univeristi Hospital</name>
      <address>
        <city>Oslo</city>
        <zip>N-0424</zip>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Øyvind S. Bruland, MD</last_name>
      <phone>+47 22 93 47</phone>
      <phone_ext>67</phone_ext>
      <email>osb@ous-hf.no</email>
    </contact>
    <contact_backup>
      <last_name>Øyvind S. Bruland, MD</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie</name>
      <address>
        <city>Warsaw</city>
        <country>Poland</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>H. Val D'Hebron</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ramona V. Capdevila, MD</last_name>
    </contact>
    <investigator>
      <last_name>Ramona V. Capdevila, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hosptial San Pau</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>H. San Carlos</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Gloria M. Ospina, MD</last_name>
    </contact>
    <investigator>
      <last_name>Gloria M. Ospina</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocío</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nadia Hindi, MD</last_name>
    </contact>
    <investigator>
      <last_name>Nadia Hindi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Doctor Peset</name>
      <address>
        <city>Valencia</city>
        <zip>46017</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Antonio M. Benlloch, MD</last_name>
      <email>antonio.martin@uv.es</email>
    </contact>
    <investigator>
      <last_name>Antonio M. Benlloch, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Royal Orthopaedic Hospital</name>
      <address>
        <city>Birmingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Lee Jeys, MD</last_name>
    </contact>
    <investigator>
      <last_name>Lee Jeys, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Royal National Orthopaedic Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Rob Pollock, MD</last_name>
    </contact>
    <investigator>
      <last_name>Rob Pollock, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Netherlands</country>
    <country>Norway</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Stiller CA, Trama A, Brewster DH, Verne J, Bouchardy C, Navarro C, Chirlaque MD, Marcos-Gragera R, Visser O, Serraino D, Weiderpass E, Dei Tos AP, Ascoli V; RARECARE Working Group. Descriptive epidemiology of Kaposi sarcoma in Europe. Report from the RARECARE project. Cancer Epidemiol. 2014 Dec;38(6):670-8. doi: 10.1016/j.canep.2014.09.009. Epub 2014 Oct 22.</citation>
    <PMID>25454979</PMID>
  </reference>
  <reference>
    <citation>Tirabosco R, Mangham DC, Rosenberg AE, Vujovic S, Bousdras K, Pizzolitto S, De Maglio G, den Bakker MA, Di Francesco L, Kalil RK, Athanasou NA, O'Donnell P, McCarthy EF, Flanagan AM. Brachyury expression in extra-axial skeletal and soft tissue chordomas: a marker that distinguishes chordoma from mixed tumor/myoepithelioma/parachordoma in soft tissue. Am J Surg Pathol. 2008 Apr;32(4):572-80. doi: 10.1097/PAS.0b013e31815b693a.</citation>
    <PMID>18301055</PMID>
  </reference>
  <reference>
    <citation>Brien EW, Mirra JM, Ippolito V. Chondroblastoma arising from a nonepiphyseal site. Skeletal Radiol. 1995 Apr;24(3):220-2. doi: 10.1007/BF00228930.</citation>
    <PMID>7610417</PMID>
  </reference>
  <reference>
    <citation>Vujovic S, Henderson S, Presneau N, Odell E, Jacques TS, Tirabosco R, Boshoff C, Flanagan AM. Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas. J Pathol. 2006 Jun;209(2):157-65. doi: 10.1002/path.1969.</citation>
    <PMID>16538613</PMID>
  </reference>
  <reference>
    <citation>Miozzo M, Dalpra L, Riva P, Volonta M, Macciardi F, Pericotti S, Tibiletti MG, Cerati M, Rohde K, Larizza L, Fuhrman Conti AM. A tumor suppressor locus in familial and sporadic chordoma maps to 1p36. Int J Cancer. 2000 Jul 1;87(1):68-72.</citation>
    <PMID>10861454</PMID>
  </reference>
  <reference>
    <citation>Kelley MJ, Korczak JF, Sheridan E, Yang X, Goldstein AM, Parry DM. Familial chordoma, a tumor of notochordal remnants, is linked to chromosome 7q33. Am J Hum Genet. 2001 Aug;69(2):454-60. doi: 10.1086/321982. Epub 2001 Jul 10.</citation>
    <PMID>11452362</PMID>
  </reference>
  <reference>
    <citation>Lee-Jones L, Aligianis I, Davies PA, Puga A, Farndon PA, Stemmer-Rachamimov A, Ramesh V, Sampson JR. Sacrococcygeal chordomas in patients with tuberous sclerosis complex show somatic loss of TSC1 or TSC2. Genes Chromosomes Cancer. 2004 Sep;41(1):80-5. doi: 10.1002/gcc.20052.</citation>
    <PMID>15236319</PMID>
  </reference>
  <reference>
    <citation>Dutton RV, Singleton EB. Tuberous sclerosis: a case report with aortic aneurysm and unusual rib changes. Pediatr Radiol. 1975 Jun 13;3(3):184-6. doi: 10.1007/BF01006909.</citation>
    <PMID>1233436</PMID>
  </reference>
  <reference>
    <citation>Yang XR, Ng D, Alcorta DA, Liebsch NJ, Sheridan E, Li S, Goldstein AM, Parry DM, Kelley MJ. T (brachyury) gene duplication confers major susceptibility to familial chordoma. Nat Genet. 2009 Nov;41(11):1176-8. doi: 10.1038/ng.454. Epub 2009 Oct 4.</citation>
    <PMID>19801981</PMID>
  </reference>
  <reference>
    <citation>Schwab JH, Boland PJ, Agaram NP, Socci ND, Guo T, O'Toole GC, Wang X, Ostroumov E, Hunter CJ, Block JA, Doty S, Ferrone S, Healey JH, Antonescu CR. Chordoma and chondrosarcoma gene profile: implications for immunotherapy. Cancer Immunol Immunother. 2009 Mar;58(3):339-49. doi: 10.1007/s00262-008-0557-7. Epub 2008 Jul 19.</citation>
    <PMID>18641983</PMID>
  </reference>
  <reference>
    <citation>Oakley GJ, Fuhrer K, Seethala RR. Brachyury, SOX-9, and podoplanin, new markers in the skull base chordoma vs chondrosarcoma differential: a tissue microarray-based comparative analysis. Mod Pathol. 2008 Dec;21(12):1461-9. doi: 10.1038/modpathol.2008.144. Epub 2008 Sep 26.</citation>
    <PMID>18820665</PMID>
  </reference>
  <reference>
    <citation>Walcott BP, Nahed BV, Mohyeldin A, Coumans JV, Kahle KT, Ferreira MJ. Chordoma: current concepts, management, and future directions. Lancet Oncol. 2012 Feb;13(2):e69-76. doi: 10.1016/S1470-2045(11)70337-0.</citation>
    <PMID>22300861</PMID>
  </reference>
  <reference>
    <citation>Stacchiotti S, Sommer J; Chordoma Global Consensus Group. Building a global consensus approach to chordoma: a position paper from the medical and patient community. Lancet Oncol. 2015 Feb;16(2):e71-83. doi: 10.1016/S1470-2045(14)71190-8.</citation>
    <PMID>25638683</PMID>
  </reference>
  <reference>
    <citation>Dubory A, Missenard G, Lambert B, Court C. &quot;En bloc&quot; resection of sacral chordomas by combined anterior and posterior surgical approach: a monocentric retrospective review about 29 cases. Eur Spine J. 2014 Sep;23(9):1940-8. doi: 10.1007/s00586-014-3196-z. Epub 2014 Jan 28.</citation>
    <PMID>24469886</PMID>
  </reference>
  <reference>
    <citation>Asavamongkolkul A, Waikakul S. Wide resection of sacral chordoma via a posterior approach. Int Orthop. 2012 Mar;36(3):607-12. doi: 10.1007/s00264-011-1381-9. Epub 2011 Oct 29.</citation>
    <PMID>22038441</PMID>
  </reference>
  <reference>
    <citation>Stacchiotti S, Casali PG, Lo Vullo S, Mariani L, Palassini E, Mercuri M, Alberghini M, Pilotti S, Zanella L, Gronchi A, Picci P. Chordoma of the mobile spine and sacrum: a retrospective analysis of a series of patients surgically treated at two referral centers. Ann Surg Oncol. 2010 Jan;17(1):211-9. doi: 10.1245/s10434-009-0740-x. Epub 2009 Oct 22.</citation>
    <PMID>19847568</PMID>
  </reference>
  <reference>
    <citation>Varga PP, Szoverfi Z, Fisher CG, Boriani S, Gokaslan ZL, Dekutoski MB, Chou D, Quraishi NA, Reynolds JJ, Luzzati A, Williams R, Fehlings MG, Germscheid NM, Lazary A, Rhines LD. Surgical treatment of sacral chordoma: prognostic variables for local recurrence and overall survival. Eur Spine J. 2015 May;24(5):1092-101. doi: 10.1007/s00586-014-3728-6. Epub 2014 Dec 23.</citation>
    <PMID>25533857</PMID>
  </reference>
  <reference>
    <citation>Kayani B, Hanna SA, Sewell MD, Saifuddin A, Molloy S, Briggs TW. A review of the surgical management of sacral chordoma. Eur J Surg Oncol. 2014 Nov;40(11):1412-20. doi: 10.1016/j.ejso.2014.04.008. Epub 2014 Apr 25.</citation>
    <PMID>24793103</PMID>
  </reference>
  <reference>
    <citation>Puri A, Agarwal MG, Shah M, Srinivas CH, Shukla PJ, Shrikhande SV, Jambhekar NA. Decision making in primary sacral tumors. Spine J. 2009 May;9(5):396-403. doi: 10.1016/j.spinee.2008.10.001. Epub 2008 Dec 6.</citation>
    <PMID>19059810</PMID>
  </reference>
  <reference>
    <citation>Chen KW, Yang HL, Kandimalla Y, Liu JY, Wang GL. Review of current treatment of sacral chordoma. Orthop Surg. 2009 Aug;1(3):238-44. doi: 10.1111/j.1757-7861.2009.00027.x.</citation>
    <PMID>22009849</PMID>
  </reference>
  <reference>
    <citation>Gennari L, Azzarelli A, Quagliuolo V. A posterior approach for the excision of sacral chordoma. J Bone Joint Surg Br. 1987 Aug;69(4):565-8. doi: 10.1302/0301-620X.69B4.3611160.</citation>
    <PMID>3611160</PMID>
  </reference>
  <reference>
    <citation>Clarke MJ, Dasenbrock H, Bydon A, Sciubba DM, McGirt MJ, Hsieh PC, Yassari R, Gokaslan ZL, Wolinsky JP. Posterior-only approach for en bloc sacrectomy: clinical outcomes in 36 consecutive patients. Neurosurgery. 2012 Aug;71(2):357-64; discussion 364. doi: 10.1227/NEU.0b013e31825d01d4.</citation>
    <PMID>22569060</PMID>
  </reference>
  <reference>
    <citation>Weitao Y, Qiqing C, Songtao G, Jiaqiang W. Use of gluteus maximus adipomuscular sliding flaps in the reconstruction of sacral defects after tumor resection. World J Surg Oncol. 2013 May 23;11:110. doi: 10.1186/1477-7819-11-110.</citation>
    <PMID>23701700</PMID>
  </reference>
  <reference>
    <citation>Doita M, Harada T, Iguchi T, Sumi M, Sha H, Yoshiya S, Kurosaka M. Total sacrectomy and reconstruction for sacral tumors. Spine (Phila Pa 1976). 2003 Aug 1;28(15):E296-301. doi: 10.1097/01.BRS.0000083230.12704.E3.</citation>
    <PMID>12897508</PMID>
  </reference>
  <reference>
    <citation>Zhang HY, Thongtrangan I, Balabhadra RS, Murovic JA, Kim DH. Surgical techniques for total sacrectomy and spinopelvic reconstruction. Neurosurg Focus. 2003 Aug 15;15(2):E5. doi: 10.3171/foc.2003.15.2.5.</citation>
    <PMID>15350036</PMID>
  </reference>
  <reference>
    <citation>Kim JE, Pang J, Christensen JM, Coon D, Zadnik PL, Wolinsky JP, Gokaslan ZL, Bydon A, Sciubba DM, Witham T, Redett RJ, Sacks JM. Soft-tissue reconstruction after total en bloc sacrectomy. J Neurosurg Spine. 2015 Jun;22(6):571-81. doi: 10.3171/2014.10.SPINE14114. Epub 2015 Mar 27.</citation>
    <PMID>25815806</PMID>
  </reference>
  <reference>
    <citation>Maricevich M, Maricevich R, Chim H, Moran SL, Rose PS, Mardini S. Reconstruction following partial and total sacrectomy defects: an analysis of outcomes and complications. J Plast Reconstr Aesthet Surg. 2014 Sep;67(9):1257-66. doi: 10.1016/j.bjps.2014.05.001. Epub 2014 May 20.</citation>
    <PMID>24907194</PMID>
  </reference>
  <reference>
    <citation>Imai R, Kamada T, Sugahara S, Tsuji H, Tsujii H. Carbon ion radiotherapy for sacral chordoma. Br J Radiol. 2011 Dec;84 Spec No 1(Spec Iss 1):S48-54. doi: 10.1259/bjr/13783281. Epub 2011 Mar 22.</citation>
    <PMID>21427182</PMID>
  </reference>
  <reference>
    <citation>Yanagi T, Kamada T, Tsuji H, Imai R, Serizawa I, Tsujii H. Dose-volume histogram and dose-surface histogram analysis for skin reactions to carbon ion radiotherapy for bone and soft tissue sarcoma. Radiother Oncol. 2010 Apr;95(1):60-5. doi: 10.1016/j.radonc.2009.08.041. Epub 2009 Sep 18.</citation>
    <PMID>19767117</PMID>
  </reference>
  <reference>
    <citation>Mima M, Demizu Y, Jin D, Hashimoto N, Takagi M, Terashima K, Fujii O, Niwa Y, Akagi T, Daimon T, Hishikawa Y, Abe M, Murakami M, Sasaki R, Fuwa N. Particle therapy using carbon ions or protons as a definitive therapy for patients with primary sacral chordoma. Br J Radiol. 2014 Jan;87(1033):20130512. doi: 10.1259/bjr.20130512. Epub 2013 Nov 28.</citation>
    <PMID>24288399</PMID>
  </reference>
  <reference>
    <citation>Uhl M, Edler L, Jensen AD, Habl G, Oelmann J, Roder F, Jackel O, Debus J, Herfarth K. Randomized phase II trial of hypofractionated proton versus carbon ion radiation therapy in patients with sacrococcygeal chordoma-the ISAC trial protocol. Radiat Oncol. 2014 Apr 29;9:100. doi: 10.1186/1748-717X-9-100.</citation>
    <PMID>24774721</PMID>
  </reference>
  <reference>
    <citation>Fossati P, Molinelli S, Matsufuji N, Ciocca M, Mirandola A, Mairani A, Mizoe J, Hasegawa A, Imai R, Kamada T, Orecchia R, Tsujii H. Dose prescription in carbon ion radiotherapy: a planning study to compare NIRS and LEM approaches with a clinically-oriented strategy. Phys Med Biol. 2012 Nov 21;57(22):7543-54. doi: 10.1088/0031-9155/57/22/7543. Epub 2012 Oct 26.</citation>
    <PMID>23104051</PMID>
  </reference>
  <reference>
    <citation>Steinstrater O, Grun R, Scholz U, Friedrich T, Durante M, Scholz M. Mapping of RBE-weighted doses between HIMAC- and LEM-Based treatment planning systems for carbon ion therapy. Int J Radiat Oncol Biol Phys. 2012 Nov 1;84(3):854-60. doi: 10.1016/j.ijrobp.2012.01.038. Epub 2012 Apr 6.</citation>
    <PMID>22483698</PMID>
  </reference>
  <reference>
    <citation>DeLaney TF, Liebsch NJ, Pedlow FX, Adams J, Dean S, Yeap BY, McManus P, Rosenberg AE, Nielsen GP, Harmon DC, Spiro IJ, Raskin KA, Suit HD, Yoon SS, Hornicek FJ. Phase II study of high-dose photon/proton radiotherapy in the management of spine sarcomas. Int J Radiat Oncol Biol Phys. 2009 Jul 1;74(3):732-9. doi: 10.1016/j.ijrobp.2008.08.058. Epub 2008 Dec 25.</citation>
    <PMID>19095372</PMID>
  </reference>
  <reference>
    <citation>DeLaney TF, Liebsch NJ, Pedlow FX, Adams J, Weyman EA, Yeap BY, Depauw N, Nielsen GP, Harmon DC, Yoon SS, Chen YL, Schwab JH, Hornicek FJ. Long-term results of Phase II study of high dose photon/proton radiotherapy in the management of spine chordomas, chondrosarcomas, and other sarcomas. J Surg Oncol. 2014 Aug;110(2):115-22. doi: 10.1002/jso.23617. Epub 2014 Apr 19.</citation>
    <PMID>24752878</PMID>
  </reference>
  <reference>
    <citation>Chen YL, Liebsch N, Kobayashi W, Goldberg S, Kirsch D, Calkins G, Childs S, Schwab J, Hornicek F, DeLaney T. Definitive high-dose photon/proton radiotherapy for unresected mobile spine and sacral chordomas. Spine (Phila Pa 1976). 2013 Jul 1;38(15):E930-6. doi: 10.1097/BRS.0b013e318296e7d7.</citation>
    <PMID>23609202</PMID>
  </reference>
  <reference>
    <citation>Staab A, Rutz HP, Ares C, Timmermann B, Schneider R, Bolsi A, Albertini F, Lomax A, Goitein G, Hug E. Spot-scanning-based proton therapy for extracranial chordoma. Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):e489-96. doi: 10.1016/j.ijrobp.2011.02.018. Epub 2011 Apr 15.</citation>
    <PMID>21497457</PMID>
  </reference>
  <reference>
    <citation>Terezakis SA, Lovelock DM, Bilsky MH, Hunt MA, Zatcky J, Yamada Y. Image-guided intensity-modulated photon radiotherapy using multifractionated regimen to paraspinal chordomas and rare sarcomas. Int J Radiat Oncol Biol Phys. 2007 Dec 1;69(5):1502-8. doi: 10.1016/j.ijrobp.2007.05.019. Epub 2007 Aug 6.</citation>
    <PMID>17689028</PMID>
  </reference>
  <reference>
    <citation>Yamada Y, Laufer I, Cox BW, Lovelock DM, Maki RG, Zatcky JM, Boland PJ, Bilsky MH. Preliminary results of high-dose single-fraction radiotherapy for the management of chordomas of the spine and sacrum. Neurosurgery. 2013 Oct;73(4):673-80; discussion 680. doi: 10.1227/NEU.0000000000000083.</citation>
    <PMID>23842548</PMID>
  </reference>
  <reference>
    <citation>Zabel-du Bois A, Nikoghosyan A, Schwahofer A, Huber P, Schlegel W, Debus J, Milker-Zabel S. Intensity modulated radiotherapy in the management of sacral chordoma in primary versus recurrent disease. Radiother Oncol. 2010 Dec;97(3):408-12. doi: 10.1016/j.radonc.2010.10.008. Epub 2010 Nov 4.</citation>
    <PMID>21056488</PMID>
  </reference>
  <reference>
    <citation>Henderson FC, McCool K, Seigle J, Jean W, Harter W, Gagnon GJ. Treatment of chordomas with CyberKnife: georgetown university experience and treatment recommendations. Neurosurgery. 2009 Feb;64(2 Suppl):A44-53. doi: 10.1227/01.NEU.0000341166.09107.47.</citation>
    <PMID>19165073</PMID>
  </reference>
  <reference>
    <citation>Royston P, Parmar MK. The use of restricted mean survival time to estimate the treatment effect in randomized clinical trials when the proportional hazards assumption is in doubt. Stat Med. 2011 Aug 30;30(19):2409-21. doi: 10.1002/sim.4274. Epub 2011 May 25.</citation>
    <PMID>21611958</PMID>
  </reference>
  <reference>
    <citation>Stablein DM, Carter WH Jr, Novak JW. Analysis of survival data with nonproportional hazard functions. Control Clin Trials. 1981 Jun;2(2):149-59. doi: 10.1016/0197-2456(81)90005-2.</citation>
    <PMID>7273792</PMID>
  </reference>
  <reference>
    <citation>Li J, Scheike TH, Zhang MJ. Checking Fine and Gray subdistribution hazards model with cumulative sums of residuals. Lifetime Data Anal. 2015 Apr;21(2):197-217. doi: 10.1007/s10985-014-9313-9. Epub 2014 Nov 25.</citation>
    <PMID>25421251</PMID>
  </reference>
  <reference>
    <citation>McCandless LC, Gustafson P, Levy AR, Richardson S. Hierarchical priors for bias parameters in Bayesian sensitivity analysis for unmeasured confounding. Stat Med. 2012 Feb 20;31(4):383-96. doi: 10.1002/sim.4453.</citation>
    <PMID>22253142</PMID>
  </reference>
  <reference>
    <citation>Peduzzi P, Concato J, Feinstein AR, Holford TR. Importance of events per independent variable in proportional hazards regression analysis. II. Accuracy and precision of regression estimates. J Clin Epidemiol. 1995 Dec;48(12):1503-10. doi: 10.1016/0895-4356(95)00048-8.</citation>
    <PMID>8543964</PMID>
  </reference>
  <reference>
    <citation>Yuo TH, Degenholtz HS, Chaer RA, Kraemer KL, Makaroun MS. Effect of hospital-level variation in the use of carotid artery stenting versus carotid endarterectomy on perioperative stroke and death in asymptomatic patients. J Vasc Surg. 2013 Mar;57(3):627-34. doi: 10.1016/j.jvs.2012.09.036. Epub 2013 Jan 9.</citation>
    <PMID>23312937</PMID>
  </reference>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>December 2, 2016</study_first_submitted>
  <study_first_submitted_qc>December 5, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 8, 2016</study_first_posted>
  <last_update_submitted>September 12, 2023</last_update_submitted>
  <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Chordoma</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/NCT02986516
org study id: ISG SACRO
nct id: NCT02986516
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Comparative study on surgery versus definitive radiation therapy in primary localized sacral
      chordoma
International, multicenter, comparative, open-label, parallel-group, mixed
      Observational-Randomized Controlled Trial.

      All the patients, who are candidate for the study will receive full information on the
      characteristics, potential effectiveness and side effects of the two alternatives treatments:
      radiotherapy (RT) and surgical treatment Eligible patients will be asked to be randomized in
      order to receive treatment A (surgery, with or without RT) or treatment B (definitive RT) Who
      will refuse randomization will be included in the Prospective Cohort Study (PCS) and will be
      treated accordingly to their choice (treatment option A or treatment option B).

      The same radiotherapy and surgical regimen will be administered in the PCS and in the
      Randomized Clinical Trial (RCT) cohort
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Relapse Free Survival (RFS)
time frame: 5 years
description: The time from randomization or treatment start date to the date of local disease relapse, distant disease relapse, second primary malignancy or death from any cause, whichever occurred first.
measure: Overall Survival (OS)
time frame: The patients will be followed in term of Overall Survival, for all the study period (expected average: 10 years)
description: The time from randomization or treatment start date to the date of death from any cause
measure: Survival Post Progression (SPP)
time frame: Expected average: 36 months
description: The time from local disease relapse, distant disease relapse or second primary malignancy, whichever occurred first, to the date of death from any cause
measure: Local Relapse Failure (LRF)
time frame: Expected average: 60 months
description: The time from randomization or treatment start date to the date of local disease relapse
measure: Distant Relapse Failure (DRF)
time frame: Expected average: 60 months
description: The time from randomization or treatment start date to the date of distant disease relapse
measure: Best Response rate to definitive radiotherapy
time frame: At 12 months, 2 years and 5 years after radiotherapy
description: Best Response rate to definitive radiotherapy
measure: Time to best response rate to definitive radiotherapy
time frame: At 12 months, 2 years and 5 years after radiotherapy
description: Time to best response rate to definitive radiotherapy
measure: Adverse Events Incidence
time frame: At end of treatment , 6 months , 12 months 2 years and 5 years after surgery or radiotherapy
description: Adverse Events incidence
measure: Evaluation of quality of life measured with Functional Assessment of Cancer Therapy General
time frame: every 6 months (expected average: 5 years)
description: Evaluation of quality of life measured with Functional Assessment of Cancer Therapy General
measure: Evaluation of quality of life measured with Brief Inventory Pain questionnaires
time frame: every 6 months (expected average: 5 years)
description: Evaluation of quality of life measured with Brief Inventory Pain questionnaires
arm group label: Randomized Cohort
arm group type: Experimental
description: Participants who will decided to undergo to randomization, will receive surgical treatment or definitive radiotherapy according with randomization assignment
arm group label: Prospective Cohort
arm group type: Active Comparator
description: Participants who will not decide to be randomized, will received the surgical or definite radiotherapy treatment according to their choice
intervention type: Other
intervention name: Randomized Cohort
description: Surgical treatment with different approach, based on the characteristics of the tumor or definitive high dose radiotherapy (carbon ion radiotherapy, proton-therapy, mixed photons-proton therapy) will be assigned by randomization
arm group label: Randomized Cohort
intervention type: Radiation
intervention name: Prospective cohort
description: Surgical treatment or definitive high dose radiotherapy will be selected by the patients and will be prospectively evaluated
arm group label: Prospective Cohort
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Alessandro Gronchi, MD
role: Principal Investigator
affiliation: Istituto Nazionale Tumori Milan-Italy
last name: Piero Fossati, MD
role: Principal Investigator
affiliation: MedAustron Graz-Austria
last name: Alessandro Gronchi, MD
phone: +390223903714
email: alessandro.gronchi@istitutotumori.mi.it
last name: ISG Clinical Trial Center
email: clinicaltrials@italiansarcomagroup.org
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Active, not recruiting
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
country: Austria
country: Germany
country: Hungary
country: Italy
country: Japan
country: Netherlands
country: Norway
country: Poland
country: Spain
country: United Kingdom
citation: Stiller CA, Trama A, Brewster DH, Verne J, Bouchardy C, Navarro C, Chirlaque MD, Marcos-Gragera R, Visser O, Serraino D, Weiderpass E, Dei Tos AP, Ascoli V; RARECARE Working Group. Descriptive epidemiology of Kaposi sarcoma in Europe. Report from the RARECARE project. Cancer Epidemiol. 2014 Dec;38(6):670-8. doi: 10.1016/j.canep.2014.09.009. Epub 2014 Oct 22.
PMID: 25454979
citation: Tirabosco R, Mangham DC, Rosenberg AE, Vujovic S, Bousdras K, Pizzolitto S, De Maglio G, den Bakker MA, Di Francesco L, Kalil RK, Athanasou NA, O'Donnell P, McCarthy EF, Flanagan AM. Brachyury expression in extra-axial skeletal and soft tissue chordomas: a marker that distinguishes chordoma from mixed tumor/myoepithelioma/parachordoma in soft tissue. Am J Surg Pathol. 2008 Apr;32(4):572-80. doi: 10.1097/PAS.0b013e31815b693a.
PMID: 18301055
citation: Brien EW, Mirra JM, Ippolito V. Chondroblastoma arising from a nonepiphyseal site. Skeletal Radiol. 1995 Apr;24(3):220-2. doi: 10.1007/BF00228930.
PMID: 7610417
citation: Vujovic S, Henderson S, Presneau N, Odell E, Jacques TS, Tirabosco R, Boshoff C, Flanagan AM. Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas. J Pathol. 2006 Jun;209(2):157-65. doi: 10.1002/path.1969.
PMID: 16538613
citation: Miozzo M, Dalpra L, Riva P, Volonta M, Macciardi F, Pericotti S, Tibiletti MG, Cerati M, Rohde K, Larizza L, Fuhrman Conti AM. A tumor suppressor locus in familial and sporadic chordoma maps to 1p36. Int J Cancer. 2000 Jul 1;87(1):68-72.
PMID: 10861454
citation: Kelley MJ, Korczak JF, Sheridan E, Yang X, Goldstein AM, Parry DM. Familial chordoma, a tumor of notochordal remnants, is linked to chromosome 7q33. Am J Hum Genet. 2001 Aug;69(2):454-60. doi: 10.1086/321982. Epub 2001 Jul 10.
PMID: 11452362
citation: Lee-Jones L, Aligianis I, Davies PA, Puga A, Farndon PA, Stemmer-Rachamimov A, Ramesh V, Sampson JR. Sacrococcygeal chordomas in patients with tuberous sclerosis complex show somatic loss of TSC1 or TSC2. Genes Chromosomes Cancer. 2004 Sep;41(1):80-5. doi: 10.1002/gcc.20052.
PMID: 15236319
citation: Dutton RV, Singleton EB. Tuberous sclerosis: a case report with aortic aneurysm and unusual rib changes. Pediatr Radiol. 1975 Jun 13;3(3):184-6. doi: 10.1007/BF01006909.
PMID: 1233436
citation: Yang XR, Ng D, Alcorta DA, Liebsch NJ, Sheridan E, Li S, Goldstein AM, Parry DM, Kelley MJ. T (brachyury) gene duplication confers major susceptibility to familial chordoma. Nat Genet. 2009 Nov;41(11):1176-8. doi: 10.1038/ng.454. Epub 2009 Oct 4.
PMID: 19801981
citation: Schwab JH, Boland PJ, Agaram NP, Socci ND, Guo T, O'Toole GC, Wang X, Ostroumov E, Hunter CJ, Block JA, Doty S, Ferrone S, Healey JH, Antonescu CR. Chordoma and chondrosarcoma gene profile: implications for immunotherapy. Cancer Immunol Immunother. 2009 Mar;58(3):339-49. doi: 10.1007/s00262-008-0557-7. Epub 2008 Jul 19.
PMID: 18641983
citation: Oakley GJ, Fuhrer K, Seethala RR. Brachyury, SOX-9, and podoplanin, new markers in the skull base chordoma vs chondrosarcoma differential: a tissue microarray-based comparative analysis. Mod Pathol. 2008 Dec;21(12):1461-9. doi: 10.1038/modpathol.2008.144. Epub 2008 Sep 26.
PMID: 18820665
citation: Walcott BP, Nahed BV, Mohyeldin A, Coumans JV, Kahle KT, Ferreira MJ. Chordoma: current concepts, management, and future directions. Lancet Oncol. 2012 Feb;13(2):e69-76. doi: 10.1016/S1470-2045(11)70337-0.
PMID: 22300861
citation: Stacchiotti S, Sommer J; Chordoma Global Consensus Group. Building a global consensus approach to chordoma: a position paper from the medical and patient community. Lancet Oncol. 2015 Feb;16(2):e71-83. doi: 10.1016/S1470-2045(14)71190-8.
PMID: 25638683
citation: Dubory A, Missenard G, Lambert B, Court C. "En bloc" resection of sacral chordomas by combined anterior and posterior surgical approach: a monocentric retrospective review about 29 cases. Eur Spine J. 2014 Sep;23(9):1940-8. doi: 10.1007/s00586-014-3196-z. Epub 2014 Jan 28.
PMID: 24469886
citation: Asavamongkolkul A, Waikakul S. Wide resection of sacral chordoma via a posterior approach. Int Orthop. 2012 Mar;36(3):607-12. doi: 10.1007/s00264-011-1381-9. Epub 2011 Oct 29.
PMID: 22038441
citation: Stacchiotti S, Casali PG, Lo Vullo S, Mariani L, Palassini E, Mercuri M, Alberghini M, Pilotti S, Zanella L, Gronchi A, Picci P. Chordoma of the mobile spine and sacrum: a retrospective analysis of a series of patients surgically treated at two referral centers. Ann Surg Oncol. 2010 Jan;17(1):211-9. doi: 10.1245/s10434-009-0740-x. Epub 2009 Oct 22.
PMID: 19847568
citation: Varga PP, Szoverfi Z, Fisher CG, Boriani S, Gokaslan ZL, Dekutoski MB, Chou D, Quraishi NA, Reynolds JJ, Luzzati A, Williams R, Fehlings MG, Germscheid NM, Lazary A, Rhines LD. Surgical treatment of sacral chordoma: prognostic variables for local recurrence and overall survival. Eur Spine J. 2015 May;24(5):1092-101. doi: 10.1007/s00586-014-3728-6. Epub 2014 Dec 23.
PMID: 25533857
citation: Kayani B, Hanna SA, Sewell MD, Saifuddin A, Molloy S, Briggs TW. A review of the surgical management of sacral chordoma. Eur J Surg Oncol. 2014 Nov;40(11):1412-20. doi: 10.1016/j.ejso.2014.04.008. Epub 2014 Apr 25.
PMID: 24793103
citation: Puri A, Agarwal MG, Shah M, Srinivas CH, Shukla PJ, Shrikhande SV, Jambhekar NA. Decision making in primary sacral tumors. Spine J. 2009 May;9(5):396-403. doi: 10.1016/j.spinee.2008.10.001. Epub 2008 Dec 6.
PMID: 19059810
citation: Chen KW, Yang HL, Kandimalla Y, Liu JY, Wang GL. Review of current treatment of sacral chordoma. Orthop Surg. 2009 Aug;1(3):238-44. doi: 10.1111/j.1757-7861.2009.00027.x.
PMID: 22009849
citation: Gennari L, Azzarelli A, Quagliuolo V. A posterior approach for the excision of sacral chordoma. J Bone Joint Surg Br. 1987 Aug;69(4):565-8. doi: 10.1302/0301-620X.69B4.3611160.
PMID: 3611160
citation: Clarke MJ, Dasenbrock H, Bydon A, Sciubba DM, McGirt MJ, Hsieh PC, Yassari R, Gokaslan ZL, Wolinsky JP. Posterior-only approach for en bloc sacrectomy: clinical outcomes in 36 consecutive patients. Neurosurgery. 2012 Aug;71(2):357-64; discussion 364. doi: 10.1227/NEU.0b013e31825d01d4.
PMID: 22569060
citation: Weitao Y, Qiqing C, Songtao G, Jiaqiang W. Use of gluteus maximus adipomuscular sliding flaps in the reconstruction of sacral defects after tumor resection. World J Surg Oncol. 2013 May 23;11:110. doi: 10.1186/1477-7819-11-110.
PMID: 23701700
citation: Doita M, Harada T, Iguchi T, Sumi M, Sha H, Yoshiya S, Kurosaka M. Total sacrectomy and reconstruction for sacral tumors. Spine (Phila Pa 1976). 2003 Aug 1;28(15):E296-301. doi: 10.1097/01.BRS.0000083230.12704.E3.
PMID: 12897508
citation: Zhang HY, Thongtrangan I, Balabhadra RS, Murovic JA, Kim DH. Surgical techniques for total sacrectomy and spinopelvic reconstruction. Neurosurg Focus. 2003 Aug 15;15(2):E5. doi: 10.3171/foc.2003.15.2.5.
PMID: 15350036
citation: Kim JE, Pang J, Christensen JM, Coon D, Zadnik PL, Wolinsky JP, Gokaslan ZL, Bydon A, Sciubba DM, Witham T, Redett RJ, Sacks JM. Soft-tissue reconstruction after total en bloc sacrectomy. J Neurosurg Spine. 2015 Jun;22(6):571-81. doi: 10.3171/2014.10.SPINE14114. Epub 2015 Mar 27.
PMID: 25815806
citation: Maricevich M, Maricevich R, Chim H, Moran SL, Rose PS, Mardini S. Reconstruction following partial and total sacrectomy defects: an analysis of outcomes and complications. J Plast Reconstr Aesthet Surg. 2014 Sep;67(9):1257-66. doi: 10.1016/j.bjps.2014.05.001. Epub 2014 May 20.
PMID: 24907194
citation: Imai R, Kamada T, Sugahara S, Tsuji H, Tsujii H. Carbon ion radiotherapy for sacral chordoma. Br J Radiol. 2011 Dec;84 Spec No 1(Spec Iss 1):S48-54. doi: 10.1259/bjr/13783281. Epub 2011 Mar 22.
PMID: 21427182
citation: Yanagi T, Kamada T, Tsuji H, Imai R, Serizawa I, Tsujii H. Dose-volume histogram and dose-surface histogram analysis for skin reactions to carbon ion radiotherapy for bone and soft tissue sarcoma. Radiother Oncol. 2010 Apr;95(1):60-5. doi: 10.1016/j.radonc.2009.08.041. Epub 2009 Sep 18.
PMID: 19767117
citation: Mima M, Demizu Y, Jin D, Hashimoto N, Takagi M, Terashima K, Fujii O, Niwa Y, Akagi T, Daimon T, Hishikawa Y, Abe M, Murakami M, Sasaki R, Fuwa N. Particle therapy using carbon ions or protons as a definitive therapy for patients with primary sacral chordoma. Br J Radiol. 2014 Jan;87(1033):20130512. doi: 10.1259/bjr.20130512. Epub 2013 Nov 28.
PMID: 24288399
citation: Uhl M, Edler L, Jensen AD, Habl G, Oelmann J, Roder F, Jackel O, Debus J, Herfarth K. Randomized phase II trial of hypofractionated proton versus carbon ion radiation therapy in patients with sacrococcygeal chordoma-the ISAC trial protocol. Radiat Oncol. 2014 Apr 29;9:100. doi: 10.1186/1748-717X-9-100.
PMID: 24774721
citation: Fossati P, Molinelli S, Matsufuji N, Ciocca M, Mirandola A, Mairani A, Mizoe J, Hasegawa A, Imai R, Kamada T, Orecchia R, Tsujii H. Dose prescription in carbon ion radiotherapy: a planning study to compare NIRS and LEM approaches with a clinically-oriented strategy. Phys Med Biol. 2012 Nov 21;57(22):7543-54. doi: 10.1088/0031-9155/57/22/7543. Epub 2012 Oct 26.
PMID: 23104051
citation: Steinstrater O, Grun R, Scholz U, Friedrich T, Durante M, Scholz M. Mapping of RBE-weighted doses between HIMAC- and LEM-Based treatment planning systems for carbon ion therapy. Int J Radiat Oncol Biol Phys. 2012 Nov 1;84(3):854-60. doi: 10.1016/j.ijrobp.2012.01.038. Epub 2012 Apr 6.
PMID: 22483698
citation: DeLaney TF, Liebsch NJ, Pedlow FX, Adams J, Dean S, Yeap BY, McManus P, Rosenberg AE, Nielsen GP, Harmon DC, Spiro IJ, Raskin KA, Suit HD, Yoon SS, Hornicek FJ. Phase II study of high-dose photon/proton radiotherapy in the management of spine sarcomas. Int J Radiat Oncol Biol Phys. 2009 Jul 1;74(3):732-9. doi: 10.1016/j.ijrobp.2008.08.058. Epub 2008 Dec 25.
PMID: 19095372
citation: DeLaney TF, Liebsch NJ, Pedlow FX, Adams J, Weyman EA, Yeap BY, Depauw N, Nielsen GP, Harmon DC, Yoon SS, Chen YL, Schwab JH, Hornicek FJ. Long-term results of Phase II study of high dose photon/proton radiotherapy in the management of spine chordomas, chondrosarcomas, and other sarcomas. J Surg Oncol. 2014 Aug;110(2):115-22. doi: 10.1002/jso.23617. Epub 2014 Apr 19.
PMID: 24752878
citation: Chen YL, Liebsch N, Kobayashi W, Goldberg S, Kirsch D, Calkins G, Childs S, Schwab J, Hornicek F, DeLaney T. Definitive high-dose photon/proton radiotherapy for unresected mobile spine and sacral chordomas. Spine (Phila Pa 1976). 2013 Jul 1;38(15):E930-6. doi: 10.1097/BRS.0b013e318296e7d7.
PMID: 23609202
citation: Staab A, Rutz HP, Ares C, Timmermann B, Schneider R, Bolsi A, Albertini F, Lomax A, Goitein G, Hug E. Spot-scanning-based proton therapy for extracranial chordoma. Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):e489-96. doi: 10.1016/j.ijrobp.2011.02.018. Epub 2011 Apr 15.
PMID: 21497457
citation: Terezakis SA, Lovelock DM, Bilsky MH, Hunt MA, Zatcky J, Yamada Y. Image-guided intensity-modulated photon radiotherapy using multifractionated regimen to paraspinal chordomas and rare sarcomas. Int J Radiat Oncol Biol Phys. 2007 Dec 1;69(5):1502-8. doi: 10.1016/j.ijrobp.2007.05.019. Epub 2007 Aug 6.
PMID: 17689028
citation: Yamada Y, Laufer I, Cox BW, Lovelock DM, Maki RG, Zatcky JM, Boland PJ, Bilsky MH. Preliminary results of high-dose single-fraction radiotherapy for the management of chordomas of the spine and sacrum. Neurosurgery. 2013 Oct;73(4):673-80; discussion 680. doi: 10.1227/NEU.0000000000000083.
PMID: 23842548
citation: Zabel-du Bois A, Nikoghosyan A, Schwahofer A, Huber P, Schlegel W, Debus J, Milker-Zabel S. Intensity modulated radiotherapy in the management of sacral chordoma in primary versus recurrent disease. Radiother Oncol. 2010 Dec;97(3):408-12. doi: 10.1016/j.radonc.2010.10.008. Epub 2010 Nov 4.
PMID: 21056488
citation: Henderson FC, McCool K, Seigle J, Jean W, Harter W, Gagnon GJ. Treatment of chordomas with CyberKnife: georgetown university experience and treatment recommendations. Neurosurgery. 2009 Feb;64(2 Suppl):A44-53. doi: 10.1227/01.NEU.0000341166.09107.47.
PMID: 19165073
citation: Royston P, Parmar MK. The use of restricted mean survival time to estimate the treatment effect in randomized clinical trials when the proportional hazards assumption is in doubt. Stat Med. 2011 Aug 30;30(19):2409-21. doi: 10.1002/sim.4274. Epub 2011 May 25.
PMID: 21611958
citation: Stablein DM, Carter WH Jr, Novak JW. Analysis of survival data with nonproportional hazard functions. Control Clin Trials. 1981 Jun;2(2):149-59. doi: 10.1016/0197-2456(81)90005-2.
PMID: 7273792
citation: Li J, Scheike TH, Zhang MJ. Checking Fine and Gray subdistribution hazards model with cumulative sums of residuals. Lifetime Data Anal. 2015 Apr;21(2):197-217. doi: 10.1007/s10985-014-9313-9. Epub 2014 Nov 25.
PMID: 25421251
citation: McCandless LC, Gustafson P, Levy AR, Richardson S. Hierarchical priors for bias parameters in Bayesian sensitivity analysis for unmeasured confounding. Stat Med. 2012 Feb 20;31(4):383-96. doi: 10.1002/sim.4453.
PMID: 22253142
citation: Peduzzi P, Concato J, Feinstein AR, Holford TR. Importance of events per independent variable in proportional hazards regression analysis. II. Accuracy and precision of regression estimates. J Clin Epidemiol. 1995 Dec;48(12):1503-10. doi: 10.1016/0895-4356(95)00048-8.
PMID: 8543964
citation: Yuo TH, Degenholtz HS, Chaer RA, Kraemer KL, Makaroun MS. Effect of hospital-level variation in the use of carotid artery stenting versus carotid endarterectomy on perioperative stroke and death in asymptomatic patients. J Vasc Surg. 2013 Mar;57(3):627-34. doi: 10.1016/j.jvs.2012.09.036. Epub 2013 Jan 9.
PMID: 23312937
responsible party type: Sponsor
mesh term: Chordoma
sharing ipd: No