<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/NCT03794388</url>
  </required_header>
  <id_info>
    <org_study_id>ICO-A-2018-10</org_study_id>
    <nct_id>NCT03794388</nct_id>
  </id_info>
  <brief_title>Evaluation in the Treatment of Neuropathic Pain Post Breast Surgery</brief_title>
  <acronym>CAPTRANE</acronym>
  <official_title>Multicentric, Open, Randomized Study Comparing Topical Treatment by Patch of Capsaicin to 8% (Qutenza) to Pregabalin Oral in the Early Treatment of Neuropathic Pain After Primary Surgery for Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut Cancerologie de l'Ouest</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Grünenthal GmbH</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Institut Cancerologie de l'Ouest</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Breast cancer is the most common cancer in women in Europe. Therefore, breast cancer has&#xD;
      become a chronic disease and patients need to learn to live with it as well as with the&#xD;
      adverse effects related to the disease itself or to the therapies used.&#xD;
&#xD;
      As noted in the third &quot;Plan cancer&quot;, pain is a major criterion in the quality of life of&#xD;
      patients treated for breast cancer.&#xD;
&#xD;
      Neuropathic pain was defined in 2011 by the international Association for the Study of Pain&#xD;
      (I.A.S.P.) as the direct result of a lesion or disease affecting the somato-sensory system.&#xD;
&#xD;
      Surgical treatment is often the first treatment of breast cancer. It can be conservative by&#xD;
      performing a partial mastectomy (lumpectomy or quadrantectomy) or non-preservative by total&#xD;
      mastectomy.&#xD;
&#xD;
      Intercostobrachial neuralgia (NICB) or Post mastectomy painful Syndrome (MPRR) was first&#xD;
      described by Wood in 1978 as &quot;chronic pain beginning immediately or early after a mastectomy&quot;&#xD;
      Or a lumpectomy affecting the anterior thorax, armpit and/or arm in its upper half. These&#xD;
      post-surgical pains are related to a lesion of the nerves in the breast area.&#xD;
&#xD;
      In particular, the intercostobrachial nerve can be severed, stretched or crushed during&#xD;
      surgery.&#xD;
&#xD;
      Post-operative neuropathic pain in patients with breast cancer is underdiagnosed either by&#xD;
      general practitioner or in a specialized environment.&#xD;
&#xD;
      The diagnosis of neuropathic pain is performed during examination and clinical examination.&#xD;
      Several scales allow to detect neuropathic pain but only the DN4 is recognized to be the most&#xD;
      specific and sensitive scale.&#xD;
&#xD;
      Patients do not always express this pain. They do not always reconcile with the surgery.&#xD;
      Either because the pain occurs a long time after the surgery, or they find it normal to get&#xD;
      hurt. These diagnostic difficulties cause a delay in setting up a suitable analgesic&#xD;
      treatment.&#xD;
&#xD;
      However, neuropathic pain responds poorly to common analgesics. Diagnosis, evaluation and&#xD;
      early management of neuropathic pain are a priority in order to avoid their chronicization,&#xD;
      to improve the quality of life of patients with breast cancer and to enable them to return to&#xD;
      work quickly.&#xD;
&#xD;
      We therefore assume that the diagnosis of early neuropathic pain at 2 months of surgery&#xD;
      associated with initiation of appropriate topical treatment without the systemic effects of&#xD;
      conventional oral treatments, would reduce the incidence of Chronic neuropathic pain 6 months&#xD;
      after surgery.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 19, 2019</start_date>
  <completion_date type="Actual">November 18, 2022</completion_date>
  <primary_completion_date type="Actual">November 18, 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Multicenter, open, randomized study</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To show the noninferiority of early early medical treatment by topical treatment with capsaicin compared to oral treatment of pregabalin on the evolution of neuropathic pain after 2 months in patients who have undergone surgical excision of breast cancer</measure>
    <time_frame>2 months</time_frame>
    <description>The 11-point numerical scale (0-10) is collected at 2 months.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To compare the efficacy of an early medical treatment with capsaicin topical treatment compared to oral treatment pregabalin on the evolution of neuropathic pain in patients who had undergone excision surgical breast cancer after 6 months of treatment</measure>
    <time_frame>6 months</time_frame>
    <description>The 11-point numerical scale of pain is also collected at the end of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare the functional change and quality of life perceived by patients after 2 and 6 months of treatment between the two arms: Questionnaire PGIC (patients' global impression of change)</measure>
    <time_frame>6 months</time_frame>
    <description>Questionnaire PGIC is administered to M4, M6 and at the end of treatment to measure the functional changes and quality of life changes experienced by the patient in the 2 treatment arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare the functional change and quality of life perceived by patients after 2 and 6 months of treatment between the two arms</measure>
    <time_frame>6 months</time_frame>
    <description>Questionnaire QLQ-C30 (quality of life questionnaire) is administered to M4, M6 and at the end of treatment to measure the functional changes and quality of life changes experienced by the patient in the 2 treatment arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare the functional change and quality of life perceived by patients after 2 and 6 months of treatment between the two arms</measure>
    <time_frame>6 months</time_frame>
    <description>Questionnaire EQ-5D is administered to M4, M6 and at the end of treatment to measure the functional changes and quality of life changes experienced by the patient in the 2 treatment arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Regression of the painful area after 2 and 6 months of treatment between the two arms.</measure>
    <time_frame>6 months</time_frame>
    <description>The painful area is measured from pain mapping at baseline, and after 2 months and 6 months of treatment. It is measured by the area delimited by the contours of the painful surface (centralized reading).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tolerance of each type of treatment by collecting side effects in each treatment arm.</measure>
    <time_frame>6 months</time_frame>
    <description>The tolerance of the treatments will be measured by the number of patients having at least one adverse event of grade ≥ 2 according to the classification CTCAE v5.0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients for whom only 1 application has been sufficient.</measure>
    <time_frame>6 months</time_frame>
    <description>In the capsaicin arm, the number of total patches received by the patient during the 6 months will also be counted</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact of peri-surgical anxiety and depression on the development of neuropathic pain after surgery for breast cancer</measure>
    <time_frame>49 months</time_frame>
    <description>The HAD (Hospital anxiety and despression scale) questionnaire will be collected during the screening visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of NICBs 4 months after surgery for breast cancer</measure>
    <time_frame>4 months</time_frame>
    <description>The incidence of NICBs will be measured by the number of patients included in the study (DN4 +) compared to the number of patients screened before surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The evolution of the weight between the two arms after 6 months of treatment.</measure>
    <time_frame>6 months</time_frame>
    <description>The weight is collected after 6 months of treatment</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">140</enrollment>
  <condition>Breast Cancer Patient</condition>
  <arm_group>
    <arm_group_label>Arm CAPSAICINE topical</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Application of capsaicin patches at 8% on the painful area&#xD;
1 to 2 patches will be administered during the consultation. If necessary, a second application will be realized 3 months later.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm PREGABALINE</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Pregabalin tablets will be initiated at a dose of 50 mg / day taken in 2 doses Depending on the tolerance, the dose will be increased to 100 mg / day and then to 150 mg / day to reach a maximum dose of 600 mg / day.&#xD;
An interval of 3 to 7 days must be observed between each dose increase.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capsaicin</intervention_name>
    <description>Application of capsaicin patches at 8% on painful area</description>
    <arm_group_label>Arm CAPSAICINE topical</arm_group_label>
    <other_name>qutenza EU/1/09/524/001</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pregabalin</intervention_name>
    <description>Taking Pregabalin tablets</description>
    <arm_group_label>Arm PREGABALINE</arm_group_label>
    <other_name>Lyrica</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female who had first breast cancer surgery, regardless of the type of surgery&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Healthy, non-irritated skin on painful areas to treat&#xD;
&#xD;
          -  During the inclusion visit to M4 post surgery, neuropathic pain of the breast and / or&#xD;
             axillary area corresponding to inter-brachial neuralgia with a DN4≥4 score.&#xD;
&#xD;
          -  Obtaining the signed written consent of the patient&#xD;
&#xD;
          -  Major patient affiliated to a social security scheme&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindications specific to the treatments studied : capsaicine and pregabalin&#xD;
&#xD;
          -  Diabetic patient&#xD;
&#xD;
          -  Previous treatment with capsaicin or pregabalin&#xD;
&#xD;
          -  Opioid treatment&gt; 80 mg / day (oral morphine equivalent) in progress- Topical&#xD;
             treatment of pain between surgery and inclusion visit&#xD;
&#xD;
          -  Uncontrolled hypertension (systolic blood pressure ≥ 180 mmHg or diastolic blood&#xD;
             pressure ≥ 90 mmHg) or recent history (&lt;3 months) of cardiovascular events (stroke,&#xD;
             heart attack, pulmonary embolism)&#xD;
&#xD;
          -  Creatinine clearance (CLcr) &lt;60mL / min according to the Cockcroft-Gault formula&#xD;
&#xD;
          -  Pregnant woman, likely to be pregnant or breastfeeding&#xD;
&#xD;
          -  Persons deprived of their liberty or guardianship (including curators),&#xD;
&#xD;
          -  Impossibility of submitting to the medical follow-up of the test for geographical,&#xD;
             social or psychological reasons&#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>DENIS DUPOIRON, MD</last_name>
    <role>Study Director</role>
    <affiliation>Institut de Cancérologie de l'Ouest</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institut de Cancerologie de L'Ouest</name>
      <address>
        <city>Angers</city>
        <zip>49000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Grenoble</name>
      <address>
        <city>Grenoble</city>
        <zip>38700</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chd Vendee</name>
      <address>
        <city>La Roche-sur-Yon</city>
        <zip>85025</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Oscar Lambret</name>
      <address>
        <city>Lille</city>
        <zip>59020</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Saint Vincent de Paul</name>
      <address>
        <city>Lille</city>
        <zip>59020</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>CHU NICE</name>
      <address>
        <city>Nice</city>
        <zip>06003</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Jean Godinot</name>
      <address>
        <city>Reims</city>
        <zip>51100</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Curie</name>
      <address>
        <city>Saint-Cloud</city>
        <zip>92210</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Iuct Oncopole</name>
      <address>
        <city>Toulouse</city>
        <zip>31052</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ch Valenciennes</name>
      <address>
        <city>Valenciennes</city>
        <zip>53322</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>November 5, 2018</study_first_submitted>
  <study_first_submitted_qc>January 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 7, 2019</study_first_posted>
  <last_update_submitted>July 31, 2023</last_update_submitted>
  <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Breast cancer patient</keyword>
  <keyword>Surgery</keyword>
  <keyword>Inter Costobrachial Neuralgia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Neuralgia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pregabalin</mesh_term>
    <mesh_term>Capsaicin</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/NCT03794388
org study id: ICO-A-2018-10
nct id: NCT03794388
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Breast cancer is the most common cancer in women in Europe. Therefore, breast cancer has
      become a chronic disease and patients need to learn to live with it as well as with the
      adverse effects related to the disease itself or to the therapies used.

      As noted in the third "Plan cancer", pain is a major criterion in the quality of life of
      patients treated for breast cancer.

      Neuropathic pain was defined in 2011 by the international Association for the Study of Pain
      (I.A.S.P.) as the direct result of a lesion or disease affecting the somato-sensory system.

      Surgical treatment is often the first treatment of breast cancer. It can be conservative by
      performing a partial mastectomy (lumpectomy or quadrantectomy) or non-preservative by total
      mastectomy.

      Intercostobrachial neuralgia (NICB) or Post mastectomy painful Syndrome (MPRR) was first
      described by Wood in 1978 as "chronic pain beginning immediately or early after a mastectomy"
      Or a lumpectomy affecting the anterior thorax, armpit and/or arm in its upper half. These
      post-surgical pains are related to a lesion of the nerves in the breast area.

      In particular, the intercostobrachial nerve can be severed, stretched or crushed during
      surgery.

      Post-operative neuropathic pain in patients with breast cancer is underdiagnosed either by
      general practitioner or in a specialized environment.

      The diagnosis of neuropathic pain is performed during examination and clinical examination.
      Several scales allow to detect neuropathic pain but only the DN4 is recognized to be the most
      specific and sensitive scale.

      Patients do not always express this pain. They do not always reconcile with the surgery.
      Either because the pain occurs a long time after the surgery, or they find it normal to get
      hurt. These diagnostic difficulties cause a delay in setting up a suitable analgesic
      treatment.

      However, neuropathic pain responds poorly to common analgesics. Diagnosis, evaluation and
      early management of neuropathic pain are a priority in order to avoid their chronicization,
      to improve the quality of life of patients with breast cancer and to enable them to return to
      work quickly.

      We therefore assume that the diagnosis of early neuropathic pain at 2 months of surgery
      associated with initiation of appropriate topical treatment without the systemic effects of
      conventional oral treatments, would reduce the incidence of Chronic neuropathic pain 6 months
      after surgery.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Multicenter, open, randomized study
primary purpose: Supportive Care
masking: None (Open Label)
measure: To show the noninferiority of early early medical treatment by topical treatment with capsaicin compared to oral treatment of pregabalin on the evolution of neuropathic pain after 2 months in patients who have undergone surgical excision of breast cancer
time frame: 2 months
description: The 11-point numerical scale (0-10) is collected at 2 months.
measure: To compare the efficacy of an early medical treatment with capsaicin topical treatment compared to oral treatment pregabalin on the evolution of neuropathic pain in patients who had undergone excision surgical breast cancer after 6 months of treatment
time frame: 6 months
description: The 11-point numerical scale of pain is also collected at the end of treatment
measure: To compare the functional change and quality of life perceived by patients after 2 and 6 months of treatment between the two arms: Questionnaire PGIC (patients' global impression of change)
time frame: 6 months
description: Questionnaire PGIC is administered to M4, M6 and at the end of treatment to measure the functional changes and quality of life changes experienced by the patient in the 2 treatment arms.
measure: To compare the functional change and quality of life perceived by patients after 2 and 6 months of treatment between the two arms
time frame: 6 months
description: Questionnaire QLQ-C30 (quality of life questionnaire) is administered to M4, M6 and at the end of treatment to measure the functional changes and quality of life changes experienced by the patient in the 2 treatment arms.
measure: To compare the functional change and quality of life perceived by patients after 2 and 6 months of treatment between the two arms
time frame: 6 months
description: Questionnaire EQ-5D is administered to M4, M6 and at the end of treatment to measure the functional changes and quality of life changes experienced by the patient in the 2 treatment arms.
measure: Regression of the painful area after 2 and 6 months of treatment between the two arms.
time frame: 6 months
description: The painful area is measured from pain mapping at baseline, and after 2 months and 6 months of treatment. It is measured by the area delimited by the contours of the painful surface (centralized reading).
measure: Tolerance of each type of treatment by collecting side effects in each treatment arm.
time frame: 6 months
description: The tolerance of the treatments will be measured by the number of patients having at least one adverse event of grade ≥ 2 according to the classification CTCAE v5.0.
measure: Proportion of patients for whom only 1 application has been sufficient.
time frame: 6 months
description: In the capsaicin arm, the number of total patches received by the patient during the 6 months will also be counted
measure: Impact of peri-surgical anxiety and depression on the development of neuropathic pain after surgery for breast cancer
time frame: 49 months
description: The HAD (Hospital anxiety and despression scale) questionnaire will be collected during the screening visit
measure: The incidence of NICBs 4 months after surgery for breast cancer
time frame: 4 months
description: The incidence of NICBs will be measured by the number of patients included in the study (DN4 +) compared to the number of patients screened before surgery
measure: The evolution of the weight between the two arms after 6 months of treatment.
time frame: 6 months
description: The weight is collected after 6 months of treatment
arm group label: Arm CAPSAICINE topical
arm group type: Experimental
description: Application of capsaicin patches at 8% on the painful area
1 to 2 patches will be administered during the consultation. If necessary, a second application will be realized 3 months later.
arm group label: Arm PREGABALINE
arm group type: Active Comparator
description: Pregabalin tablets will be initiated at a dose of 50 mg / day taken in 2 doses Depending on the tolerance, the dose will be increased to 100 mg / day and then to 150 mg / day to reach a maximum dose of 600 mg / day.
An interval of 3 to 7 days must be observed between each dose increase.
intervention type: Drug
intervention name: Capsaicin
description: Application of capsaicin patches at 8% on painful area
arm group label: Arm CAPSAICINE topical
other name: qutenza EU/1/09/524/001
intervention type: Drug
intervention name: Pregabalin
description: Taking Pregabalin tablets
arm group label: Arm PREGABALINE
other name: Lyrica
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: DENIS DUPOIRON, MD
role: Study Director
affiliation: Institut de Cancérologie de l'Ouest
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Neuralgia
mesh term: Pregabalin
mesh term: Capsaicin
sharing ipd: No