<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/NCT02189473</url>
  </required_header>
  <id_info>
    <org_study_id>ARO 200901</org_study_id>
    <nct_id>NCT02189473</nct_id>
  </id_info>
  <brief_title>Radiotherapy of Motor Deficits From Metastatic Epidural Spinal Cord Compression</brief_title>
  <acronym>SCORE-2</acronym>
  <official_title>Radiotherapy of Motor Deficits From Metastatic Epidural Spinal Cord Compression (10 x 3 Gy Versus 5 x 4 Gy)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Prof. Dirk Rades, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital Schleswig-Holstein</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary aim of this randomized multi-center trial is to investigate the efficacy of the&#xD;
      radiotherapy regimens 5 x 4 Gy and 10 x 3 Gy with respect to the effect on motor function in&#xD;
      patients with metastatic epidural spinal cord compression.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary aim of this randomized multi-center trial is to investigate the efficacy of the&#xD;
      radiotherapy regimens 5 x 4 Gy and 10 x 3 Gy with respect to the effect on motor function in&#xD;
      patients with metastatic epidural spinal cord compression. The response rate (improvement in&#xD;
      motor function or prevention of progression) will be assessed at one month following&#xD;
      radiotherapy.&#xD;
&#xD;
      In addition, the following endpoints will be evaluated:&#xD;
&#xD;
        1. Motor function; additional assessments directly and at 3 and at 6 months after&#xD;
           radiotherapy&#xD;
&#xD;
        2. Ability to walk; assessment directly and at 1, 3 and 6 months after radiotherapy&#xD;
&#xD;
        3. Sensory function; assessment directly and at 1, 3 and 6 months after radiotherapy&#xD;
&#xD;
        4. Quality of life; evaluation directly and at 1, 3 and 6 months after radiotherapy&#xD;
&#xD;
        5. Pain assessment directly and at 1, 3 and 6 months after radiotherapy&#xD;
&#xD;
        6. Overall survival up to 6 months following radiotherapy&#xD;
&#xD;
        7. Local Progression-free survival up to 6 months following radiotherapy&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2010</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</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>Number of Participants Showing Improvement or no Further Progression of Motor Deficits at 1 Month Following Radiotherapy</measure>
    <time_frame>at 1 month following radiotherapy</time_frame>
    <description>Overall response was defined as improvement or no further progression of motor deficits following radiotherapy.&#xD;
Motor function was graded with the following 8-point scale: 0, complete paraplegia; 1, palpable or visible muscle contractions; 2, active movement of the leg without gravity; 3, active movement against gravity; 4, active movement against mild resistance; 5, active movement against intermediate resistance; 6, active movement against strong resistance; and 7, normal strength.&#xD;
Motor function was recorded separately for each leg resulting in total points of 0 to 14. Improvement of motor function was defined as an increase by at least 2 points compared to baseline. No further progression was defined as +/-1 point (i.e. +1 point, +/- 0 points or -1 point).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Were Able to Walk at 1 Month Following Radiotherapy</measure>
    <time_frame>at 1 month following radiotherapy</time_frame>
    <description>Ambulatory status was assessed using the following scoring system:&#xD;
0 = Normal strength&#xD;
= Ambulatory without aid&#xD;
= Ambulatory with aid&#xD;
= Not ambulatory&#xD;
A patient with a score equal to or less than 2 is considered &quot;able to walk&quot;. Both participants that could and could not walk prior to radiotherapy have been included in this assessment..</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Were Alive at 6 Months Following Radiotherapy Without Deterioration of Motor Function During (or Directly Following) Radiotherapy and Freedom From In-field Recurrence of Metastatic Spinal Cord Compression Following Radiotherapy</measure>
    <time_frame>6 months following radiotherapy</time_frame>
    <description>Local Progression Free Survival (LPFS) was defined as freedom from progression of motor deficits during or one month following radiotherapy and freedom from in-field recurrence of metastatic spinal cord compression (MSCC) following radiotherapy.&#xD;
An in-field recurrence was defined as a recurrence of MSCC associated with motor deficits in the region of the spinal cord that had been previously irradiated for MSCC.&#xD;
In case of clinical suspicion of sich a recurrence, a spinal MRI was performed to confirm the diagnosis. Time to in-field recurrence was calculated from the last day of radiotherapy, and the patients were followed for a maximum of 6 months after the end of radiotherapy. The values of 6-month LPFS were estimated using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Experienced Relief of Distress at 1 Month Following Radiotherapy Compared to Baseline</measure>
    <time_frame>at 1 month following radiotherapy</time_frame>
    <description>Distress (as an indicator of impairment of quality of life) was measured with the distress-thermometer. the patients rated their level of distress on a scale ranging from 0 (no distress) to 10 (extreme distress). Patients rated the distress they experienced during the last week and stated the reasons for distress from a list of items.&#xD;
An improvement (lower score) by 2 points was considered a clinically relevant relief of distress. Patients with baseline-scores of 0-1 points were not included, since improvement by 2 points was not possible.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Experienced Relief of Pain at 1 Month Following Radiotherapy Compared to Baseline</measure>
    <time_frame>at 1 month following radiotherapy</time_frame>
    <description>Pain was measured with a numeric self-rating scale ranging from 0 (no pain) to 10 (worst pain).&#xD;
Relief of pain was defined as improvement (=decrease of pain) by at least 2 points without increase of analgesics. Patients with baseline-scores of 0-1 points were not included, since improvement by 2 points was not possible.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Were Alive at 6 Months Following Radiotherapy</measure>
    <time_frame>6 months following radiotherapy</time_frame>
    <description>Overall Survival (OS) was defined as freedom from death of any cause.&#xD;
Time to death was calculated from the last day of radiotherapy, and the patients were followed for a maximum of 6 months after the end of radiotherapy. The values of 6-month OS were estimated using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Showing Improvement of Motor Deficits at 1 Month Following Radiotherapy</measure>
    <time_frame>at 1 month following radiotherapy</time_frame>
    <description>Motor function was graded with the following 8-point scale: 0, complete paraplegia; 1, palpable or visible muscle contractions; 2, active movement of the leg without gravity; 3, active movement against gravity; 4, active movement against mild resistance; 5, active movement against intermediate resistance; 6, active movement against strong resistance; and 7, normal strength.&#xD;
Motor function was recorded separately for each leg resulting in total points of 0 to 14. Improvement of motor function was defined as an increase by at least 2 points compared to baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Experiencing at Least One Grade &gt;=2 Radiotherapy-related Toxicity</measure>
    <time_frame>during radiotherapy and up to 6 months following radiotherapy</time_frame>
    <description>Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) (version 4)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">203</enrollment>
  <condition>Metastatic Epidural Spinal Cord Compression</condition>
  <arm_group>
    <arm_group_label>5 x 4 Gy in 1 week</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>radiotherapy with 5 x 4 Gy in 1 week (5 x 4 Gy per week)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>10 x 3 Gy in 2 weeks</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>radiotherapy with 10 x 3 Gy in 2 weeks (5 x 3 Gy per week)</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>radiotherapy</intervention_name>
    <description>external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
    <arm_group_label>10 x 3 Gy in 2 weeks</arm_group_label>
    <arm_group_label>5 x 4 Gy in 1 week</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Motor deficits of the lower extremities resulting from metastatic epidural spinal cord&#xD;
             compression, which have persisted for no longer than 30 days&#xD;
&#xD;
          -  Confirmation of diagnosis by magnetic resonance imaging (spinal computed tomography&#xD;
             allowed)&#xD;
&#xD;
          -  Relatively poor survival prognosis (defined as ≤35 points on the survival score&#xD;
             published in Cancer 2008)&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior radiotherapy or surgery of the spinal areas affected by MESCC&#xD;
&#xD;
          -  History of symptomatic brain tumor or symptomatic brain metastases&#xD;
&#xD;
          -  Metastases of the cervical spine only&#xD;
&#xD;
          -  Other severe neurological disorders&#xD;
&#xD;
          -  Pregnancy, Lactation&#xD;
&#xD;
          -  Indication for decompressive surgery + stabilization of the affected spinal areas&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>89 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dirk Rades, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Department of Radiation Oncology, University of Lübeck, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oberschwabenklinik Ravensburg</name>
      <address>
        <city>Ravensburg</city>
        <state>Baden-Wutemberg</state>
        <zip>88191</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Bayreuth</name>
      <address>
        <city>Bayreuth</city>
        <state>Bavaria</state>
        <zip>95445</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Regensburg</name>
      <address>
        <city>Regensburg</city>
        <state>Bavaria</state>
        <zip>93053</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Würzburg</name>
      <address>
        <city>Würzburg</city>
        <state>Bavaria</state>
        <zip>97080</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ruhr University</name>
      <address>
        <city>Bochum</city>
        <state>North Rhine Westphalia</state>
        <zip>44801</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radiotherapy Practice Dresden-Friedrichstadt</name>
      <address>
        <city>Dresden</city>
        <state>Saxonia</state>
        <zip>01067</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Lübeck</name>
      <address>
        <city>Lübeck</city>
        <state>Schleswig-Holstein</state>
        <zip>23538</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charite Berlin</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center of Radiotherapy and Radiation Oncology</name>
      <address>
        <city>Bremen</city>
        <zip>28239</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute of Oncology, Vilnius University</name>
      <address>
        <city>Vilnius</city>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saad Specialist Hospital</name>
      <address>
        <city>Khobar</city>
        <country>Saudi Arabia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute of Oncology</name>
      <address>
        <city>Ljubljana</city>
        <country>Slovenia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Consorcio Hospitalario Provencial de Castellon</name>
      <address>
        <city>Valencia</city>
        <state>Castellon</state>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cruces University Hospital</name>
      <address>
        <city>Barakaldo</city>
        <state>Vizcaya (Basque Country)</state>
        <zip>48903</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Lithuania</country>
    <country>Saudi Arabia</country>
    <country>Slovenia</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Maranzano E, Latini P. Effectiveness of radiation therapy without surgery in metastatic spinal cord compression: final results from a prospective trial. Int J Radiat Oncol Biol Phys. 1995 Jul 15;32(4):959-67. doi: 10.1016/0360-3016(95)00572-g.</citation>
    <PMID>7607970</PMID>
  </reference>
  <reference>
    <citation>Sorensen S, Borgesen SE, Rohde K, Rasmusson B, Bach F, Boge-Rasmussen T, Stjernholm P, Larsen BH, Agerlin N, Gjerris F, et al. Metastatic epidural spinal cord compression. Results of treatment and survival. Cancer. 1990 Apr 1;65(7):1502-8. doi: 10.1002/1097-0142(19900401)65:73.0.co;2-d.</citation>
    <PMID>2311062</PMID>
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  <reference>
    <citation>Helweg-Larsen S, Sorensen PS, Kreiner S. Prognostic factors in metastatic spinal cord compression: a prospective study using multivariate analysis of variables influencing survival and gait function in 153 patients. Int J Radiat Oncol Biol Phys. 2000 Mar 15;46(5):1163-9. doi: 10.1016/s0360-3016(99)00333-8.</citation>
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  <reference>
    <citation>Leviov M, Dale J, Stein M, Ben-Shahar M, Ben-Arush M, Milstein D, Goldsher D, Kuten A. The management of metastatic spinal cord compression: a radiotherapeutic success ceiling. Int J Radiat Oncol Biol Phys. 1993 Sep 30;27(2):231-4. doi: 10.1016/0360-3016(93)90232-k.</citation>
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  </reference>
  <reference>
    <citation>Rades D, Blach M, Bremer M, Wildfang I, Karstens JH, Heidenreich F. Prognostic significance of the time of developing motor deficits before radiation therapy in metastatic spinal cord compression: one-year results of a prospective trial. Int J Radiat Oncol Biol Phys. 2000 Dec 1;48(5):1403-8. doi: 10.1016/s0360-3016(00)01408-5.</citation>
    <PMID>11121640</PMID>
  </reference>
  <reference>
    <citation>Rades D, Heidenreich F, Bremer M, Karstens JH. Time of developing motor deficits before radiotherapy as a new and relevant prognostic factor in metastatic spinal cord compression: final results of a retrospective analysis. Eur Neurol. 2001;45(4):266-9. doi: 10.1159/000052141.</citation>
    <PMID>11385267</PMID>
  </reference>
  <reference>
    <citation>Rades D, Heidenreich F, Karstens JH. Final results of a prospective study of the prognostic value of the time to develop motor deficits before irradiation in metastatic spinal cord compression. Int J Radiat Oncol Biol Phys. 2002 Jul 15;53(4):975-9. doi: 10.1016/s0360-3016(02)02819-5.</citation>
    <PMID>12095565</PMID>
  </reference>
  <reference>
    <citation>Arcangeli G, Giovinazzo G, Saracino B, D'Angelo L, Giannarelli D, Arcangeli G, Micheli A. Radiation therapy in the management of symptomatic bone metastases: the effect of total dose and histology on pain relief and response duration. Int J Radiat Oncol Biol Phys. 1998 Dec 1;42(5):1119-26. doi: 10.1016/s0360-3016(98)00264-8.</citation>
    <PMID>9869238</PMID>
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    <citation>Niewald M, Tkocz HJ, Abel U, Scheib T, Walter K, Nieder C, Schnabel K, Berberich W, Kubale R, Fuchs M. Rapid course radiation therapy vs. more standard treatment: a randomized trial for bone metastases. Int J Radiat Oncol Biol Phys. 1996 Dec 1;36(5):1085-9. doi: 10.1016/s0360-3016(96)00388-4.</citation>
    <PMID>8985030</PMID>
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  <reference>
    <citation>8 Gy single fraction radiotherapy for the treatment of metastatic skeletal pain: randomised comparison with a multifraction schedule over 12 months of patient follow-up. Bone Pain Trial Working Party. Radiother Oncol. 1999 Aug;52(2):111-21.</citation>
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  <reference>
    <citation>Steenland E, Leer JW, van Houwelingen H, Post WJ, van den Hout WB, Kievit J, de Haes H, Martijn H, Oei B, Vonk E, van der Steen-Banasik E, Wiggenraad RG, Hoogenhout J, Warlam-Rodenhuis C, van Tienhoven G, Wanders R, Pomp J, van Reijn M, van Mierlo I, Rutten E. The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study. Radiother Oncol. 1999 Aug;52(2):101-9. doi: 10.1016/s0167-8140(99)00110-3. Erratum In: Radiother Oncol 1999 Nov;53(2):167. Leer, J [corrected to Leer, JW]; van Mierlo ,T [corrected to van Mierlo, I].</citation>
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    <citation>Rades D, Stalpers LJ, Veninga T, Schulte R, Hoskin PJ, Obralic N, Bajrovic A, Rudat V, Schwarz R, Hulshof MC, Poortmans P, Schild SE. Evaluation of five radiation schedules and prognostic factors for metastatic spinal cord compression. J Clin Oncol. 2005 May 20;23(15):3366-75. doi: 10.1200/JCO.2005.04.754.</citation>
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    <citation>Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, Shank B, Solin LJ, Wesson M. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991 May 15;21(1):109-22. doi: 10.1016/0360-3016(91)90171-y.</citation>
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    <citation>Barendsen GW. Dose fractionation, dose rate and iso-effect relationships for normal tissue responses. Int J Radiat Oncol Biol Phys. 1982 Nov;8(11):1981-97. doi: 10.1016/0360-3016(82)90459-x. No abstract available.</citation>
    <PMID>6759484</PMID>
  </reference>
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    <citation>Koswig S, Budach V. [Remineralization and pain relief in bone metastases after after different radiotherapy fractions (10 times 3 Gy vs. 1 time 8 Gy). A prospective study]. Strahlenther Onkol. 1999 Oct;175(10):500-8. doi: 10.1007/s000660050061. German.</citation>
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    <citation>Rades D, Dunst J, Schild SE. The first score predicting overall survival in patients with metastatic spinal cord compression. Cancer. 2008 Jan 1;112(1):157-61. doi: 10.1002/cncr.23150.</citation>
    <PMID>17948910</PMID>
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    <citation>Tomita T, Galicich JH, Sundaresan N. Radiation therapy for spinal epidural metastases with complete block. Acta Radiol Oncol. 1983;22(2):135-43. doi: 10.3109/02841868309134353.</citation>
    <PMID>6310968</PMID>
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    <citation>Maranzano E, Bellavita R, Rossi R, De Angelis V, Frattegiani A, Bagnoli R, Mignogna M, Beneventi S, Lupattelli M, Ponticelli P, Biti GP, Latini P. Short-course versus split-course radiotherapy in metastatic spinal cord compression: results of a phase III, randomized, multicenter trial. J Clin Oncol. 2005 May 20;23(15):3358-65. doi: 10.1200/JCO.2005.08.193. Epub 2005 Feb 28.</citation>
    <PMID>15738534</PMID>
  </reference>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>July 7, 2014</study_first_submitted>
  <study_first_submitted_qc>July 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 14, 2014</study_first_posted>
  <results_first_submitted>March 18, 2019</results_first_submitted>
  <results_first_submitted_qc>February 3, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">February 17, 2020</results_first_posted>
  <last_update_submitted>February 18, 2020</last_update_submitted>
  <last_update_submitted_qc>February 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital Schleswig-Holstein</investigator_affiliation>
    <investigator_full_name>Prof. Dirk Rades, MD</investigator_full_name>
    <investigator_title>Prof. Dr. Dirk Rades. MD</investigator_title>
  </responsible_party>
  <keyword>metastatic epidural spinal cord compression</keyword>
  <keyword>motor function</keyword>
  <keyword>ambulatory status</keyword>
  <keyword>pain</keyword>
  <keyword>quality of life</keyword>
  <keyword>overall survival</keyword>
  <keyword>local control</keyword>
  <keyword>toxicity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spinal Cord Compression</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>5 x 4 Gy in 1 Week</title>
          <description>radiotherapy with 5 x 4 Gy in 1 week (5 x 4 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
        </group>
        <group group_id="P2">
          <title>10 x 3 Gy in 2 Weeks</title>
          <description>radiotherapy with 10 x 3 Gy in 2 weeks (5 x 3 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="101"/>
                <participants group_id="P2" count="102"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="78"/>
                <participants group_id="P2" count="77"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="25"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>5 x 4 Gy in 1 Week</title>
          <description>radiotherapy with 5 x 4 Gy in 1 week (5 x 4 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
        </group>
        <group group_id="B2">
          <title>10 x 3 Gy in 2 Weeks</title>
          <description>radiotherapy with 10 x 3 Gy in 2 weeks (5 x 3 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="101"/>
            <count group_id="B2" value="102"/>
            <count group_id="B3" value="203"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="73"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="62"/>
                    <measurement group_id="B2" value="67"/>
                    <measurement group_id="B3" value="129"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="79"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="60"/>
                    <measurement group_id="B2" value="64"/>
                    <measurement group_id="B3" value="124"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Slovenia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lithuania</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Germany</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="75"/>
                    <measurement group_id="B2" value="89"/>
                    <measurement group_id="B3" value="164"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Showing Improvement or no Further Progression of Motor Deficits at 1 Month Following Radiotherapy</title>
        <description>Overall response was defined as improvement or no further progression of motor deficits following radiotherapy.&#xD;
Motor function was graded with the following 8-point scale: 0, complete paraplegia; 1, palpable or visible muscle contractions; 2, active movement of the leg without gravity; 3, active movement against gravity; 4, active movement against mild resistance; 5, active movement against intermediate resistance; 6, active movement against strong resistance; and 7, normal strength.&#xD;
Motor function was recorded separately for each leg resulting in total points of 0 to 14. Improvement of motor function was defined as an increase by at least 2 points compared to baseline. No further progression was defined as +/-1 point (i.e. +1 point, +/- 0 points or -1 point).</description>
        <time_frame>at 1 month following radiotherapy</time_frame>
        <group_list>
          <group group_id="O1">
            <title>5 x 4 Gy in 1 Week</title>
            <description>radiotherapy with 5 x 4 Gy in 1 week (5 x 4 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
          </group>
          <group group_id="O2">
            <title>10 x 3 Gy in 2 Weeks</title>
            <description>radiotherapy with 10 x 3 Gy in 2 weeks (5 x 3 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Showing Improvement or no Further Progression of Motor Deficits at 1 Month Following Radiotherapy</title>
          <description>Overall response was defined as improvement or no further progression of motor deficits following radiotherapy.&#xD;
Motor function was graded with the following 8-point scale: 0, complete paraplegia; 1, palpable or visible muscle contractions; 2, active movement of the leg without gravity; 3, active movement against gravity; 4, active movement against mild resistance; 5, active movement against intermediate resistance; 6, active movement against strong resistance; and 7, normal strength.&#xD;
Motor function was recorded separately for each leg resulting in total points of 0 to 14. Improvement of motor function was defined as an increase by at least 2 points compared to baseline. No further progression was defined as +/-1 point (i.e. +1 point, +/- 0 points or -1 point).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="78"/>
                <count group_id="O2" value="77"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68"/>
                    <measurement group_id="O2" value="69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Were Able to Walk at 1 Month Following Radiotherapy</title>
        <description>Ambulatory status was assessed using the following scoring system:&#xD;
0 = Normal strength&#xD;
= Ambulatory without aid&#xD;
= Ambulatory with aid&#xD;
= Not ambulatory&#xD;
A patient with a score equal to or less than 2 is considered &quot;able to walk&quot;. Both participants that could and could not walk prior to radiotherapy have been included in this assessment..</description>
        <time_frame>at 1 month following radiotherapy</time_frame>
        <group_list>
          <group group_id="O1">
            <title>5 x 4 Gy in 1 Week</title>
            <description>radiotherapy with 5 x 4 Gy in 1 week (5 x 4 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
          </group>
          <group group_id="O2">
            <title>10 x 3 Gy in 2 Weeks</title>
            <description>radiotherapy with 10 x 3 Gy in 2 weeks (5 x 3 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Were Able to Walk at 1 Month Following Radiotherapy</title>
          <description>Ambulatory status was assessed using the following scoring system:&#xD;
0 = Normal strength&#xD;
= Ambulatory without aid&#xD;
= Ambulatory with aid&#xD;
= Not ambulatory&#xD;
A patient with a score equal to or less than 2 is considered &quot;able to walk&quot;. Both participants that could and could not walk prior to radiotherapy have been included in this assessment..</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="78"/>
                <count group_id="O2" value="77"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56"/>
                    <measurement group_id="O2" value="57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Were Alive at 6 Months Following Radiotherapy Without Deterioration of Motor Function During (or Directly Following) Radiotherapy and Freedom From In-field Recurrence of Metastatic Spinal Cord Compression Following Radiotherapy</title>
        <description>Local Progression Free Survival (LPFS) was defined as freedom from progression of motor deficits during or one month following radiotherapy and freedom from in-field recurrence of metastatic spinal cord compression (MSCC) following radiotherapy.&#xD;
An in-field recurrence was defined as a recurrence of MSCC associated with motor deficits in the region of the spinal cord that had been previously irradiated for MSCC.&#xD;
In case of clinical suspicion of sich a recurrence, a spinal MRI was performed to confirm the diagnosis. Time to in-field recurrence was calculated from the last day of radiotherapy, and the patients were followed for a maximum of 6 months after the end of radiotherapy. The values of 6-month LPFS were estimated using the Kaplan-Meier method.</description>
        <time_frame>6 months following radiotherapy</time_frame>
        <group_list>
          <group group_id="O1">
            <title>5 x 4 Gy in 1 Week</title>
            <description>radiotherapy with 5 x 4 Gy in 1 week (5 x 4 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
          </group>
          <group group_id="O2">
            <title>10 x 3 Gy in 2 Weeks</title>
            <description>radiotherapy with 10 x 3 Gy in 2 weeks (5 x 3 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Were Alive at 6 Months Following Radiotherapy Without Deterioration of Motor Function During (or Directly Following) Radiotherapy and Freedom From In-field Recurrence of Metastatic Spinal Cord Compression Following Radiotherapy</title>
          <description>Local Progression Free Survival (LPFS) was defined as freedom from progression of motor deficits during or one month following radiotherapy and freedom from in-field recurrence of metastatic spinal cord compression (MSCC) following radiotherapy.&#xD;
An in-field recurrence was defined as a recurrence of MSCC associated with motor deficits in the region of the spinal cord that had been previously irradiated for MSCC.&#xD;
In case of clinical suspicion of sich a recurrence, a spinal MRI was performed to confirm the diagnosis. Time to in-field recurrence was calculated from the last day of radiotherapy, and the patients were followed for a maximum of 6 months after the end of radiotherapy. The values of 6-month LPFS were estimated using the Kaplan-Meier method.</description>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
                <count group_id="O2" value="102"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="75.2"/>
                    <measurement group_id="O2" value="81.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Experienced Relief of Distress at 1 Month Following Radiotherapy Compared to Baseline</title>
        <description>Distress (as an indicator of impairment of quality of life) was measured with the distress-thermometer. the patients rated their level of distress on a scale ranging from 0 (no distress) to 10 (extreme distress). Patients rated the distress they experienced during the last week and stated the reasons for distress from a list of items.&#xD;
An improvement (lower score) by 2 points was considered a clinically relevant relief of distress. Patients with baseline-scores of 0-1 points were not included, since improvement by 2 points was not possible.</description>
        <time_frame>at 1 month following radiotherapy</time_frame>
        <group_list>
          <group group_id="O1">
            <title>5 x 4 Gy in 1 Week</title>
            <description>radiotherapy with 5 x 4 Gy in 1 week (5 x 4 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
          </group>
          <group group_id="O2">
            <title>10 x 3 Gy in 2 Weeks</title>
            <description>radiotherapy with 10 x 3 Gy in 2 weeks (5 x 3 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Experienced Relief of Distress at 1 Month Following Radiotherapy Compared to Baseline</title>
          <description>Distress (as an indicator of impairment of quality of life) was measured with the distress-thermometer. the patients rated their level of distress on a scale ranging from 0 (no distress) to 10 (extreme distress). Patients rated the distress they experienced during the last week and stated the reasons for distress from a list of items.&#xD;
An improvement (lower score) by 2 points was considered a clinically relevant relief of distress. Patients with baseline-scores of 0-1 points were not included, since improvement by 2 points was not possible.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="74"/>
                <count group_id="O2" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43"/>
                    <measurement group_id="O2" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Experienced Relief of Pain at 1 Month Following Radiotherapy Compared to Baseline</title>
        <description>Pain was measured with a numeric self-rating scale ranging from 0 (no pain) to 10 (worst pain).&#xD;
Relief of pain was defined as improvement (=decrease of pain) by at least 2 points without increase of analgesics. Patients with baseline-scores of 0-1 points were not included, since improvement by 2 points was not possible.</description>
        <time_frame>at 1 month following radiotherapy</time_frame>
        <group_list>
          <group group_id="O1">
            <title>5 x 4 Gy in 1 Week</title>
            <description>radiotherapy with 5 x 4 Gy in 1 week (5 x 4 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
          </group>
          <group group_id="O2">
            <title>10 x 3 Gy in 2 Weeks</title>
            <description>radiotherapy with 10 x 3 Gy in 2 weeks (5 x 3 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Experienced Relief of Pain at 1 Month Following Radiotherapy Compared to Baseline</title>
          <description>Pain was measured with a numeric self-rating scale ranging from 0 (no pain) to 10 (worst pain).&#xD;
Relief of pain was defined as improvement (=decrease of pain) by at least 2 points without increase of analgesics. Patients with baseline-scores of 0-1 points were not included, since improvement by 2 points was not possible.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="70"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36"/>
                    <measurement group_id="O2" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Were Alive at 6 Months Following Radiotherapy</title>
        <description>Overall Survival (OS) was defined as freedom from death of any cause.&#xD;
Time to death was calculated from the last day of radiotherapy, and the patients were followed for a maximum of 6 months after the end of radiotherapy. The values of 6-month OS were estimated using the Kaplan-Meier method.</description>
        <time_frame>6 months following radiotherapy</time_frame>
        <group_list>
          <group group_id="O1">
            <title>5 x 4 Gy in 1 Week</title>
            <description>radiotherapy with 5 x 4 Gy in 1 week (5 x 4 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
          </group>
          <group group_id="O2">
            <title>10 x 3 Gy in 2 Weeks</title>
            <description>radiotherapy with 10 x 3 Gy in 2 weeks (5 x 3 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Were Alive at 6 Months Following Radiotherapy</title>
          <description>Overall Survival (OS) was defined as freedom from death of any cause.&#xD;
Time to death was calculated from the last day of radiotherapy, and the patients were followed for a maximum of 6 months after the end of radiotherapy. The values of 6-month OS were estimated using the Kaplan-Meier method.</description>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
                <count group_id="O2" value="102"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.3"/>
                    <measurement group_id="O2" value="37.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Showing Improvement of Motor Deficits at 1 Month Following Radiotherapy</title>
        <description>Motor function was graded with the following 8-point scale: 0, complete paraplegia; 1, palpable or visible muscle contractions; 2, active movement of the leg without gravity; 3, active movement against gravity; 4, active movement against mild resistance; 5, active movement against intermediate resistance; 6, active movement against strong resistance; and 7, normal strength.&#xD;
Motor function was recorded separately for each leg resulting in total points of 0 to 14. Improvement of motor function was defined as an increase by at least 2 points compared to baseline.</description>
        <time_frame>at 1 month following radiotherapy</time_frame>
        <group_list>
          <group group_id="O1">
            <title>5 x 4 Gy in 1 Week</title>
            <description>radiotherapy with 5 x 4 Gy in 1 week (5 x 4 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
          </group>
          <group group_id="O2">
            <title>10 x 3 Gy in 2 Weeks</title>
            <description>radiotherapy with 10 x 3 Gy in 2 weeks (5 x 3 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Showing Improvement of Motor Deficits at 1 Month Following Radiotherapy</title>
          <description>Motor function was graded with the following 8-point scale: 0, complete paraplegia; 1, palpable or visible muscle contractions; 2, active movement of the leg without gravity; 3, active movement against gravity; 4, active movement against mild resistance; 5, active movement against intermediate resistance; 6, active movement against strong resistance; and 7, normal strength.&#xD;
Motor function was recorded separately for each leg resulting in total points of 0 to 14. Improvement of motor function was defined as an increase by at least 2 points compared to baseline.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="78"/>
                <count group_id="O2" value="77"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                    <measurement group_id="O2" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Experiencing at Least One Grade &gt;=2 Radiotherapy-related Toxicity</title>
        <description>Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) (version 4)</description>
        <time_frame>during radiotherapy and up to 6 months following radiotherapy</time_frame>
        <group_list>
          <group group_id="O1">
            <title>5 x 4 Gy in 1 Week</title>
            <description>radiotherapy with 5 x 4 Gy in 1 week (5 x 4 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
          </group>
          <group group_id="O2">
            <title>10 x 3 Gy in 2 Weeks</title>
            <description>radiotherapy with 10 x 3 Gy in 2 weeks (5 x 3 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Experiencing at Least One Grade &gt;=2 Radiotherapy-related Toxicity</title>
          <description>Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) (version 4)</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
                <count group_id="O2" value="102"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>at least 1 grade &gt;=2 radiotherapy-related toxicity</title>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>no grade &gt;=2 radiotherapy-related toxicity</title>
                  <measurement_list>
                    <measurement group_id="O1" value="90"/>
                    <measurement group_id="O2" value="87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>5 x 4 Gy in 1 Week</title>
          <description>radiotherapy with 5 x 4 Gy in 1 week (5 x 4 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
        </group>
        <group group_id="E2">
          <title>10 x 3 Gy in 2 Weeks</title>
          <description>radiotherapy with 10 x 3 Gy in 2 weeks (5 x 3 Gy per week)&#xD;
radiotherapy: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="58" subjects_at_risk="101"/>
                <counts group_id="E2" subjects_affected="62" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="101"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombopenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="101"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>reflux esophagitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="101"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>gastric ulcer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="101"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>hypotonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="101"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>sepsis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="101"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="101"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>subdural bleeding</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="101"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>desorientation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="101"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>acute renal failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="101"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>pneumonia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="101"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>pulmonary embolism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="101"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="101"/>
                <counts group_id="E2" subjects_affected="26" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>nausea/vomiting</sub_title>
                <counts group_id="E1" events="21" subjects_affected="16" subjects_at_risk="101"/>
                <counts group_id="E2" events="21" subjects_affected="20" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>diarrhea</sub_title>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="101"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>dysphagia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="101"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="101"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>gastritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="101"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>increased levels of transaminases</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="101"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>fatigue</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="101"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>cachexia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="101"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>pneumonia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="101"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="102"/>
              </event>
              <event>
                <sub_title>cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="101"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>radiation dermatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="101"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="102"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Prof. Dr. Dirk Rades</name_or_title>
      <organization>Department of Radiation Oncology, University of Lübeck, Germany</organization>
      <phone>0049 451 500 ext 45401</phone>
      <email>dirk.rades@uksh.de</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02189473
org study id: ARO 200901
nct id: NCT02189473
lead sponsor: 
has dmc: Yes
The primary aim of this randomized multi-center trial is to investigate the efficacy of the
      radiotherapy regimens 5 x 4 Gy and 10 x 3 Gy with respect to the effect on motor function in
      patients with metastatic epidural spinal cord compression.
The primary aim of this randomized multi-center trial is to investigate the efficacy of the
      radiotherapy regimens 5 x 4 Gy and 10 x 3 Gy with respect to the effect on motor function in
      patients with metastatic epidural spinal cord compression. The response rate (improvement in
      motor function or prevention of progression) will be assessed at one month following
      radiotherapy.

      In addition, the following endpoints will be evaluated:

        1. Motor function; additional assessments directly and at 3 and at 6 months after
           radiotherapy

        2. Ability to walk; assessment directly and at 1, 3 and 6 months after radiotherapy

        3. Sensory function; assessment directly and at 1, 3 and 6 months after radiotherapy

        4. Quality of life; evaluation directly and at 1, 3 and 6 months after radiotherapy

        5. Pain assessment directly and at 1, 3 and 6 months after radiotherapy

        6. Overall survival up to 6 months following radiotherapy

        7. Local Progression-free survival up to 6 months following radiotherapy
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants Showing Improvement or no Further Progression of Motor Deficits at 1 Month Following Radiotherapy
time frame: at 1 month following radiotherapy
description: Overall response was defined as improvement or no further progression of motor deficits following radiotherapy.
Motor function was graded with the following 8-point scale: 0, complete paraplegia; 1, palpable or visible muscle contractions; 2, active movement of the leg without gravity; 3, active movement against gravity; 4, active movement against mild resistance; 5, active movement against intermediate resistance; 6, active movement against strong resistance; and 7, normal strength.
Motor function was recorded separately for each leg resulting in total points of 0 to 14. Improvement of motor function was defined as an increase by at least 2 points compared to baseline. No further progression was defined as +/-1 point (i.e. +1 point, +/- 0 points or -1 point).
measure: Number of Participants Who Were Able to Walk at 1 Month Following Radiotherapy
time frame: at 1 month following radiotherapy
description: Ambulatory status was assessed using the following scoring system:
0 = Normal strength
= Ambulatory without aid
= Ambulatory with aid
= Not ambulatory
A patient with a score equal to or less than 2 is considered "able to walk". Both participants that could and could not walk prior to radiotherapy have been included in this assessment..
measure: Number of Participants Who Were Alive at 6 Months Following Radiotherapy Without Deterioration of Motor Function During (or Directly Following) Radiotherapy and Freedom From In-field Recurrence of Metastatic Spinal Cord Compression Following Radiotherapy
time frame: 6 months following radiotherapy
description: Local Progression Free Survival (LPFS) was defined as freedom from progression of motor deficits during or one month following radiotherapy and freedom from in-field recurrence of metastatic spinal cord compression (MSCC) following radiotherapy.
An in-field recurrence was defined as a recurrence of MSCC associated with motor deficits in the region of the spinal cord that had been previously irradiated for MSCC.
In case of clinical suspicion of sich a recurrence, a spinal MRI was performed to confirm the diagnosis. Time to in-field recurrence was calculated from the last day of radiotherapy, and the patients were followed for a maximum of 6 months after the end of radiotherapy. The values of 6-month LPFS were estimated using the Kaplan-Meier method.
measure: Number of Participants Who Experienced Relief of Distress at 1 Month Following Radiotherapy Compared to Baseline
time frame: at 1 month following radiotherapy
description: Distress (as an indicator of impairment of quality of life) was measured with the distress-thermometer. the patients rated their level of distress on a scale ranging from 0 (no distress) to 10 (extreme distress). Patients rated the distress they experienced during the last week and stated the reasons for distress from a list of items.
An improvement (lower score) by 2 points was considered a clinically relevant relief of distress. Patients with baseline-scores of 0-1 points were not included, since improvement by 2 points was not possible.
measure: Number of Participants Who Experienced Relief of Pain at 1 Month Following Radiotherapy Compared to Baseline
time frame: at 1 month following radiotherapy
description: Pain was measured with a numeric self-rating scale ranging from 0 (no pain) to 10 (worst pain).
Relief of pain was defined as improvement (=decrease of pain) by at least 2 points without increase of analgesics. Patients with baseline-scores of 0-1 points were not included, since improvement by 2 points was not possible.
measure: Number of Participants Who Were Alive at 6 Months Following Radiotherapy
time frame: 6 months following radiotherapy
description: Overall Survival (OS) was defined as freedom from death of any cause.
Time to death was calculated from the last day of radiotherapy, and the patients were followed for a maximum of 6 months after the end of radiotherapy. The values of 6-month OS were estimated using the Kaplan-Meier method.
measure: Number of Participants Showing Improvement of Motor Deficits at 1 Month Following Radiotherapy
time frame: at 1 month following radiotherapy
description: Motor function was graded with the following 8-point scale: 0, complete paraplegia; 1, palpable or visible muscle contractions; 2, active movement of the leg without gravity; 3, active movement against gravity; 4, active movement against mild resistance; 5, active movement against intermediate resistance; 6, active movement against strong resistance; and 7, normal strength.
Motor function was recorded separately for each leg resulting in total points of 0 to 14. Improvement of motor function was defined as an increase by at least 2 points compared to baseline.
measure: Number of Participants Experiencing at Least One Grade >=2 Radiotherapy-related Toxicity
time frame: during radiotherapy and up to 6 months following radiotherapy
description: Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) (version 4)
arm group label: 5 x 4 Gy in 1 week
arm group type: Experimental
description: radiotherapy with 5 x 4 Gy in 1 week (5 x 4 Gy per week)
arm group label: 10 x 3 Gy in 2 weeks
arm group type: Active Comparator
description: radiotherapy with 10 x 3 Gy in 2 weeks (5 x 3 Gy per week)
intervention type: Radiation
intervention name: radiotherapy
description: external beam radiotherapy (5 x 4 Gy versus 10 x 3 Gy)
arm group label: 10 x 3 Gy in 2 weeks
arm group label: 5 x 4 Gy in 1 week
criteria: 
gender: All
minimum age: 18 Years
maximum age: 89 Years
healthy volunteers: No
last name: Dirk Rades, MD
role: Study Chair
affiliation: Department of Radiation Oncology, University of Lübeck, Germany
facility: 
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country: Germany
country: Lithuania
country: Saudi Arabia
country: Slovenia
country: Spain
country: United States
citation: Maranzano E, Latini P. Effectiveness of radiation therapy without surgery in metastatic spinal cord compression: final results from a prospective trial. Int J Radiat Oncol Biol Phys. 1995 Jul 15;32(4):959-67. doi: 10.1016/0360-3016(95)00572-g.
PMID: 7607970
citation: Sorensen S, Borgesen SE, Rohde K, Rasmusson B, Bach F, Boge-Rasmussen T, Stjernholm P, Larsen BH, Agerlin N, Gjerris F, et al. Metastatic epidural spinal cord compression. Results of treatment and survival. Cancer. 1990 Apr 1;65(7):1502-8. doi: 10.1002/1097-0142(19900401)65:73.0.co;2-d.
PMID: 2311062
citation: Helweg-Larsen S, Sorensen PS, Kreiner S. Prognostic factors in metastatic spinal cord compression: a prospective study using multivariate analysis of variables influencing survival and gait function in 153 patients. Int J Radiat Oncol Biol Phys. 2000 Mar 15;46(5):1163-9. doi: 10.1016/s0360-3016(99)00333-8.
PMID: 10725627
citation: Leviov M, Dale J, Stein M, Ben-Shahar M, Ben-Arush M, Milstein D, Goldsher D, Kuten A. The management of metastatic spinal cord compression: a radiotherapeutic success ceiling. Int J Radiat Oncol Biol Phys. 1993 Sep 30;27(2):231-4. doi: 10.1016/0360-3016(93)90232-k.
PMID: 8407396
citation: Rades D, Blach M, Bremer M, Wildfang I, Karstens JH, Heidenreich F. Prognostic significance of the time of developing motor deficits before radiation therapy in metastatic spinal cord compression: one-year results of a prospective trial. Int J Radiat Oncol Biol Phys. 2000 Dec 1;48(5):1403-8. doi: 10.1016/s0360-3016(00)01408-5.
PMID: 11121640
citation: Rades D, Heidenreich F, Bremer M, Karstens JH. Time of developing motor deficits before radiotherapy as a new and relevant prognostic factor in metastatic spinal cord compression: final results of a retrospective analysis. Eur Neurol. 2001;45(4):266-9. doi: 10.1159/000052141.
PMID: 11385267
citation: Rades D, Heidenreich F, Karstens JH. Final results of a prospective study of the prognostic value of the time to develop motor deficits before irradiation in metastatic spinal cord compression. Int J Radiat Oncol Biol Phys. 2002 Jul 15;53(4):975-9. doi: 10.1016/s0360-3016(02)02819-5.
PMID: 12095565
citation: Arcangeli G, Giovinazzo G, Saracino B, D'Angelo L, Giannarelli D, Arcangeli G, Micheli A. Radiation therapy in the management of symptomatic bone metastases: the effect of total dose and histology on pain relief and response duration. Int J Radiat Oncol Biol Phys. 1998 Dec 1;42(5):1119-26. doi: 10.1016/s0360-3016(98)00264-8.
PMID: 9869238
citation: Niewald M, Tkocz HJ, Abel U, Scheib T, Walter K, Nieder C, Schnabel K, Berberich W, Kubale R, Fuchs M. Rapid course radiation therapy vs. more standard treatment: a randomized trial for bone metastases. Int J Radiat Oncol Biol Phys. 1996 Dec 1;36(5):1085-9. doi: 10.1016/s0360-3016(96)00388-4.
PMID: 8985030
citation: 8 Gy single fraction radiotherapy for the treatment of metastatic skeletal pain: randomised comparison with a multifraction schedule over 12 months of patient follow-up. Bone Pain Trial Working Party. Radiother Oncol. 1999 Aug;52(2):111-21.
PMID: 10577696
citation: Steenland E, Leer JW, van Houwelingen H, Post WJ, van den Hout WB, Kievit J, de Haes H, Martijn H, Oei B, Vonk E, van der Steen-Banasik E, Wiggenraad RG, Hoogenhout J, Warlam-Rodenhuis C, van Tienhoven G, Wanders R, Pomp J, van Reijn M, van Mierlo I, Rutten E. The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study. Radiother Oncol. 1999 Aug;52(2):101-9. doi: 10.1016/s0167-8140(99)00110-3. Erratum In: Radiother Oncol 1999 Nov;53(2):167. Leer, J [corrected to Leer, JW]; van Mierlo ,T [corrected to van Mierlo, I].
PMID: 10577695
citation: Rades D, Stalpers LJ, Veninga T, Schulte R, Hoskin PJ, Obralic N, Bajrovic A, Rudat V, Schwarz R, Hulshof MC, Poortmans P, Schild SE. Evaluation of five radiation schedules and prognostic factors for metastatic spinal cord compression. J Clin Oncol. 2005 May 20;23(15):3366-75. doi: 10.1200/JCO.2005.04.754.
PMID: 15908648
citation: Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, Shank B, Solin LJ, Wesson M. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991 May 15;21(1):109-22. doi: 10.1016/0360-3016(91)90171-y.
PMID: 2032882
citation: Barendsen GW. Dose fractionation, dose rate and iso-effect relationships for normal tissue responses. Int J Radiat Oncol Biol Phys. 1982 Nov;8(11):1981-97. doi: 10.1016/0360-3016(82)90459-x. No abstract available.
PMID: 6759484
citation: Koswig S, Budach V. [Remineralization and pain relief in bone metastases after after different radiotherapy fractions (10 times 3 Gy vs. 1 time 8 Gy). A prospective study]. Strahlenther Onkol. 1999 Oct;175(10):500-8. doi: 10.1007/s000660050061. German.
PMID: 10554645
citation: Rades D, Dunst J, Schild SE. The first score predicting overall survival in patients with metastatic spinal cord compression. Cancer. 2008 Jan 1;112(1):157-61. doi: 10.1002/cncr.23150.
PMID: 17948910
citation: Tomita T, Galicich JH, Sundaresan N. Radiation therapy for spinal epidural metastases with complete block. Acta Radiol Oncol. 1983;22(2):135-43. doi: 10.3109/02841868309134353.
PMID: 6310968
citation: Maranzano E, Bellavita R, Rossi R, De Angelis V, Frattegiani A, Bagnoli R, Mignogna M, Beneventi S, Lupattelli M, Ponticelli P, Biti GP, Latini P. Short-course versus split-course radiotherapy in metastatic spinal cord compression: results of a phase III, randomized, multicenter trial. J Clin Oncol. 2005 May 20;23(15):3358-65. doi: 10.1200/JCO.2005.08.193. Epub 2005 Feb 28.
PMID: 15738534
responsible party type: Sponsor-Investigator
investigator affiliation: University Hospital Schleswig-Holstein
investigator full name: Prof. Dirk Rades, MD
investigator title: Prof. Dr. Dirk Rades. MD
mesh term: Spinal Cord Compression
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 