<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/NCT01716949</url>
  </required_header>
  <id_info>
    <org_study_id>ESHO201107/001</org_study_id>
    <nct_id>NCT01716949</nct_id>
  </id_info>
  <brief_title>Neoadjuvant Chemoradiation With 5-FU(or Capecitabine) and Oxaliplatin Combined With Hyperthermia in Rectal Cancer</brief_title>
  <acronym>HyRec</acronym>
  <official_title>Multi-institutional Phase I/II Study: Neoadjuvant Chemoradiation With 5-FU (or Capecitabine) and Oxaliplatin Combined With Deep Regional Hyperthermia in Locally Advanced or Recurrent Rectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Erlangen-Nürnberg Medical School</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Erlangen-Nürnberg Medical School</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This trial examines the feasibility, effectiveness and safety of a combination of&#xD;
      radiotherapy (over a period of five weeks) and chemotherapy (with 5-FU or Capecitabine and&#xD;
      Oxaliplatin) and 10 fractions of deep regional hyperthermia in patients with primary locally&#xD;
      advanced or locally recurrent rectal cancer. Previous pelvic irradiation in case of a local&#xD;
      recurrence is not excluded from the trial. The treatment protocol aims on a preoperatively&#xD;
      improved tumor regression allowing less aggressive surgery in primary locally advanced rectal&#xD;
      cancer and a higher rate of curative resections in heavily pretreated locally recurrent&#xD;
      rectal cancers.&#xD;
&#xD;
      Primary endpoint of the trial is the feasibility rate of a multimodal regimen consisting of&#xD;
      radiochemotherapy and hyperthermia. Secondary endpoints are local control, survival rates,&#xD;
      and toxicity. It is planned to include a total number of 59 patients over a period of 2.5&#xD;
      years.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2012</start_date>
  <completion_date type="Anticipated">June 2023</completion_date>
  <primary_completion_date type="Anticipated">June 2022</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Feasibility rate (i.e. rate of patients not experiencing dose-limiting toxicity [DLT])</measure>
    <time_frame>Participants will be followed for the duration of therapy and for 6 weeks after the last study treatment dose (approximately 11 to 12 weeks)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of hyperthermia applications by patient</measure>
    <time_frame>Duration of therapy (approximately 5 to 6 weeks)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Local progression-free survival</measure>
    <time_frame>Participants will be followed for up to 5 years after the end of therapy (Follow up period)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Distant metastasis-free survival</measure>
    <time_frame>Participants will be followed for up to 5 years after the end of therapy (Follow up period)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Participants will be followed for up to 5 years after the end of therapy (Follow up period)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rate</measure>
    <time_frame>Participants will be followed for up to 5 years after the end of therapy (Follow up period)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of R0-resections</measure>
    <time_frame>Only of participants who are considered as resectable receive surgery in curative intention 4-6 weeks after completion of chemoradiation (results app. after 10 to 12 weeks after start of therapy)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of acute and late toxicity</measure>
    <time_frame>Participants will be followed for up to 5 years after the end of therapy (Follow up period)</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">59</enrollment>
  <condition>Rectal Cancer</condition>
  <arm_group>
    <arm_group_label>HyRec</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Radiotherapy, Hyperthermia, 5-Fluorouracil (may be replaced by Capecitabine), Capecitabine (may be replaced by 5-Fluorouracil), Oxaliplatin</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiotherapy</intervention_name>
    <description>45 up to 50.4 Gy; daily dose 1,8 Gy, 5 days per weeks</description>
    <arm_group_label>HyRec</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Hyperthermia</intervention_name>
    <description>10 sessions, therapeutic time 60 min</description>
    <arm_group_label>HyRec</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5-Fluorouracil</intervention_name>
    <description>250 mg/m^2/d as continuous i.v. infusion on d1-14, 22-35 (may be preplaced by Capecitabine)</description>
    <arm_group_label>HyRec</arm_group_label>
    <other_name>all brands of 5-Fluorouracil are allowed</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>1650 mg/m^2/d oral intake d1-14, 22-35 (may be replaced by 5-Fluorouracil)</description>
    <arm_group_label>HyRec</arm_group_label>
    <other_name>all brands of Capecitabine are allowed</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>50 mg/m^2/d as 2-hour bolus infusion on d2, 9, 23, 30</description>
    <arm_group_label>HyRec</arm_group_label>
    <other_name>all brands of oxaliplatin are allowed</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Histologically confirmed, locally advanced or recurrent (any recurrence of tumor&#xD;
             within the lesser pelvis; resectable or non-resectable) adenocarcinoma of the rectum&#xD;
             (UICC stage IIB-IV); distant oligo-metastases may be present.&#xD;
&#xD;
          -  ECOG-performance status &lt; 2&#xD;
&#xD;
          -  Sufficient bone marrow function:&#xD;
&#xD;
          -  WBC &gt; 3,5 x 10^9/l&#xD;
&#xD;
          -  Neutrophil granulocytes &gt; 1,5 x 10^9/l&#xD;
&#xD;
          -  Platelets &gt; 100 x 10^9/l&#xD;
&#xD;
          -  Hemoglobin &gt; 10 g/dl&#xD;
&#xD;
          -  Sufficient liver function: Bilirubin &lt; 2,0 mg%, SGOT, SGPT, alkaline phosphatase, gGT&#xD;
             less than 3 times upper limit of normal&#xD;
&#xD;
          -  Serum creatinine &lt; 1,5 mg%, glomerular filtration rate (or comparable test) &gt; 50&#xD;
             ml/min&#xD;
&#xD;
          -  Signed study-specific consent form prior to therapy&#xD;
&#xD;
          -  Fertile patients must use effective contraception during and for 6 months after study&#xD;
             treatment&#xD;
&#xD;
          -  Considered fit for oxaliplatin and 5-FU-containing combination chemotherapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pelvic radiotherapy during the last 12 months&#xD;
&#xD;
          -  Pregnant or lactating/nursing women&#xD;
&#xD;
          -  Drug addiction&#xD;
&#xD;
          -  On-treatment participation on other trials&#xD;
&#xD;
          -  Active intractable or uncontrollable infection&#xD;
&#xD;
          -  Prior or concurrent malignancy (≤ 5 years prior to enrolment in study) except rectal&#xD;
             cancer or non-melanoma skin cancer or cervical carcinoma FIGO stage 0-1 if the patient&#xD;
             is continuously disease-free&#xD;
&#xD;
          -  Chronic diarrhea (&gt; NCI CTC-Grad 1)&#xD;
&#xD;
          -  Chronic inflammatory disease of the intestine&#xD;
&#xD;
          -  Collagen vascular disease&#xD;
&#xD;
          -  The presence of congenital diseases with increased radiation sensitivity, for example&#xD;
             teleangiectatic ataxia, or similar&#xD;
&#xD;
          -  Pre-existing uncontrolled cardiac disease, signs of cardiac failure, or rhythm&#xD;
             disturbances requiring therapy&#xD;
&#xD;
          -  Myocardial infarction within the past 12 months&#xD;
&#xD;
          -  Congestive heart failure&#xD;
&#xD;
          -  Complete bundle branch block&#xD;
&#xD;
          -  New York Heart Association (NYHA) class III or IV heart disease&#xD;
&#xD;
          -  Known allergic reactions on study medication&#xD;
&#xD;
          -  Cardiac pacemaker&#xD;
&#xD;
          -  Disease that would preclude chemoradiation or deep regional hyperthermia&#xD;
&#xD;
          -  Any metal implants (with exception of non-clustered marker clips)&#xD;
&#xD;
          -  Psychological, familial, sociological, or geographical condition that would preclude&#xD;
             study compliance&#xD;
&#xD;
          -  Patients deemed technically unsatisfactory for deep regional hyperthermia&#xD;
&#xD;
          -  Cardiac symptoms (&gt; NCI CTCAE Grade 1) due to pretreatment with fluoropyrimidines&#xD;
&#xD;
          -  Neurological symptoms (&gt; NCI CTCAE Grade 1) due to pretreatment with oxaliplatin&#xD;
&#xD;
          -  Rare hereditary problems of galactose intolerance, Lapp lactase deficiency or&#xD;
             glucose-galactose malabsorption&#xD;
&#xD;
          -  Oral anticoagulation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Oliver Ott, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Strahlenklinik, Universitätsklinikum Erlangen</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Oliver Ott, MD</last_name>
    <phone>++49(0)9131-85</phone>
    <phone_ext>33968</phone_ext>
    <email>st-studiensekretatiat@uk-erlangen.de</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sebastian Lettmaier, MD</last_name>
    <phone>++49(0)9131-85</phone>
    <phone_ext>33968</phone_ext>
    <email>st-studiensekretariat@uk-erlangen.de</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Klinik Bad Trissl, Innere Medizin</name>
      <address>
        <city>Bad Trissl</city>
        <zip>83080</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Bernhard Weber, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Friedemann Peschke, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Hospital</name>
      <address>
        <city>Duesseldorf</city>
        <zip>40225</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Christiane Matuschek, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Erlangen, Strahlenklinik</name>
      <address>
        <city>Erlangen</city>
        <zip>91054</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Oliver Ott, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Rainer Fietkau, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>LMU München, Campus Großhadern, Medizinische Klinik III, Hyperthermie</name>
      <address>
        <city>München</city>
        <zip>81377</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Rolf Issels, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Katharina Lechner, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Schlossbergklinik</name>
      <address>
        <city>Oberstaufen</city>
        <zip>87534</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Thomas Licht, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Blair Wolfgang, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Tübingen, Radioonkologie</name>
      <address>
        <city>Tübingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Daniel Zips, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Johanna Gellermann, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>October 5, 2012</study_first_submitted>
  <study_first_submitted_qc>October 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 30, 2012</study_first_posted>
  <last_update_submitted>August 9, 2017</last_update_submitted>
  <last_update_submitted_qc>August 9, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 11, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>rectal cancer</keyword>
  <keyword>recurrent rectal cancer</keyword>
  <keyword>hyperthermia</keyword>
  <keyword>radiation</keyword>
  <keyword>chemoradiation</keyword>
  <keyword>5-FU</keyword>
  <keyword>capecitabine</keyword>
  <keyword>oxaliplatin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rectal Neoplasms</mesh_term>
    <mesh_term>Hyperthermia</mesh_term>
    <mesh_term>Fever</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Capecitabine</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01716949
org study id: ESHO201107/001
nct id: NCT01716949
lead sponsor: 
has dmc: No
This trial examines the feasibility, effectiveness and safety of a combination of
      radiotherapy (over a period of five weeks) and chemotherapy (with 5-FU or Capecitabine and
      Oxaliplatin) and 10 fractions of deep regional hyperthermia in patients with primary locally
      advanced or locally recurrent rectal cancer. Previous pelvic irradiation in case of a local
      recurrence is not excluded from the trial. The treatment protocol aims on a preoperatively
      improved tumor regression allowing less aggressive surgery in primary locally advanced rectal
      cancer and a higher rate of curative resections in heavily pretreated locally recurrent
      rectal cancers.

      Primary endpoint of the trial is the feasibility rate of a multimodal regimen consisting of
      radiochemotherapy and hyperthermia. Secondary endpoints are local control, survival rates,
      and toxicity. It is planned to include a total number of 59 patients over a period of 2.5
      years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Feasibility rate (i.e. rate of patients not experiencing dose-limiting toxicity [DLT])
time frame: Participants will be followed for the duration of therapy and for 6 weeks after the last study treatment dose (approximately 11 to 12 weeks)
measure: Number of hyperthermia applications by patient
time frame: Duration of therapy (approximately 5 to 6 weeks)
measure: Local progression-free survival
time frame: Participants will be followed for up to 5 years after the end of therapy (Follow up period)
measure: Distant metastasis-free survival
time frame: Participants will be followed for up to 5 years after the end of therapy (Follow up period)
measure: Overall survival
time frame: Participants will be followed for up to 5 years after the end of therapy (Follow up period)
measure: Response rate
time frame: Participants will be followed for up to 5 years after the end of therapy (Follow up period)
measure: Rate of R0-resections
time frame: Only of participants who are considered as resectable receive surgery in curative intention 4-6 weeks after completion of chemoradiation (results app. after 10 to 12 weeks after start of therapy)
measure: Rate of acute and late toxicity
time frame: Participants will be followed for up to 5 years after the end of therapy (Follow up period)
arm group label: HyRec
arm group type: Experimental
description: Radiotherapy, Hyperthermia, 5-Fluorouracil (may be replaced by Capecitabine), Capecitabine (may be replaced by 5-Fluorouracil), Oxaliplatin
intervention type: Radiation
intervention name: Radiotherapy
description: 45 up to 50.4 Gy; daily dose 1,8 Gy, 5 days per weeks
arm group label: HyRec
intervention type: Procedure
intervention name: Hyperthermia
description: 10 sessions, therapeutic time 60 min
arm group label: HyRec
intervention type: Drug
intervention name: 5-Fluorouracil
description: 250 mg/m^2/d as continuous i.v. infusion on d1-14, 22-35 (may be preplaced by Capecitabine)
arm group label: HyRec
other name: all brands of 5-Fluorouracil are allowed
intervention type: Drug
intervention name: Capecitabine
description: 1650 mg/m^2/d oral intake d1-14, 22-35 (may be replaced by 5-Fluorouracil)
arm group label: HyRec
other name: all brands of Capecitabine are allowed
intervention type: Drug
intervention name: Oxaliplatin
description: 50 mg/m^2/d as 2-hour bolus infusion on d2, 9, 23, 30
arm group label: HyRec
other name: all brands of oxaliplatin are allowed
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Oliver Ott, MD
role: Principal Investigator
affiliation: Strahlenklinik, Universitätsklinikum Erlangen
last name: Oliver Ott, MD
phone: ++49(0)9131-85
phone ext: 33968
email: st-studiensekretatiat@uk-erlangen.de
last name: Sebastian Lettmaier, MD
phone: ++49(0)9131-85
phone ext: 33968
email: st-studiensekretariat@uk-erlangen.de
facility: 
status: Recruiting
investigator: 
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
investigator: 
facility: 
status: Recruiting
investigator: 
investigator: 
facility: 
status: Recruiting
investigator: 
investigator: 
facility: 
status: Recruiting
investigator: 
investigator: 
country: Germany
responsible party type: Sponsor
mesh term: Rectal Neoplasms
mesh term: Hyperthermia
mesh term: Fever
mesh term: Fluorouracil
mesh term: Capecitabine
mesh term: Oxaliplatin