<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/NCT04459234</url>
  </required_header>
  <id_info>
    <org_study_id>ET20-130 - KETACANCER</org_study_id>
    <nct_id>NCT04459234</nct_id>
  </id_info>
  <brief_title>Prospective Multicentre Study of the Use of Ketamine in the Treatment of Refractory Chronic Pain in the French CLCC</brief_title>
  <acronym>KETACANCER</acronym>
  <official_title>KETACANCER: Prospective Multicentre Study of the Use of Ketamine in the Treatment of Refractory Chronic Pain in the French CLCC</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Leon Berard</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Leon Berard</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to describe the administration practices of the&#xD;
      antalgic Ketamine in French CLCC (Centre de Lutte Contre le Cancer) in terms of indication&#xD;
      (neuropathic sequelae pains, morphine additional effect or morphine withdrawal, intensity,&#xD;
      localisation…) and administration protocol (route, posology, duration, administration&#xD;
      sequence, premedication).&#xD;
&#xD;
      The secondary objectives are to evaluate in the context of cancer, the analgesic efficacy,&#xD;
      the tolerance profile (biological and clinical toxicities) and the quality of life, including&#xD;
      anxiety and depression.&#xD;
&#xD;
      In addition, the described parameters will be evaluated as safety and efficacy predictive&#xD;
      factors of the Ketamine in oncology.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Almost 382,000 new cancers have been diagnosed in France in 2018. Regular progresses in their&#xD;
      management have improved the overall survival of patients, sometimes with sequelae that may&#xD;
      be particularly painful. Thus for 20 to 45% of patients treated for breast cancer, pain&#xD;
      persists 5 years later.&#xD;
&#xD;
      If remission is a regularly reached target, cancer was also the cause of 157,000 deaths in&#xD;
      2018 in France, preceded by months or years of progression of a chronic disease that&#xD;
      regularly causes pain. Pain during cancer (chronic cancer pain for CIM-11) remains a frequent&#xD;
      symptom, and its prevalence has slightly changed during the last 20 years.&#xD;
&#xD;
      In the European EPIC study, carried out in 2006, 76% of the cancer patients (and 62% of&#xD;
      French patients) presented moderate to severe pains linked to cancer, daily for more than&#xD;
      half of them.&#xD;
&#xD;
      Even when identified, chronic cancer pain is still under-treated in 25 to 60% of cases&#xD;
      worldwide, including in the most developed countries.&#xD;
&#xD;
      When well-managed, pain's management now allows the relief of almost 80% of patients. Pain's&#xD;
      management is based in particular on a precise and adapted use of the different opioids&#xD;
      through different routes of administration (oral, transdermal, trans-mucosal, parenteral,&#xD;
      etc.).&#xD;
&#xD;
      A neuropathic component of pain exists in almost a third of cases and may require specific&#xD;
      treatments when opioids are insufficient. In all cases, the treatment is integrated into a&#xD;
      multidisciplinary management, in connection with the ongoing oncological treatments, the&#xD;
      loco-regional treatments available (radiotherapy, interventional radiology, etc.) and with an&#xD;
      adapted psychosocial management.&#xD;
&#xD;
      Ketamine is an NMDA receptor antagonist (N-Methyl-D-Aspartate) indicated as a high dose&#xD;
      anesthetic. It is used in the context of peri-operative pain for its anti-hyperalgesic&#xD;
      properties. These properties have led to its use also in palliative care (outside the&#xD;
      marketing authorization [AMM]) to treat hyperalgesia linked to the use of high-doses of&#xD;
      opioids, as well as depression. For non-cancer pains, ketamine is widely used by centres and&#xD;
      consultations specialized in refractory chronic pain management in different pains not&#xD;
      relieved by standard treatments: neuropathic pain, fibromyalgia, etc., or even in opioids&#xD;
      weaning aid.&#xD;
&#xD;
      The bibliographic data are not homogeneous and of low quality. Despite the weakness of the&#xD;
      available data, ketamine is widely used in France in chronic pain in situation of therapeutic&#xD;
      impasse. The protocols used vary according to the prescribers and services practices: venous&#xD;
      route in general, sometimes subcutaneous or even oral; doses varying from 30 to 200 mg / day,&#xD;
      infusion duration varying from a few hours to several days, discontinuous administration by&#xD;
      cycle or continuous administration, etc.&#xD;
&#xD;
      Current knowledge is too limited in oncology to have a consensus on the use of ketamine :&#xD;
&#xD;
        -  Often retrospective studies with heterogeneous treatment protocols;&#xD;
&#xD;
        -  Studied populations also heterogeneous, with insufficiently documented indications;&#xD;
&#xD;
        -  Staff not able to answer adequately the questions raised. This situation largely&#xD;
           explains the heterogeneity of the Ketamine practices of use in oncology&#xD;
&#xD;
      It is essential to draw up an inventory of the ketamine use by the French CLCCs pain teams&#xD;
      and to identify the profile of patients in whom i) the treatment is ineffective and must be&#xD;
      avoided regarding toxicities ii) the potential efficacy required further investigations.&#xD;
      Built on a methodology close to the OKAPI study, the KETACANCER study will enable to compare&#xD;
      indirectly the results of the two studies.&#xD;
&#xD;
      To do this, it is proposed to conduct the KETACANCER prospective study in a precise&#xD;
      population defined a priori, and corresponding to the following indications:&#xD;
&#xD;
        -  Neuropathic sequelae pain&#xD;
&#xD;
        -  Additional effect of morphine&#xD;
&#xD;
        -  Morphine weaning.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 2, 2021</start_date>
  <completion_date type="Actual">March 9, 2023</completion_date>
  <primary_completion_date type="Actual">February 6, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Describe the administration practices of the antalgic Ketamine in French CLCC (Centre de Lutte Contre le Cancer) in terms of indication</measure>
    <time_frame>Up to 3 months after inclusion</time_frame>
    <description>neuropathic sequelae pains, morphine additional effect or morphine withdrawal, intensity, localisation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Describe the administration practices of the antalgic Ketamine in French CLCC (Centre de Lutte Contre le Cancer) in terms of administration protocol</measure>
    <time_frame>Up to 3 months after inclusion</time_frame>
    <description>route, posology, duration, administration sequence, premedication</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluate in the context of cancer the antalgic efficacy</measure>
    <time_frame>Up to 3 months after inclusion</time_frame>
    <description>Questionnaire: NPSI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate in the context of cancer the antalgic efficacy</measure>
    <time_frame>Up to 3 months after inclusion</time_frame>
    <description>Questionnaire: DN4</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate in the context of cancer the antalgic efficacy</measure>
    <time_frame>Up to 3 months after inclusion</time_frame>
    <description>Questionnaire: PGIC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate in the context of cancer the tolerance profile</measure>
    <time_frame>Up to 3 months after inclusion</time_frame>
    <description>The safety will be described mainly on the frequency of adverse events coded using the common toxicity criteria (NCI-CTCAE v5.0) grade. Descriptive statistics will be provided for characterizing and assessing patient's tolerance to treatment. Adverse events will be coded according to the MedDRA®.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate in the context of cancer the quality of life including anxiety and depression</measure>
    <time_frame>Up to 3 months after inclusion</time_frame>
    <description>Numeric scale (from 0 : no pain to 10: maximum pain)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate in the context of cancer the quality of life including anxiety and depression</measure>
    <time_frame>Up to 3 months after inclusion</time_frame>
    <description>Questionnaire: HADS</description>
  </secondary_outcome>
  <enrollment type="Actual">81</enrollment>
  <condition>Cancer</condition>
  <condition>Chronic Pain</condition>
  <condition>Neuropathic Pain</condition>
  <condition>Opioid Use</condition>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine use in CLCC sites (indication and administration protocol)</intervention_name>
    <description>Collection of information concerning Ketamine use by French CLCCs pain teams (first prescription):&#xD;
Indications : analgesic treatment of cancer chronic pain, analgesic treatment for a post-cancer treatment chronic pain, help for withdrawal from opioid treatment prescribed for a chronic cancer pain&#xD;
Administration protocol: route, posology, duration, administration sequence, premedication&#xD;
Antalgic efficacy&#xD;
Tolerance profile&#xD;
Quality of life, anxiety and depression evaluations</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        This is a prospective, multicentre study, considered as &quot; non-RIPH (Recherche n'Impliquant&#xD;
        pas la Personne Humaine &quot;. Indeed, the patient's participation in the study and the&#xD;
        completion of the various questionnaires has no impact on patient's safety and is not&#xD;
        likely to change his/her management. The treatment will be conducted according to the&#xD;
        standard practices of each participating site (continuous or discontinuous protocol,&#xD;
        dosage, rhythm of administration, monitoring, etc.). The questionnaires and scales used in&#xD;
        this study are part of the recommended tools for monitoring this population.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient at least 18 years old at the day of consenting to the study&#xD;
&#xD;
          -  Patient followed for a solid tumour or a hematological malignancy (treated or under&#xD;
             treatment)&#xD;
&#xD;
          -  Patient presenting cancer chronic pain or post cancer treatment pain&#xD;
&#xD;
          -  Patient followed by a CLCC's intractable chronic pain consultation or centre&#xD;
&#xD;
          -  Patient with an indication of 1st Ketamine course:&#xD;
&#xD;
          -  Analgesic treatment of cancer chronic pain&#xD;
&#xD;
          -  Analgesic treatment for a post-cancer treatment chronic pain&#xD;
&#xD;
          -  Help for withdrawal from opioid treatment prescribed for a chronic cancer pain&#xD;
&#xD;
          -  Patient not previously treated by Ketamine&#xD;
&#xD;
          -  Patient covered by a medical insurance&#xD;
&#xD;
          -  Patient and/or family did not decline data collection after complete information&#xD;
             (information sheet)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient presenting chronic pains not related to cancer or its treatments&#xD;
&#xD;
          -  Patient with a proven psychotic history&#xD;
&#xD;
          -  Patient who is not fluent enough in French&#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>Gisèle CHVETZOFF, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre Leon Berard</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institut Bergonié</name>
      <address>
        <city>Bordeaux</city>
        <zip>33076</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre François Baclesse</name>
      <address>
        <city>Caen</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Jean Perrin</name>
      <address>
        <city>Clermont-Ferrand</city>
        <zip>63011</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Leon Berard</name>
      <address>
        <city>Lyon</city>
        <zip>69008</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Paoli Calmettes</name>
      <address>
        <city>Marseille</city>
        <zip>13273</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut de Cancérologie de Montpellier</name>
      <address>
        <city>Montpellier</city>
        <zip>34298</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Curie</name>
      <address>
        <city>Paris</city>
        <zip>75005</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Godinot</name>
      <address>
        <city>Reims</city>
        <zip>51056</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Eugène Marquis</name>
      <address>
        <city>Rennes</city>
        <zip>35042</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Universitaire du Cancer (IUCT)</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut de Cancérologie de Lorraine Alexis Vautrin</name>
      <address>
        <city>Vandoeuvre les nancy</city>
        <zip>54519</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>September 8, 2023</last_update_submitted>
  <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cancer</keyword>
  <keyword>Palliative care</keyword>
  <keyword>Ketamine</keyword>
  <keyword>Chronic pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuralgia</mesh_term>
    <mesh_term>Chronic Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</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/NCT04459234
org study id: ET20-130 - KETACANCER
nct id: NCT04459234
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary objective of this study is to describe the administration practices of the
      antalgic Ketamine in French CLCC (Centre de Lutte Contre le Cancer) in terms of indication
      (neuropathic sequelae pains, morphine additional effect or morphine withdrawal, intensity,
      localisation…) and administration protocol (route, posology, duration, administration
      sequence, premedication).

      The secondary objectives are to evaluate in the context of cancer, the analgesic efficacy,
      the tolerance profile (biological and clinical toxicities) and the quality of life, including
      anxiety and depression.

      In addition, the described parameters will be evaluated as safety and efficacy predictive
      factors of the Ketamine in oncology.
Almost 382,000 new cancers have been diagnosed in France in 2018. Regular progresses in their
      management have improved the overall survival of patients, sometimes with sequelae that may
      be particularly painful. Thus for 20 to 45% of patients treated for breast cancer, pain
      persists 5 years later.

      If remission is a regularly reached target, cancer was also the cause of 157,000 deaths in
      2018 in France, preceded by months or years of progression of a chronic disease that
      regularly causes pain. Pain during cancer (chronic cancer pain for CIM-11) remains a frequent
      symptom, and its prevalence has slightly changed during the last 20 years.

      In the European EPIC study, carried out in 2006, 76% of the cancer patients (and 62% of
      French patients) presented moderate to severe pains linked to cancer, daily for more than
      half of them.

      Even when identified, chronic cancer pain is still under-treated in 25 to 60% of cases
      worldwide, including in the most developed countries.

      When well-managed, pain's management now allows the relief of almost 80% of patients. Pain's
      management is based in particular on a precise and adapted use of the different opioids
      through different routes of administration (oral, transdermal, trans-mucosal, parenteral,
      etc.).

      A neuropathic component of pain exists in almost a third of cases and may require specific
      treatments when opioids are insufficient. In all cases, the treatment is integrated into a
      multidisciplinary management, in connection with the ongoing oncological treatments, the
      loco-regional treatments available (radiotherapy, interventional radiology, etc.) and with an
      adapted psychosocial management.

      Ketamine is an NMDA receptor antagonist (N-Methyl-D-Aspartate) indicated as a high dose
      anesthetic. It is used in the context of peri-operative pain for its anti-hyperalgesic
      properties. These properties have led to its use also in palliative care (outside the
      marketing authorization [AMM]) to treat hyperalgesia linked to the use of high-doses of
      opioids, as well as depression. For non-cancer pains, ketamine is widely used by centres and
      consultations specialized in refractory chronic pain management in different pains not
      relieved by standard treatments: neuropathic pain, fibromyalgia, etc., or even in opioids
      weaning aid.

      The bibliographic data are not homogeneous and of low quality. Despite the weakness of the
      available data, ketamine is widely used in France in chronic pain in situation of therapeutic
      impasse. The protocols used vary according to the prescribers and services practices: venous
      route in general, sometimes subcutaneous or even oral; doses varying from 30 to 200 mg / day,
      infusion duration varying from a few hours to several days, discontinuous administration by
      cycle or continuous administration, etc.

      Current knowledge is too limited in oncology to have a consensus on the use of ketamine :

        -  Often retrospective studies with heterogeneous treatment protocols;

        -  Studied populations also heterogeneous, with insufficiently documented indications;

        -  Staff not able to answer adequately the questions raised. This situation largely
           explains the heterogeneity of the Ketamine practices of use in oncology

      It is essential to draw up an inventory of the ketamine use by the French CLCCs pain teams
      and to identify the profile of patients in whom i) the treatment is ineffective and must be
      avoided regarding toxicities ii) the potential efficacy required further investigations.
      Built on a methodology close to the OKAPI study, the KETACANCER study will enable to compare
      indirectly the results of the two studies.

      To do this, it is proposed to conduct the KETACANCER prospective study in a precise
      population defined a priori, and corresponding to the following indications:

        -  Neuropathic sequelae pain

        -  Additional effect of morphine

        -  Morphine weaning.
observational model: Cohort
time perspective: Prospective
measure: Describe the administration practices of the antalgic Ketamine in French CLCC (Centre de Lutte Contre le Cancer) in terms of indication
time frame: Up to 3 months after inclusion
description: neuropathic sequelae pains, morphine additional effect or morphine withdrawal, intensity, localisation
measure: Describe the administration practices of the antalgic Ketamine in French CLCC (Centre de Lutte Contre le Cancer) in terms of administration protocol
time frame: Up to 3 months after inclusion
description: route, posology, duration, administration sequence, premedication
measure: Evaluate in the context of cancer the antalgic efficacy
time frame: Up to 3 months after inclusion
description: Questionnaire: NPSI
measure: Evaluate in the context of cancer the antalgic efficacy
time frame: Up to 3 months after inclusion
description: Questionnaire: DN4
measure: Evaluate in the context of cancer the antalgic efficacy
time frame: Up to 3 months after inclusion
description: Questionnaire: PGIC
measure: Evaluate in the context of cancer the tolerance profile
time frame: Up to 3 months after inclusion
description: The safety will be described mainly on the frequency of adverse events coded using the common toxicity criteria (NCI-CTCAE v5.0) grade. Descriptive statistics will be provided for characterizing and assessing patient's tolerance to treatment. Adverse events will be coded according to the MedDRA®.
measure: Evaluate in the context of cancer the quality of life including anxiety and depression
time frame: Up to 3 months after inclusion
description: Numeric scale (from 0 : no pain to 10: maximum pain)
measure: Evaluate in the context of cancer the quality of life including anxiety and depression
time frame: Up to 3 months after inclusion
description: Questionnaire: HADS
intervention type: Drug
intervention name: Ketamine use in CLCC sites (indication and administration protocol)
description: Collection of information concerning Ketamine use by French CLCCs pain teams (first prescription):
Indications : analgesic treatment of cancer chronic pain, analgesic treatment for a post-cancer treatment chronic pain, help for withdrawal from opioid treatment prescribed for a chronic cancer pain
Administration protocol: route, posology, duration, administration sequence, premedication
Antalgic efficacy
Tolerance profile
Quality of life, anxiety and depression evaluations
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gisèle CHVETZOFF, MD
role: Principal Investigator
affiliation: Centre Leon Berard
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Neuralgia
mesh term: Chronic Pain
mesh term: Ketamine