<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/NCT01685632</url>
  </required_header>
  <id_info>
    <org_study_id>11-PP-01</org_study_id>
    <nct_id>NCT01685632</nct_id>
  </id_info>
  <brief_title>Intra Peritoneal Chemo Hyperthermia (IPCH) : Cellular and Metabolic Consequences</brief_title>
  <acronym>CHIP</acronym>
  <official_title>Intra Peritoneal Chemo Hyperthermia (IPCH) : Cellular and Metabolic Consequences</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier Universitaire de Nice</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Hospitalier Universitaire de Nice</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Intra Peritoneal Chemo Hyperthermia (IPCH) is a recently validated option for the treatment&#xD;
      of peritoneal carcinomatosis from colorectal or ovarian origin. This therapeutic program&#xD;
      demonstrated a significant improvement of the late stages (i.e. carcinomatosis) of the&#xD;
      disease. From a clinical point of view, within the first 24 hours after IPCH, patients&#xD;
      undergo a systemic inflammatory response syndrome, and therefore require to be monitored in&#xD;
      an intensive care unit. From a metabolic perspective, preliminary data have been shown a&#xD;
      significant &quot;anaerobic style&quot; disturbance of energetic metabolism, suggesting a deep cellular&#xD;
      energetic deficit throughout IPCH process.&#xD;
&#xD;
      Putative contradictory effects of IPCH, like the increase of chemotherapy-related cellular&#xD;
      toxicity due to heat and on the other hand the initiation of a stress protein response (heat&#xD;
      shock response) which helps to reduce the cell injuries, leads to conduct a research project&#xD;
      on the underlying mechanisms: consequences, in terms of patient's care and follow-up, are of&#xD;
      high relevance.&#xD;
&#xD;
      The primary goal is a multimodal assessment of the IPCH-related cell modifications: signaling&#xD;
      pathways, apoptosis and antitumoral immune response.&#xD;
&#xD;
      The assessment criteria include Heat shock protein expression (blood/cell ratio) compared to&#xD;
      baseline values, apoptosis and immune response before/after IPCH.&#xD;
&#xD;
      The scheduled sample size is 30 patients having an IPCH and 30 patients contraindicated per&#xD;
      surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Intra Peritoneal Chemo Hyperthermia (IPCH) is a recently validated option for the treatment&#xD;
      of peritoneal carcinomatosis from colorectal or ovarian origin. This therapeutic program&#xD;
      demonstrated a significant improvement of the late stages (i.e. carcinomatosis) of the&#xD;
      disease (survival median &gt; 33 months). IPCH induces morbidity as high as 20% and mortality&#xD;
      less than 4%. From a clinical point of view, within the first 24 hours after IPCH, patients&#xD;
      undergo a systemic inflammatory response syndrome, and therefore require to be monitored in&#xD;
      an intensive care unit. From a metabolic perspective, preliminary data have been shown a&#xD;
      significant &quot;anaerobic style&quot; disturbance of energetic metabolism, suggesting a deep cellular&#xD;
      energetic deficit throughout IPCH process.&#xD;
&#xD;
      Putative contradictory effects of IPCH, like the increase of chemotherapy-related cellular&#xD;
      toxicity due to heat and on the other hand the initiation of a stress protein response (heat&#xD;
      shock response) which helps to reduce the cell injuries, leads to conduct a research project&#xD;
      on the underlying mechanisms: consequences, in terms of patient's care and follow-up, are of&#xD;
      high relevance.&#xD;
&#xD;
      Heat shock protein expression (stress protein response markers) and apoptosis are the main&#xD;
      chosen tools to evaluate IPCH-related cellular consequences.&#xD;
&#xD;
      Goals of the study Primary goal Multimodal assessment of the IPCH-related cell modifications:&#xD;
      signaling pathways, apoptosis and antitumoral immune response.&#xD;
&#xD;
      Secondary goal Comparative study of Heat shock protein expression, whether IPCH is done or&#xD;
      the patient is recused for the surgery due to intraoperative contraindication.&#xD;
&#xD;
      Method Prospective cohort follow up Procedure&#xD;
&#xD;
      Besides the usual care (surgical debulking and extensive tumoral resection after laparotomy&#xD;
      under general anesthesia), the research protocol includes :&#xD;
&#xD;
        -  7 blood samples over 72 hours (meaning less than 40 ml), including 4 samples under&#xD;
           general anesthesia throughout surgery and 3 samples during the 3 following days (at&#xD;
           24th, 48th and 72th hours).&#xD;
&#xD;
        -  6 tissue biopsies, i.e. 2 from peritoneum disease-free and 2 from invaded peritoneum ,&#xD;
           each representing a volume less than 1 cm3 and 2 biopsies from healthy colonic tissue&#xD;
           for the colon-related cancer and 4 biopsies (peritoneum n=2, tumoral tissue n=2) for&#xD;
           ovarian-related cancer. All biopsies are done during the surgery under general&#xD;
           anesthesia, and each biopsy per site before/after IPCH.&#xD;
&#xD;
      Assessment criteria&#xD;
&#xD;
        -  main criteria : Heat shock protein expression (blood/cell ratio) compared to baseline&#xD;
           values.&#xD;
&#xD;
        -  associate criteria : apoptosis and immune response before/after IPCH Statistical&#xD;
           method/Sample size/Study's lenght Scheduled sample size is 30 patients having an IPCH&#xD;
           and 30 patients contraindicated per surgery.&#xD;
&#xD;
      The normal distribution is verified using the d'Agostino-Pearson test. For intragroup&#xD;
      comparisons, the repeated measures ANOVA is done. For intergroup comparisons, an univariate&#xD;
      analysis is done, using the Student t-test and the Fisher exact test.&#xD;
&#xD;
      Taking into account the planned sample size and the annual number of IPCH, the scheduled&#xD;
      length of the study is 18 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">July 2014</completion_date>
  <primary_completion_date type="Actual">June 2014</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>heat shock protein expression (blood/cell ratio)compared to baseline values</measure>
    <time_frame>samples taken under general anesthesia throughout surgery and during the 3 following days (24h, 48h,72h)</time_frame>
    <description>7 blood samples over 72 hours (meaning less than 40 ml), including 4 samples under general anesthesia throughout surgery and 3 samples during the 3 following days (at 24th, 48th and 72th hours).&#xD;
6 tissue biopsies, i.e. 2 from peritoneum disease-free and 2 from invaded peritoneum , each representing a volume less than 1 cm3 and 2 biopsies from healthy colonic tissue for the colon-related cancer and 4 biopsies (peritoneum n=2, tumoral tissue n=2) for ovarian-related cancer. All biopsies are done during the surgery under general anesthesia, and each biopsy per site before/after IPCH.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Peritoneal Carcinomatosis From Colorectal or Ovarian Origin</condition>
  <arm_group>
    <arm_group_label>Surgery with IPCH</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients having an IPCH (Intra Peritoneal Chemo Hyperthermia) during the surgery time</description>
  </arm_group>
  <arm_group>
    <arm_group_label>patients without IPCH</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Patients recused for the surgery due to intraoperative contraindication</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Surgery with IPCH</intervention_name>
    <description>surgical debulking and extensive tumoral resection after laparotomy under general anesthesia&#xD;
7 blood samples over 72 hours, including 4 samples under general anesthesia throughout surgery and 3 samples during the 3 following days (at 24th, 48th and 72th hours).&#xD;
6 tissue biopsies, i.e. 2 from peritoneum disease-free and 2 from invaded peritoneum , each representing a volume less than 1 cm3 and 2 biopsies from healthy colonic tissue for the colon-related cancer and 4 biopsies (peritoneum n=2, tumoral tissue n=2) for ovarian-related cancer. All biopsies are done during the surgery under general anesthesia, and each biopsy per site before/after IPCH</description>
    <arm_group_label>Surgery with IPCH</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Without surgery and without IPCH</intervention_name>
    <description>The patients is opened and recused during the surgery because of extended carcinosis and closed without resection neither IPCH.&#xD;
7 blood samples over 72 hours, including 4 samples under general anesthesia throughout surgery (2 hours before IPCH, 1.5hours after IPCH, 4 hours after IPCH) and 3 samples during the 3 following days (at 24th, 48th and 72th hours).&#xD;
6 tissue biopsies, i.e. 2 from peritoneum disease-free and 2 from invaded peritoneum, each representing a volume less than 1 cm3 and 2 biopsies from healthy colonic tissue for the colon-related cancer and 4 biopsies (peritoneum n=2, tumoral tissue n=2) for ovarian-related cancer. All biopsies are done during the surgery under general anesthesia, and each biopsy per site before/after IPCH</description>
    <arm_group_label>patients without IPCH</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  adult patient&#xD;
&#xD;
          -  eligible for IPCH&#xD;
&#xD;
          -  with a social security number&#xD;
&#xD;
          -  having a signed an informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  study refusal&#xD;
&#xD;
          -  parturiants&#xD;
&#xD;
          -  psychiatric disorders&#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>Michel CARLES, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Anesthesia Department, CHU de NICE</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Département d'Anesthésie Réanimation, CHU de Nice</name>
      <address>
        <city>Nice</city>
        <zip>06200</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2015</verification_date>
  <study_first_submitted>September 12, 2012</study_first_submitted>
  <study_first_submitted_qc>September 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 14, 2012</study_first_posted>
  <last_update_submitted>October 16, 2015</last_update_submitted>
  <last_update_submitted_qc>October 16, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 19, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>intra peritonal chemo hyperthermia</keyword>
  <keyword>peritoneal carcinomatosis</keyword>
  <keyword>colorectal cancer</keyword>
  <keyword>ovarian cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Peritoneal Neoplasms</mesh_term>
    <mesh_term>Hyperthermia</mesh_term>
    <mesh_term>Fever</mesh_term>
  </condition_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/NCT01685632
org study id: 11-PP-01
nct id: NCT01685632
lead sponsor: 
has dmc: No
Intra Peritoneal Chemo Hyperthermia (IPCH) is a recently validated option for the treatment
      of peritoneal carcinomatosis from colorectal or ovarian origin. This therapeutic program
      demonstrated a significant improvement of the late stages (i.e. carcinomatosis) of the
      disease. From a clinical point of view, within the first 24 hours after IPCH, patients
      undergo a systemic inflammatory response syndrome, and therefore require to be monitored in
      an intensive care unit. From a metabolic perspective, preliminary data have been shown a
      significant "anaerobic style" disturbance of energetic metabolism, suggesting a deep cellular
      energetic deficit throughout IPCH process.

      Putative contradictory effects of IPCH, like the increase of chemotherapy-related cellular
      toxicity due to heat and on the other hand the initiation of a stress protein response (heat
      shock response) which helps to reduce the cell injuries, leads to conduct a research project
      on the underlying mechanisms: consequences, in terms of patient's care and follow-up, are of
      high relevance.

      The primary goal is a multimodal assessment of the IPCH-related cell modifications: signaling
      pathways, apoptosis and antitumoral immune response.

      The assessment criteria include Heat shock protein expression (blood/cell ratio) compared to
      baseline values, apoptosis and immune response before/after IPCH.

      The scheduled sample size is 30 patients having an IPCH and 30 patients contraindicated per
      surgery.
Intra Peritoneal Chemo Hyperthermia (IPCH) is a recently validated option for the treatment
      of peritoneal carcinomatosis from colorectal or ovarian origin. This therapeutic program
      demonstrated a significant improvement of the late stages (i.e. carcinomatosis) of the
      disease (survival median > 33 months). IPCH induces morbidity as high as 20% and mortality
      less than 4%. From a clinical point of view, within the first 24 hours after IPCH, patients
      undergo a systemic inflammatory response syndrome, and therefore require to be monitored in
      an intensive care unit. From a metabolic perspective, preliminary data have been shown a
      significant "anaerobic style" disturbance of energetic metabolism, suggesting a deep cellular
      energetic deficit throughout IPCH process.

      Putative contradictory effects of IPCH, like the increase of chemotherapy-related cellular
      toxicity due to heat and on the other hand the initiation of a stress protein response (heat
      shock response) which helps to reduce the cell injuries, leads to conduct a research project
      on the underlying mechanisms: consequences, in terms of patient's care and follow-up, are of
      high relevance.

      Heat shock protein expression (stress protein response markers) and apoptosis are the main
      chosen tools to evaluate IPCH-related cellular consequences.

      Goals of the study Primary goal Multimodal assessment of the IPCH-related cell modifications:
      signaling pathways, apoptosis and antitumoral immune response.

      Secondary goal Comparative study of Heat shock protein expression, whether IPCH is done or
      the patient is recused for the surgery due to intraoperative contraindication.

      Method Prospective cohort follow up Procedure

      Besides the usual care (surgical debulking and extensive tumoral resection after laparotomy
      under general anesthesia), the research protocol includes :

        -  7 blood samples over 72 hours (meaning less than 40 ml), including 4 samples under
           general anesthesia throughout surgery and 3 samples during the 3 following days (at
           24th, 48th and 72th hours).

        -  6 tissue biopsies, i.e. 2 from peritoneum disease-free and 2 from invaded peritoneum ,
           each representing a volume less than 1 cm3 and 2 biopsies from healthy colonic tissue
           for the colon-related cancer and 4 biopsies (peritoneum n=2, tumoral tissue n=2) for
           ovarian-related cancer. All biopsies are done during the surgery under general
           anesthesia, and each biopsy per site before/after IPCH.

      Assessment criteria

        -  main criteria : Heat shock protein expression (blood/cell ratio) compared to baseline
           values.

        -  associate criteria : apoptosis and immune response before/after IPCH Statistical
           method/Sample size/Study's lenght Scheduled sample size is 30 patients having an IPCH
           and 30 patients contraindicated per surgery.

      The normal distribution is verified using the d'Agostino-Pearson test. For intragroup
      comparisons, the repeated measures ANOVA is done. For intergroup comparisons, an univariate
      analysis is done, using the Student t-test and the Fisher exact test.

      Taking into account the planned sample size and the annual number of IPCH, the scheduled
      length of the study is 18 months.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: heat shock protein expression (blood/cell ratio)compared to baseline values
time frame: samples taken under general anesthesia throughout surgery and during the 3 following days (24h, 48h,72h)
description: 7 blood samples over 72 hours (meaning less than 40 ml), including 4 samples under general anesthesia throughout surgery and 3 samples during the 3 following days (at 24th, 48th and 72th hours).
6 tissue biopsies, i.e. 2 from peritoneum disease-free and 2 from invaded peritoneum , each representing a volume less than 1 cm3 and 2 biopsies from healthy colonic tissue for the colon-related cancer and 4 biopsies (peritoneum n=2, tumoral tissue n=2) for ovarian-related cancer. All biopsies are done during the surgery under general anesthesia, and each biopsy per site before/after IPCH.
arm group label: Surgery with IPCH
arm group type: Active Comparator
description: Patients having an IPCH (Intra Peritoneal Chemo Hyperthermia) during the surgery time
arm group label: patients without IPCH
arm group type: Sham Comparator
description: Patients recused for the surgery due to intraoperative contraindication
intervention type: Procedure
intervention name: Surgery with IPCH
description: surgical debulking and extensive tumoral resection after laparotomy under general anesthesia
7 blood samples over 72 hours, including 4 samples under general anesthesia throughout surgery and 3 samples during the 3 following days (at 24th, 48th and 72th hours).
6 tissue biopsies, i.e. 2 from peritoneum disease-free and 2 from invaded peritoneum , each representing a volume less than 1 cm3 and 2 biopsies from healthy colonic tissue for the colon-related cancer and 4 biopsies (peritoneum n=2, tumoral tissue n=2) for ovarian-related cancer. All biopsies are done during the surgery under general anesthesia, and each biopsy per site before/after IPCH
arm group label: Surgery with IPCH
intervention type: Procedure
intervention name: Without surgery and without IPCH
description: The patients is opened and recused during the surgery because of extended carcinosis and closed without resection neither IPCH.
7 blood samples over 72 hours, including 4 samples under general anesthesia throughout surgery (2 hours before IPCH, 1.5hours after IPCH, 4 hours after IPCH) and 3 samples during the 3 following days (at 24th, 48th and 72th hours).
6 tissue biopsies, i.e. 2 from peritoneum disease-free and 2 from invaded peritoneum, each representing a volume less than 1 cm3 and 2 biopsies from healthy colonic tissue for the colon-related cancer and 4 biopsies (peritoneum n=2, tumoral tissue n=2) for ovarian-related cancer. All biopsies are done during the surgery under general anesthesia, and each biopsy per site before/after IPCH
arm group label: patients without IPCH
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michel CARLES, PhD
role: Principal Investigator
affiliation: Anesthesia Department, CHU de NICE
facility: 
country: France
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Peritoneal Neoplasms
mesh term: Hyperthermia
mesh term: Fever