<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/NCT02208128</url>
  </required_header>
  <id_info>
    <org_study_id>S-539/2013</org_study_id>
    <secondary_id>DRKS00006193</secondary_id>
    <nct_id>NCT02208128</nct_id>
  </id_info>
  <brief_title>Molecular Determinants for Therapy Response on Renal Cell Carcinoma</brief_title>
  <acronym>MORE</acronym>
  <official_title>Molecular Determinants for Therapy Response on Renal Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Heidelberg University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Heidelberg University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Aim of the scientific analysis is to find biological factors (biomarkers) allowing a&#xD;
      prediction of disease progression and a better choice of therapy. After diagnosis the kidney&#xD;
      and the tumor will be removed by standard surgery followed by drug therapy. Within surgery&#xD;
      remaining tumor tissue will be used for the scientific analysis. In case of disease&#xD;
      progression during the drug treatment the drug therapy will be changed. Before therapy change&#xD;
      a small tissue sample will be collected for molecular diagnostics. This will be done by&#xD;
      puncture through the skin under local anesthesia. Blood samples taken before surgery and at&#xD;
      the time of first and second disease progression will also be used for molecular-biological&#xD;
      analysis. As there is no clear recommendation for drug therapy after disease progression this&#xD;
      study should serve to determine an individual therapy on the basis of the molecular profile&#xD;
      and the molecular changes. As the tumor disease changes and developes resistance to drugs,&#xD;
      analysis at the time of disease progression shall identify biological factors which will&#xD;
      predict a likelihood response to a specific drugs.&#xD;
&#xD;
      This shall allow to give the patient an individual therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Aim of this study is to perform a profound molecular analysis of the tumor before beginning&#xD;
      therapy and after failure of the approved targeted first-and second line therapy (standard&#xD;
      therapy). The tumor sample will be analyzed by using profound molecular analysis to identify&#xD;
      target structures which will predict the efficacy of a specific therapy (substance group)and&#xD;
      therefore have a predictive value. The analysis of molecular biomarkers include the genomic&#xD;
      sequencing of targeted areas or of the entire DNA of the tumor tissue comparative to the DNA&#xD;
      of healthy cells, the measurement of DNA-regulatory elements (methylation, mi-RNA expression,&#xD;
      protein expression analytics, functional tumorcell analysis in-vitro, efficacy analysis in&#xD;
      cell culture or in animal model) who are supposed to inspect the biological influence of the&#xD;
      molecular biomarkers and measurements of free tumor DNA out of the blood.&#xD;
&#xD;
      The response to the established standard therapy in the first and second line will be&#xD;
      acquired due to all clinical and radiological established standard parameters. The&#xD;
      clinical-radiological response will be correlated with the molecular changes and their&#xD;
      changes in therapy process to allow predictive prognosis for a further therapy.&#xD;
&#xD;
      There is no approved clinical standard for third line therapy. However there are further&#xD;
      medications approved without any scientific evidence of their efficacy in this therapy&#xD;
      situation (third line treatment after failure of first and second line treatment) and for&#xD;
      which a response of under 6 weeks is expected.&#xD;
&#xD;
      For these patients the third line therapy will be adjusted to the molecular profiles of the&#xD;
      previous therapies. Therefore the oncological history of the noticed marker profiles and the&#xD;
      presence of target structures (from whom it is known that they are influenced by certain&#xD;
      substances) will be considered.&#xD;
&#xD;
      The therapy will use substances which are approved in general for the treatment of metastatic&#xD;
      renal cell cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>May 2014</start_date>
  <completion_date type="Anticipated">February 2018</completion_date>
  <primary_completion_date type="Anticipated">February 2018</primary_completion_date>
  <phase>N/A</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>Time to disease progression in third line therapy</measure>
    <time_frame>Approximately 2 years depending on when the failure in third line therapy happens</time_frame>
    <description>Progression free survival in third-line therapy ( defined as the time from beginning of the third-line therapy to the date of the first documented progression as determined by the investigator using Response Evaluation Criteria in Solid Tumors criteria assessed by CT/MRI every 12 weeks).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Identification of preventive biomarkers.</measure>
    <time_frame>2weeks in average before surgery and 4 weeks in average after surgery before starting first line treatment</time_frame>
    <description>Identification of preventive biomarkers.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Identification of preventive biomarkers</measure>
    <time_frame>2years</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">4</enrollment>
  <condition>Renal Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Receptor-Tyrosinkinase-Inhibitor</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Guidelines-oriented therapy with approved systemic medications for renal cell carcinoma individually for each patient (Receptor-Tyrosinkinase-Inhibitor) (e.g.Sunitinib, Pazopanib, Bevacizumab, Everolimus, Axitinib, Temsirolimus). With 1.progression turning to second line treatment with one of the upper mentioned medications. Third line therapy due to the individual molecular modifications for each patient.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sunitinib, Pazopanib, Bevacizumab, Everolimus...</intervention_name>
    <description>Clinical standard</description>
    <arm_group_label>Receptor-Tyrosinkinase-Inhibitor</arm_group_label>
    <other_name>e.g.Sunitinib, Pazopanib, Bevacizumab, Everolimus...</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Minimum Age: 18 Years Maximum Age: no maximum age&#xD;
&#xD;
          -  metastatic lesions easy of access for puncture for specimen storage&#xD;
&#xD;
          -  histological subtype: clear-cell renal cancer&#xD;
&#xD;
          -  no contraindications against systemic therapy&#xD;
&#xD;
          -  indication for systemic therapy given&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  preexisting mental illness&#xD;
&#xD;
          -  further active malignancy&#xD;
&#xD;
          -  patients with increased risk of bleeding and/or wound healing disorder&#xD;
&#xD;
          -  patients who are not legally competent or unable to consent&#xD;
&#xD;
          -  contraindication for surgical intervention&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sascha Pahernil, PD Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Heidelberg, Urological Department</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sascha Pahernik, PD Dr.</last_name>
    <phone>+49 6221 5639689</phone>
    <email>sascha.pahernik@med.uni-heidelberg.de</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Carsten Grüllich, PD Dr.</last_name>
    <phone>+49 6221 5637125</phone>
    <email>carsten.gruellich@med.uni-heidelberg.de</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Urological Department of the University Hospital Heidelberg</name>
      <address>
        <city>Heidelberg</city>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sascha Pahernik, PD Dr.</last_name>
      <phone>+49 6221 56 39689</phone>
      <email>sascha.pahernik@med.uni-heidelberg.de</email>
    </contact>
    <investigator>
      <last_name>Sascha Pahernik, PD Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>June 2, 2014</study_first_submitted>
  <study_first_submitted_qc>July 31, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 4, 2014</study_first_posted>
  <last_update_submitted>July 31, 2014</last_update_submitted>
  <last_update_submitted_qc>July 31, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 4, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Renal cell carcinoma</keyword>
  <keyword>Biomarkers</keyword>
  <keyword>Molecular modifications</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Renal Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bevacizumab</mesh_term>
    <mesh_term>Sunitinib</mesh_term>
    <mesh_term>Everolimus</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/NCT02208128
org study id: S-539/2013
secondary id: DRKS00006193
nct id: NCT02208128
lead sponsor: 
has dmc: Yes
Aim of the scientific analysis is to find biological factors (biomarkers) allowing a
      prediction of disease progression and a better choice of therapy. After diagnosis the kidney
      and the tumor will be removed by standard surgery followed by drug therapy. Within surgery
      remaining tumor tissue will be used for the scientific analysis. In case of disease
      progression during the drug treatment the drug therapy will be changed. Before therapy change
      a small tissue sample will be collected for molecular diagnostics. This will be done by
      puncture through the skin under local anesthesia. Blood samples taken before surgery and at
      the time of first and second disease progression will also be used for molecular-biological
      analysis. As there is no clear recommendation for drug therapy after disease progression this
      study should serve to determine an individual therapy on the basis of the molecular profile
      and the molecular changes. As the tumor disease changes and developes resistance to drugs,
      analysis at the time of disease progression shall identify biological factors which will
      predict a likelihood response to a specific drugs.

      This shall allow to give the patient an individual therapy.
Aim of this study is to perform a profound molecular analysis of the tumor before beginning
      therapy and after failure of the approved targeted first-and second line therapy (standard
      therapy). The tumor sample will be analyzed by using profound molecular analysis to identify
      target structures which will predict the efficacy of a specific therapy (substance group)and
      therefore have a predictive value. The analysis of molecular biomarkers include the genomic
      sequencing of targeted areas or of the entire DNA of the tumor tissue comparative to the DNA
      of healthy cells, the measurement of DNA-regulatory elements (methylation, mi-RNA expression,
      protein expression analytics, functional tumorcell analysis in-vitro, efficacy analysis in
      cell culture or in animal model) who are supposed to inspect the biological influence of the
      molecular biomarkers and measurements of free tumor DNA out of the blood.

      The response to the established standard therapy in the first and second line will be
      acquired due to all clinical and radiological established standard parameters. The
      clinical-radiological response will be correlated with the molecular changes and their
      changes in therapy process to allow predictive prognosis for a further therapy.

      There is no approved clinical standard for third line therapy. However there are further
      medications approved without any scientific evidence of their efficacy in this therapy
      situation (third line treatment after failure of first and second line treatment) and for
      which a response of under 6 weeks is expected.

      For these patients the third line therapy will be adjusted to the molecular profiles of the
      previous therapies. Therefore the oncological history of the noticed marker profiles and the
      presence of target structures (from whom it is known that they are influenced by certain
      substances) will be considered.

      The therapy will use substances which are approved in general for the treatment of metastatic
      renal cell cancer.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Time to disease progression in third line therapy
time frame: Approximately 2 years depending on when the failure in third line therapy happens
description: Progression free survival in third-line therapy ( defined as the time from beginning of the third-line therapy to the date of the first documented progression as determined by the investigator using Response Evaluation Criteria in Solid Tumors criteria assessed by CT/MRI every 12 weeks).
measure: Identification of preventive biomarkers.
time frame: 2weeks in average before surgery and 4 weeks in average after surgery before starting first line treatment
description: Identification of preventive biomarkers.
measure: Identification of preventive biomarkers
time frame: 2years
arm group label: Receptor-Tyrosinkinase-Inhibitor
arm group type: No Intervention
description: Guidelines-oriented therapy with approved systemic medications for renal cell carcinoma individually for each patient (Receptor-Tyrosinkinase-Inhibitor) (e.g.Sunitinib, Pazopanib, Bevacizumab, Everolimus, Axitinib, Temsirolimus). With 1.progression turning to second line treatment with one of the upper mentioned medications. Third line therapy due to the individual molecular modifications for each patient.
intervention type: Drug
intervention name: Sunitinib, Pazopanib, Bevacizumab, Everolimus...
description: Clinical standard
arm group label: Receptor-Tyrosinkinase-Inhibitor
other name: e.g.Sunitinib, Pazopanib, Bevacizumab, Everolimus...
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Sascha Pahernil, PD Dr.
role: Principal Investigator
affiliation: University of Heidelberg, Urological Department
last name: Sascha Pahernik, PD Dr.
phone: +49 6221 5639689
email: sascha.pahernik@med.uni-heidelberg.de
last name: Carsten Grüllich, PD Dr.
phone: +49 6221 5637125
email: carsten.gruellich@med.uni-heidelberg.de
facility: 
status: Recruiting
contact: 
investigator: 
country: Germany
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Renal Cell
mesh term: Bevacizumab
mesh term: Sunitinib
mesh term: Everolimus