<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/NCT02976272</url>
  </required_header>
  <id_info>
    <org_study_id>CHU-0291</org_study_id>
    <secondary_id>2015-A01172-47</secondary_id>
    <nct_id>NCT02976272</nct_id>
  </id_info>
  <brief_title>Neurotoxic Effect of Bortezomib Treatment in Patient With Myeloma Multiple</brief_title>
  <acronym>SENSIB</acronym>
  <official_title>Assessment of Sensory Disorders Associated With Peripheral Neuropathy Induced by Bortezomib: Prospective Comparative Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Clermont-Ferrand</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Laboratoires Takeda</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Clermont-Ferrand</source>
  <brief_summary>
    <textblock>
      Chemotherapy-induced peripheral neuropathies (CIPN) remain a problem in oncology because no&#xD;
      &quot;gold standard&quot; treatment exists to prevent or treat the CIPN. Therefore, oncologists reduce&#xD;
      or stop the chemotherapy doses to limit degradation of the quality of life of patients with&#xD;
      CIPN. Bortezomib is relatively understudied while neurotoxicity remains a limiting factor for&#xD;
      treatment. Since 2012, the FDA and the EMA validated by the administration of bortezomib&#xD;
      subcutaneously (SC) instead of intravenous (IV) in order to limit neurotoxicity.&#xD;
&#xD;
      However, a retrospective study reported that the prevalence of neuropathy induced by&#xD;
      bortezomib after SC administration remains high and equivalent to IV route. No studies have&#xD;
      quantitatively and qualitatively evaluated the sensory disorders in peripheral neuropathies&#xD;
      induced by bortezomib after SC administration. On the other hand, the QLQ-CIPN20&#xD;
      questionnaire (EORTC) evaluating the intensity of sensory, motor and autonomic disorders&#xD;
      associated with CIPN has never been tested in this population. The objective of this study is&#xD;
      twofold: (i) psychophysical evaluation of neuropathic disorders by studying the thermal and&#xD;
      vibratory detection thresholds and thermal nociceptive thresholds and (ii) quantitative and&#xD;
      qualitative assessment of neuropathic disorders by the QLQ-CIPN20 and related comorbidities&#xD;
      in a population of neuropathic patients treated with bortezomib (n = 15), compared to control&#xD;
      patients treated with bortezomib but non-neuropathic (n = 45).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Peripheral neuropathies induced by cancer chemotherapy (CIPN) remain a problem in oncology.&#xD;
      These CIPN are induced by certain classes of chemotherapy such as taxanes (paclitaxel and&#xD;
      docetaxel), platinum salts (cisplatin and oxaliplatin), alkaloids of the Madagascar&#xD;
      periwinkle (vincristine), bortezomib, thalidomide and eribulin. These CIPN is essentially&#xD;
      resulting in sensory disturbances such as paresthesia, dysesthesia or numbness.&#xD;
      Unfortunately, no treatment can be offered as &quot;gold standard&quot; for preventing or treating the&#xD;
      CIPN. Therefore, oncologists reduce or stop doses of chemotherapy because patients suffering&#xD;
      from CIPN have a marked deterioration in their quality of life and suffer from comorbidities&#xD;
      such as anxiety, depression and sleep disorders.&#xD;
&#xD;
      Among chemotherapy, bortezomib remains relatively understudied in terms of pathophysiology,&#xD;
      compared to the platinum salts or taxanes, whereas the neurotoxicity of bortezomib remains a&#xD;
      limiting factor for treatment. Currently, bortezomib is indicated for the treatment in 1st&#xD;
      line of multiple myeloma in the following protocols:&#xD;
&#xD;
        -  Patients &lt;65 years: Protocol VTD: Velcade (bortezomib), thalidomide, dexamethasone +&#xD;
           autologous transplant&#xD;
&#xD;
        -  Patients&gt; 65: Protocol MPV: Melphalan, Prednisone, Velcade. Or Protocol VD: Velcade,&#xD;
           dexamethasone Since 2012, the FDA and the EMA have validated the subcutaneous&#xD;
           administration of bortezomib instead of intravenously, in order to limit the adverse&#xD;
           effects of bortezomib, including neurotoxicity. Indeed, a large study reported that the&#xD;
           subcutaneous bortezomib allowed to keep the same therapeutic efficacy while improving&#xD;
           the safety profile and in particular by limiting peripheral neuropathies (CIPN any&#xD;
           grade: 38% vs 53%, grade ≥2: 24% vs 41%, grade ≥3 6% vs 16%). However, a recent&#xD;
           retrospective study reported that the prevalence of peripheral neuropathies induced by&#xD;
           bortezomib after subcutaneous administration remain relatively high: CIPN any grade:&#xD;
           41%, grade ≥2: 18% grade ≥3: 4 %, and especially that this prevalence of CIPN is no&#xD;
           different between subcutaneous and intravenous route.&#xD;
&#xD;
      Bortezomib is administered subcutaneously to limit the appearance of neuropathic disorders&#xD;
      and no study has evaluated quantitatively and qualitatively (QST) the sensory disorders in&#xD;
      patients with peripheral neuropathies induced by bortezomib after subcutaneous&#xD;
      administration. On the other hand, a measurement tool like the QLQ-CIPN20 questionnaire&#xD;
      (EORTC) evaluating the intensity of sensory, motor and autonomic disorders associated with&#xD;
      CIPN has never been tested in this patient population. While the questionnaire is presented&#xD;
      as the most appropriate tool in the evaluation of CIPN.&#xD;
&#xD;
      Thus, the exploration of peripheral neuropathies induced by bortezomib after subcutaneous&#xD;
      administration through QST (thermal) and QLQ-CIPN20 questionnaire would complement the&#xD;
      clinical knowledge of the CIPN. This knowledge will be essential to propose and test new&#xD;
      strategies for treatment and prevention of peripheral neuropathies induced by bortezomib.&#xD;
&#xD;
      The objective of this study is twofold: (i) psychophysical evaluation of neuropathic&#xD;
      disorders by studying the QST (thermal and vibratory sensory thresholds, thermal nociceptive&#xD;
      thresholds) and (ii) quantitative and qualitative assessment of neuropathic disorders by the&#xD;
      QLQ -CIPN20 questionnaire (EORTC) and associated comorbidities in patients treated with&#xD;
      bortezomib (subcutaneous administration).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 7, 2016</start_date>
  <completion_date type="Anticipated">January 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Thermal sensory thresholds of sensitivity to hot measured using a thermode (Medoc TSA-II Abioz Technologies)</measure>
    <time_frame>at day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Sensory thresholds of patients will be measured using a thermode (Medoc TSA-II Abioz Technologies)</measure>
    <time_frame>at day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Thermal sensory thresholds will be reviewed at the thenar eminence of 2 hands</measure>
    <time_frame>at day 1</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Sensitivity to heat, cold and vibration (will be measured using a thermode)</measure>
    <time_frame>at day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain induced by hot and cold (will be measured using a thermode)</measure>
    <time_frame>at day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuropathic symptoms (DN4 questionnaires)</measure>
    <time_frame>at day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuropathic symptoms (QLQ CIPN20 NPSI questionnaires)</measure>
    <time_frame>at day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuropathic pain (NRS) measured using a thermode (Medoc TSA-II Abioz Technologies)</measure>
    <time_frame>at day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life (QLQ-C30 questionnaires)</measure>
    <time_frame>at day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life (QLQ-MY20 questionnaires)</measure>
    <time_frame>at day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depression (HADS questionnaire)</measure>
    <time_frame>at day 1</time_frame>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Multiple Myeloma</condition>
  <condition>Bortezomib Regimen</condition>
  <condition>Adult</condition>
  <arm_group>
    <arm_group_label>patients with myeloma multiple</arm_group_label>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>bortezomib</intervention_name>
    <arm_group_label>patients with myeloma multiple</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        patients with myeloma multiple&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Multiple myeloma diagnosis.&#xD;
&#xD;
          -  Patient undergoing or who received bortezomib-based chemotherapy in first-line (VTD&#xD;
             protocol, MPV or VD).&#xD;
&#xD;
        Case Group: peripheral sensory neuropathy&#xD;
&#xD;
          -  Neuropathy ≥ grade 2 (grade 2-3) from NCI-CTCAE&#xD;
&#xD;
        Control group: asymptomatic&#xD;
&#xD;
          -  Neuropathy of grade &lt;2 (grade 0-1) from NCI-CTCAE&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt;18 years.&#xD;
&#xD;
          -  Treatment history by neurotoxic chemotherapy (taxanes, platinum salts, bortezomib,&#xD;
             thalidomide, eribulin) before the current treatment.&#xD;
&#xD;
          -  Existing treatment: opioids, tricyclic antidepressants, pregabalin, gabapentin,&#xD;
             duloxetine or AEDs.&#xD;
&#xD;
          -  Drinking: Male &gt; 3 and Woman &gt; 2 units per day.&#xD;
&#xD;
          -  Peripheral neuropathies history or known neuropathic pain&#xD;
&#xD;
          -  Progressive neurological disease.&#xD;
&#xD;
          -  Patient enrolled in a clinical study evaluating a preventive or curative treatment of&#xD;
             chemotherapy-induced peripheral neuropathy.&#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>Carine CHALETEIX</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Clermont-Ferrand</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Patrick LACARIN</last_name>
    <phone>04 73 75 11 95</phone>
    <email>placarin@chu-clermontferrand.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>CHU Clermont-Ferrand</name>
      <address>
        <city>Clermont-Ferrand</city>
        <zip>63003</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Patrick LACARIN</last_name>
      <phone>04 73 75 11 95</phone>
      <email>placarin@chu-clermontferrand.fr</email>
    </contact>
    <investigator>
      <last_name>Carine CHALETEIX</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>November 18, 2016</study_first_submitted>
  <study_first_submitted_qc>November 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>June 28, 2019</last_update_submitted>
  <last_update_submitted_qc>June 28, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 1, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bortezomib regimen</keyword>
  <keyword>patients with multiple myeloma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bortezomib</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/NCT02976272
org study id: CHU-0291
secondary id: 2015-A01172-47
nct id: NCT02976272
lead sponsor: 
collaborator: 
Chemotherapy-induced peripheral neuropathies (CIPN) remain a problem in oncology because no
      "gold standard" treatment exists to prevent or treat the CIPN. Therefore, oncologists reduce
      or stop the chemotherapy doses to limit degradation of the quality of life of patients with
      CIPN. Bortezomib is relatively understudied while neurotoxicity remains a limiting factor for
      treatment. Since 2012, the FDA and the EMA validated by the administration of bortezomib
      subcutaneously (SC) instead of intravenous (IV) in order to limit neurotoxicity.

      However, a retrospective study reported that the prevalence of neuropathy induced by
      bortezomib after SC administration remains high and equivalent to IV route. No studies have
      quantitatively and qualitatively evaluated the sensory disorders in peripheral neuropathies
      induced by bortezomib after SC administration. On the other hand, the QLQ-CIPN20
      questionnaire (EORTC) evaluating the intensity of sensory, motor and autonomic disorders
      associated with CIPN has never been tested in this population. The objective of this study is
      twofold: (i) psychophysical evaluation of neuropathic disorders by studying the thermal and
      vibratory detection thresholds and thermal nociceptive thresholds and (ii) quantitative and
      qualitative assessment of neuropathic disorders by the QLQ-CIPN20 and related comorbidities
      in a population of neuropathic patients treated with bortezomib (n = 15), compared to control
      patients treated with bortezomib but non-neuropathic (n = 45).
Peripheral neuropathies induced by cancer chemotherapy (CIPN) remain a problem in oncology.
      These CIPN are induced by certain classes of chemotherapy such as taxanes (paclitaxel and
      docetaxel), platinum salts (cisplatin and oxaliplatin), alkaloids of the Madagascar
      periwinkle (vincristine), bortezomib, thalidomide and eribulin. These CIPN is essentially
      resulting in sensory disturbances such as paresthesia, dysesthesia or numbness.
      Unfortunately, no treatment can be offered as "gold standard" for preventing or treating the
      CIPN. Therefore, oncologists reduce or stop doses of chemotherapy because patients suffering
      from CIPN have a marked deterioration in their quality of life and suffer from comorbidities
      such as anxiety, depression and sleep disorders.

      Among chemotherapy, bortezomib remains relatively understudied in terms of pathophysiology,
      compared to the platinum salts or taxanes, whereas the neurotoxicity of bortezomib remains a
      limiting factor for treatment. Currently, bortezomib is indicated for the treatment in 1st
      line of multiple myeloma in the following protocols:

        -  Patients <65 years: Protocol VTD: Velcade (bortezomib), thalidomide, dexamethasone +
           autologous transplant

        -  Patients> 65: Protocol MPV: Melphalan, Prednisone, Velcade. Or Protocol VD: Velcade,
           dexamethasone Since 2012, the FDA and the EMA have validated the subcutaneous
           administration of bortezomib instead of intravenously, in order to limit the adverse
           effects of bortezomib, including neurotoxicity. Indeed, a large study reported that the
           subcutaneous bortezomib allowed to keep the same therapeutic efficacy while improving
           the safety profile and in particular by limiting peripheral neuropathies (CIPN any
           grade: 38% vs 53%, grade ≥2: 24% vs 41%, grade ≥3 6% vs 16%). However, a recent
           retrospective study reported that the prevalence of peripheral neuropathies induced by
           bortezomib after subcutaneous administration remain relatively high: CIPN any grade:
           41%, grade ≥2: 18% grade ≥3: 4 %, and especially that this prevalence of CIPN is no
           different between subcutaneous and intravenous route.

      Bortezomib is administered subcutaneously to limit the appearance of neuropathic disorders
      and no study has evaluated quantitatively and qualitatively (QST) the sensory disorders in
      patients with peripheral neuropathies induced by bortezomib after subcutaneous
      administration. On the other hand, a measurement tool like the QLQ-CIPN20 questionnaire
      (EORTC) evaluating the intensity of sensory, motor and autonomic disorders associated with
      CIPN has never been tested in this patient population. While the questionnaire is presented
      as the most appropriate tool in the evaluation of CIPN.

      Thus, the exploration of peripheral neuropathies induced by bortezomib after subcutaneous
      administration through QST (thermal) and QLQ-CIPN20 questionnaire would complement the
      clinical knowledge of the CIPN. This knowledge will be essential to propose and test new
      strategies for treatment and prevention of peripheral neuropathies induced by bortezomib.

      The objective of this study is twofold: (i) psychophysical evaluation of neuropathic
      disorders by studying the QST (thermal and vibratory sensory thresholds, thermal nociceptive
      thresholds) and (ii) quantitative and qualitative assessment of neuropathic disorders by the
      QLQ -CIPN20 questionnaire (EORTC) and associated comorbidities in patients treated with
      bortezomib (subcutaneous administration).
observational model: Other
time perspective: Prospective
measure: Thermal sensory thresholds of sensitivity to hot measured using a thermode (Medoc TSA-II Abioz Technologies)
time frame: at day 1
measure: Sensory thresholds of patients will be measured using a thermode (Medoc TSA-II Abioz Technologies)
time frame: at day 1
measure: Thermal sensory thresholds will be reviewed at the thenar eminence of 2 hands
time frame: at day 1
measure: Sensitivity to heat, cold and vibration (will be measured using a thermode)
time frame: at day 1
measure: Pain induced by hot and cold (will be measured using a thermode)
time frame: at day 1
measure: Neuropathic symptoms (DN4 questionnaires)
time frame: at day 1
measure: Neuropathic symptoms (QLQ CIPN20 NPSI questionnaires)
time frame: at day 1
measure: Neuropathic pain (NRS) measured using a thermode (Medoc TSA-II Abioz Technologies)
time frame: at day 1
measure: Quality of life (QLQ-C30 questionnaires)
time frame: at day 1
measure: Quality of life (QLQ-MY20 questionnaires)
time frame: at day 1
measure: Depression (HADS questionnaire)
time frame: at day 1
arm group label: patients with myeloma multiple
intervention type: Other
intervention name: bortezomib
arm group label: patients with myeloma multiple
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Carine CHALETEIX
role: Principal Investigator
affiliation: University Hospital, Clermont-Ferrand
last name: Patrick LACARIN
phone: 04 73 75 11 95
email: placarin@chu-clermontferrand.fr
facility: 
status: Recruiting
contact: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Bortezomib