<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/NCT01715935</url>
  </required_header>
  <id_info>
    <org_study_id>2011-000882-11</org_study_id>
    <nct_id>NCT01715935</nct_id>
  </id_info>
  <brief_title>Biomarkers Before and After Nephrectomy of Locally Advanced or Metastatic Renal Cell Carcinoma Treated With Everolimus</brief_title>
  <acronym>NEORAD</acronym>
  <official_title>A Comparison of Blood and Tissue Biomarkers Before and After Nephrectomy in the First-line Setting With Everolimus in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Disease and Stage: Metastatic and locally advanced clear cell renal carcinoma&#xD;
&#xD;
      An open-label, exploratory, single-arm, multicenter trial.&#xD;
&#xD;
      Everolimus will be administered orally, once daily, for 6 weeks followed by a 1-week rest&#xD;
      period prior to nephrectomy.&#xD;
&#xD;
      Two to four weeks after surgery, everolimus will be reintroduced only for metastatic patients&#xD;
      until disease progression, unacceptable toxicity, withdrawal of patient consent, or other&#xD;
      stopping rules are met.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      An open-label, exploratory, single-arm, multicenter trial. Treatment with everolimus will be&#xD;
      initiated once patients have undergone baseline screening and provided their written informed&#xD;
      consent.&#xD;
&#xD;
      Everolimus will be administered orally, once daily, for 6 weeks followed by a 1-week rest&#xD;
      period prior to surgery. The starting dose will be 10 mg daily with provision for dose&#xD;
      reduction based on tolerability.&#xD;
&#xD;
      Radical nephrectomy will be performed at the end of week 7. For metastatic patients, two to&#xD;
      four weeks after surgery, everolimus will be reintroduced. Treatment will be continued until&#xD;
      disease progression, unacceptable toxicity, withdrawal of patient consent, or other stopping&#xD;
      rules are met.&#xD;
&#xD;
      Patients with locally advanced renal carcinoma will stop drug intake before nephrectomy.&#xD;
&#xD;
      Resumption of everolimus may be postponed in cases of a delay in wound healing or surgical&#xD;
      complications.&#xD;
&#xD;
      After treatment discontinuation and the last treatment visit (28-days after the last dose),&#xD;
      patients will be followed up in order to collect data on the onset of progression and&#xD;
      survival. In metastatic patients discontinuing treatment for reasons other than disease&#xD;
      progression, tumor assessment will continue every 3 months, until disease progression or&#xD;
      initiation of other anticancer therapy for up to one year of follow-up.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2012</start_date>
  <completion_date type="Actual">April 2016</completion_date>
  <primary_completion_date type="Actual">June 2015</primary_completion_date>
  <phase>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>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective clinical benefit</measure>
    <time_frame>After 6 weeks of treatment</time_frame>
    <description>Objective clinical benefit is defined as complete response, partial response or stable disease according to RECIST criteria version 1.1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>up to 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>up to 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability</measure>
    <time_frame>Participants will be followed all along the treatment period, an expected average of 15 months</time_frame>
    <description>Toxicity will be classify according to NCI-CTC criteria Version 4.0</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Clear-cell Renal Carcinoma</condition>
  <condition>Clear-cell Metastatic Renal Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>everolimus</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>everolimus, 10 mg PO daily. Before nephrectomy: 6 continuous weeks of treatment and one week of rest After nephrectomy: 4 weeks courses (for metastatic patients only)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Everolimus</intervention_name>
    <description>everolimus, 10 mg PO daily. Before nephrectomy: 6 continuous weeks of treatment and one week of rest After nephrectomy: 4 weeks courses (for metastatic patients only)</description>
    <arm_group_label>everolimus</arm_group_label>
    <other_name>AFINITOR</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Advanced RCC or a resectable renal tumor and at least one measurable inoperable&#xD;
             metastasis (at least 1 cm), in whom anti-angiogenic therapy is indicated&#xD;
&#xD;
          -  Patients without target lesions, with bone metastasis&#xD;
&#xD;
          -  Histologically confirmed clear cells RCC and possibility of adequate tumor sampling&#xD;
             prior to treatment&#xD;
&#xD;
          -  No prior systemic treatment for RCC&#xD;
&#xD;
          -  Male or female, at least 18 years&#xD;
&#xD;
          -  PS ECOG 0-1&#xD;
&#xD;
          -  Life expectancy at least 3 months&#xD;
&#xD;
          -  Adequate organ function with the following criteria:&#xD;
&#xD;
               -  Total serum bilirubin equal or less than 2 x ULN (Gilbert's disease exempted)&#xD;
&#xD;
               -  Serum transaminases and alkaline phosphatases equal or less than 2.5 x ULN, or in&#xD;
                  case of liver or bone metastasis equal or less than 5x ULN&#xD;
&#xD;
               -  Serum creatinine equal or less than 2 x ULN, creatinine clearance at least 50&#xD;
                  ml/min&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) at least 1500/mm3&#xD;
&#xD;
               -  Platelets at least 100,000/mm3&#xD;
&#xD;
               -  Hemoglobin at least 10.0 g/dL&#xD;
&#xD;
               -  INR equal or less than 1.7 or prothrombin time (PT) equal or less than 6 sec&#xD;
&#xD;
               -  Blood glucose less than 1.5x ULN&#xD;
&#xD;
               -  Fasting cholesterol equal or less than 5 mmol/L, triglycerides equal or less than&#xD;
                  200 mg/dl,&#xD;
&#xD;
          -  Negative pregnancy test within 7 days prior to enrollment&#xD;
&#xD;
          -  Signed and dated IRB/ICE-approved informed consent form&#xD;
&#xD;
          -  Willingness and ability to comply with scheduled visits, treatment plans, laboratory&#xD;
             tests and other study procedures.&#xD;
&#xD;
          -  Patient covered by the national health system&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous nephrectomy&#xD;
&#xD;
          -  Histology: any histologic type different than ccRCC&#xD;
&#xD;
          -  Treatment in a clinical trial in the last 30 days&#xD;
&#xD;
          -  Previous treatment with everolimus or other mTOR-inhibitors and anti-angiogenic drugs&#xD;
&#xD;
          -  Any of the following within 12 months prior to treatment initiation: severe/unstable&#xD;
             angina, myocardial infarction, coronary artery bypass graft, symptomatic congestive&#xD;
             heart failure, ischemic or hemorrhagic stroke including transient ischemic attack,&#xD;
             abnormal lung function.&#xD;
&#xD;
          -  Uncontrolled hypertension defined as systolic blood pressure &gt;150 mmHg or diastolic&#xD;
             pressure &gt;90 mmHg, despite optimal medical treatment&#xD;
&#xD;
          -  Abnormal ECG (Clinically significant)&#xD;
&#xD;
          -  Treatment with vitamin K antagonists. Ongoing treatment with therapeutic doses of&#xD;
             coumarin derivative anticoagulants (e.g. warfarin) or treatment within the 2 weeks&#xD;
             before the first day of everolimus administration. Prophylaxis with low dose warfarin&#xD;
             for deep vein thrombosis is permitted (up to 2 mg/day). Low molecular weight heparin&#xD;
             is allowed.&#xD;
&#xD;
          -  Brain metastasis. (Brain scan or MRI is mandatory). Note: Previous treated brain&#xD;
             metastasis (surgery ± radiotherapy, radiotherapy, radiosurgery or gammaknife) and&#xD;
             satisfying the following three criteria are allowed:&#xD;
&#xD;
               -  Asymptomatic;&#xD;
&#xD;
               -  No evidence of any active brain metastasis 3 months prior inclusion;&#xD;
&#xD;
               -  No necessity of corticoid or antiepileptic treatment.&#xD;
&#xD;
          -  Pregnancy or breastfeeding.&#xD;
&#xD;
          -  Any second malignancy within the last 3 years with the exception of basal cell&#xD;
             carcinoma, in situ cervical cancer and pT1/a bladder cancer with no evidence of&#xD;
             recurrent disease for 12 months.&#xD;
&#xD;
          -  Clinically significant gastrointestinal abnormalities including but not limited to:&#xD;
&#xD;
               -  Malabsorption syndrome&#xD;
&#xD;
               -  Major resection of the stomach or small bowel that could affect the absorption of&#xD;
                  the study drug&#xD;
&#xD;
               -  Active peptic ulcer disease&#xD;
&#xD;
               -  Inflammatory bowel disease&#xD;
&#xD;
               -  Ulcerative colitis or other gastrointestinal conditions with increased risk of&#xD;
                  perforation&#xD;
&#xD;
               -  History of abdominal fistula, gastrointestinal perforation, or intra abdominal&#xD;
                  abscess within 28 days prior to beginning study treatment&#xD;
&#xD;
               -  Hepatitis B/C&#xD;
&#xD;
          -  Hypersensitivity to everolimus or any excipient of everolimus.&#xD;
&#xD;
          -  Any active (acute or chronic) or uncontrolled infection/disorders that impair the&#xD;
             ability to evaluate the patient or for the patient to complete the study.&#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>Stéphane Oudard, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hôpital Européen Georges Pompidou, Paris (France)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHRU Besançon</name>
      <address>
        <city>Besançon</city>
        <zip>25000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Henri Mondor</name>
      <address>
        <city>Créteil</city>
        <zip>94000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Départemental Vendée</name>
      <address>
        <city>La Roche-sur-Yon</city>
        <zip>85925 cedex 9</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint Eloi - CHU Montpellier</name>
      <address>
        <city>Montpellier</city>
        <zip>34285 cedex 5</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fôpital d'Instruction des Amées du Val de Grâce</name>
      <address>
        <city>Paris</city>
        <zip>75005</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Cochin</name>
      <address>
        <city>Paris</city>
        <zip>75014</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Européen Georges Pompidou - Service d'oncologie médicale</name>
      <address>
        <city>Paris</city>
        <zip>7505</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut de Cancérologie Lucien Neuwirth</name>
      <address>
        <city>Saint Priest en Jarez</city>
        <zip>42270</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Alexis Vautrin</name>
      <address>
        <city>Vandoeuvre-lès-nancy</city>
        <zip>54511</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <zip>94805 cedex</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>February 2016</verification_date>
  <study_first_submitted>September 12, 2012</study_first_submitted>
  <study_first_submitted_qc>October 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 29, 2012</study_first_posted>
  <last_update_submitted>August 18, 2016</last_update_submitted>
  <last_update_submitted_qc>August 18, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 19, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Clear cells renal carcinoma</keyword>
  <keyword>everolimus</keyword>
  <keyword>neo-adjuvant treatment</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>
    <mesh_term>Kidney Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Everolimus</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01715935
org study id: 2011-000882-11
nct id: NCT01715935
lead sponsor: 
has dmc: No
Disease and Stage: Metastatic and locally advanced clear cell renal carcinoma

      An open-label, exploratory, single-arm, multicenter trial.

      Everolimus will be administered orally, once daily, for 6 weeks followed by a 1-week rest
      period prior to nephrectomy.

      Two to four weeks after surgery, everolimus will be reintroduced only for metastatic patients
      until disease progression, unacceptable toxicity, withdrawal of patient consent, or other
      stopping rules are met.
An open-label, exploratory, single-arm, multicenter trial. Treatment with everolimus will be
      initiated once patients have undergone baseline screening and provided their written informed
      consent.

      Everolimus will be administered orally, once daily, for 6 weeks followed by a 1-week rest
      period prior to surgery. The starting dose will be 10 mg daily with provision for dose
      reduction based on tolerability.

      Radical nephrectomy will be performed at the end of week 7. For metastatic patients, two to
      four weeks after surgery, everolimus will be reintroduced. Treatment will be continued until
      disease progression, unacceptable toxicity, withdrawal of patient consent, or other stopping
      rules are met.

      Patients with locally advanced renal carcinoma will stop drug intake before nephrectomy.

      Resumption of everolimus may be postponed in cases of a delay in wound healing or surgical
      complications.

      After treatment discontinuation and the last treatment visit (28-days after the last dose),
      patients will be followed up in order to collect data on the onset of progression and
      survival. In metastatic patients discontinuing treatment for reasons other than disease
      progression, tumor assessment will continue every 3 months, until disease progression or
      initiation of other anticancer therapy for up to one year of follow-up.
allocation: N/A
intervention model: Single Group Assignment
masking: None (Open Label)
measure: Objective clinical benefit
time frame: After 6 weeks of treatment
description: Objective clinical benefit is defined as complete response, partial response or stable disease according to RECIST criteria version 1.1
measure: Progression Free Survival
time frame: up to 1 year
measure: Overall survival
time frame: up to 2 years
measure: Safety and tolerability
time frame: Participants will be followed all along the treatment period, an expected average of 15 months
description: Toxicity will be classify according to NCI-CTC criteria Version 4.0
arm group label: everolimus
arm group type: Experimental
description: everolimus, 10 mg PO daily. Before nephrectomy: 6 continuous weeks of treatment and one week of rest After nephrectomy: 4 weeks courses (for metastatic patients only)
intervention type: Drug
intervention name: Everolimus
description: everolimus, 10 mg PO daily. Before nephrectomy: 6 continuous weeks of treatment and one week of rest After nephrectomy: 4 weeks courses (for metastatic patients only)
arm group label: everolimus
other name: AFINITOR
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Stéphane Oudard, MD, PhD
role: Principal Investigator
affiliation: Hôpital Européen Georges Pompidou, Paris (France)
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Renal Cell
mesh term: Kidney Neoplasms
mesh term: Everolimus
sharing ipd: No