<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/NCT03779685</url>
  </required_header>
  <id_info>
    <org_study_id>GENEXAN</org_study_id>
    <nct_id>NCT03779685</nct_id>
  </id_info>
  <brief_title>GENe EXpression After Regional or General ANesthesia in Patients Undergoing Breast Cancer Surgery</brief_title>
  <acronym>GENEXAN</acronym>
  <official_title>GENe EXpression in Tissues From Operating Field After Regional or General ANesthesia in Patients Undergoing Breast Cancer Surgery. The GENEXAN Randomized Controlled Genomic Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Azienda Ospedaliera San Gerardo di Monza</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Azienda Ospedaliera San Gerardo di Monza</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>
      Breast cancer is the most commonly diagnosed cancer in females and the second leading cause&#xD;
      of death from cancer in women. It was estimated that 2 million new cases have occurred in&#xD;
      2018 worldwide 1.&#xD;
&#xD;
      Standard anesthetic procedures for the surgery of breast cancer include general and regional&#xD;
      anesthesia 2. Growing preclinical and clinical data support the hypothesis that anesthetic&#xD;
      choice may affect cancer-related outcomes.&#xD;
&#xD;
      Recurrence in breast cancer was reduced to four-fold in a retrospective study with a 2.5 to 4&#xD;
      year follow up 3. Recurrence and metastasis-free survival, with multivariate analysis, was&#xD;
      94% (95% CI 87,100) versus 82% (74, 91) at 24 months, and 94 (87, 100) versus 77 (68, 87) at&#xD;
      36 months in the paravertebral and general anesthesia patients, respectively, (p=0.013).&#xD;
      Currently large confirmatory randomized trials evaluating breast cancer recurrence in&#xD;
      patients operated with general or regional anesthesia are yet undergoing 4.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: Exposure to general or regional anesthesia, can modulate differently breast&#xD;
      cancer biology through a direct activity on cancer cells or indirectly through modifications&#xD;
      in host response (immune system, angiogenesis, nervous system). Alterations occur both&#xD;
      systemically and locally on the surgical site and is supposed that can affect cancer-related&#xD;
      outcomes after months or years.&#xD;
&#xD;
      It is not known whether the action of this short exposure to anesthetics on the host and&#xD;
      cancer biology is driven by epigenetic alterations in gene and protein expression during the&#xD;
      immediate to early post-anesthesia period.&#xD;
&#xD;
      An altered gene and protein expression profile may affect the response of the immune system,&#xD;
      angiogenesis and the nervous system and induce more or less propitious conditions to tumor&#xD;
      progression. Data from studies in animals and humans show that gene expression may change in&#xD;
      the brain and heart after only a short exposure to general anesthesia and that changes may&#xD;
      persist for several weeks.&#xD;
&#xD;
      Methods: The GENEXAN is a randomized, controlled, monocentric, genomic trial aiming to test&#xD;
      the hypothesis that regional (paravertebral) anesthesia, compared to general anesthesia,&#xD;
      would elicit a differential gene and protein expression pattern in cancer tissue and normal&#xD;
      surgical microenvironment after breast cancer surgery in women.&#xD;
&#xD;
      Discussion: This research will serve to map gene and protein expression profile after surgery&#xD;
      with different anesthetics and elucidate which genes specific to biological systems may&#xD;
      affect tumor biology in the immediate operative period.&#xD;
&#xD;
      The findings may also address further research depending on the tissue specificity of the up&#xD;
      or down-regulated genes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">March 1, 2021</start_date>
  <completion_date type="Anticipated">March 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">March 1, 2021</primary_completion_date>
  <phase>N/A</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>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Whole genome expression by microarray</measure>
    <time_frame>before tumor excision</time_frame>
    <description>tumor, biopsy, normal wound tissue</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Whole genome expression by mircoarray</measure>
    <time_frame>during surgery (just after tumor excision)</time_frame>
    <description>tumor, wound tissue</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Immune progenitors (MDBCs, GMPs, HPSCs), Natural Killer, T regulatory Lymphocytes, PentraxinIII</measure>
    <time_frame>before tumor excision</time_frame>
    <description>in blood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cancer recurrence</measure>
    <time_frame>each 6 months for up to 7 years</time_frame>
    <description>local or distant metastasis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>survival from cancer</measure>
    <time_frame>each 6 months for up to 7 years</time_frame>
    <description>death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune progenitors (MDBCs, GMPs, HPSCs), Natural Killer, T regulatory Lymphocytes, PentraxinIII</measure>
    <time_frame>at the end of surgery</time_frame>
    <description>in blood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune progenitors (MDBCs, GMPs, HPSCs), Natural Killer, T regulatory Lymphocytes, PentraxinIII</measure>
    <time_frame>at 24 hours</time_frame>
    <description>in blood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune progenitors (MDBCs, GMPs, HPSCs), Natural Killer, T regulatory Lymphocytes, PentraxinIII</measure>
    <time_frame>at 168 hours</time_frame>
    <description>in blood</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Breast Cancer Female</condition>
  <arm_group>
    <arm_group_label>General anesthesia</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Breast cancer surgery (Tumor Stage 1-3, Nodes 0-2 as determined according to the NCI stage definitions http://www.cancer.gov/cancertopics/pdq/treatment/breast/HealthProfessional/page3/print)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Regional anesthesia</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Breast cancer surgery (Tumor Stage 1-3, Nodes 0-2 as determined according to the NCI stage definitions http://www.cancer.gov/cancertopics/pdq/treatment/breast/HealthProfessional/page3/print)</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>General anesthesia</intervention_name>
    <description>Sevoflurane and morphine</description>
    <arm_group_label>General anesthesia</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Regional anesthesia</intervention_name>
    <description>Paravertebral block</description>
    <arm_group_label>Regional anesthesia</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women 18-85 years old&#xD;
&#xD;
          -  No undergoing pregnancy&#xD;
&#xD;
          -  ASA Score I-IV&#xD;
&#xD;
          -  Patients scheduled for breast surgery&#xD;
&#xD;
          -  No contraindications (including surgical) to regional (paravertebral) anesthesia&#xD;
&#xD;
          -  No previous breast surgery&#xD;
&#xD;
          -  No known hereditary or familial cancer syndromes&#xD;
&#xD;
          -  No previous cancer anamnesis, radio o chemiotherapy&#xD;
&#xD;
          -  Primary breast cancer with Tumor classification 1-3, Nodes 0-2 as determined&#xD;
&#xD;
          -  according to the NCI stage definitions (Primary breast cancer without known extension&#xD;
             beyond the breast and axillary nodes)&#xD;
&#xD;
          -  Free from pain in preoperative period&#xD;
&#xD;
          -  Patients who don't use analgesic drugs before surgery&#xD;
&#xD;
          -  Patients without cognitive impairment or mental retardation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women &gt; 18, &lt; 85 years old&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  ASA Score &gt; IV&#xD;
&#xD;
          -  Previous breast surgery&#xD;
&#xD;
          -  Contraindications to regional anesthesia&#xD;
&#xD;
          -  Known hereditary or familial cancer syndromes&#xD;
&#xD;
          -  Previous cancer anamnesis, radio or chemiotherapy&#xD;
&#xD;
          -  Tumor classification &gt; 3, Nodes &gt; 2, M &gt; 0 as determined according to the NCI stage&#xD;
&#xD;
          -  definitions&#xD;
&#xD;
          -  Pain in preoperative period&#xD;
&#xD;
          -  Use of analgesic drugs before surgery&#xD;
&#xD;
          -  Cognitive impairment or mental retardation&#xD;
&#xD;
          -  Patients who did not gave a written informed consent&#xD;
&#xD;
          -  Undergoing therapy with alpha (doxazosin) or beta blockers.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>November 29, 2018</study_first_submitted>
  <study_first_submitted_qc>December 14, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>August 4, 2020</last_update_submitted>
  <last_update_submitted_qc>August 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Azienda Ospedaliera San Gerardo di Monza</investigator_affiliation>
    <investigator_full_name>Zhirajr Mokini M.D.</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anesthetics</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/NCT03779685
org study id: GENEXAN
nct id: NCT03779685
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Breast cancer is the most commonly diagnosed cancer in females and the second leading cause
      of death from cancer in women. It was estimated that 2 million new cases have occurred in
      2018 worldwide 1.

      Standard anesthetic procedures for the surgery of breast cancer include general and regional
      anesthesia 2. Growing preclinical and clinical data support the hypothesis that anesthetic
      choice may affect cancer-related outcomes.

      Recurrence in breast cancer was reduced to four-fold in a retrospective study with a 2.5 to 4
      year follow up 3. Recurrence and metastasis-free survival, with multivariate analysis, was
      94% (95% CI 87,100) versus 82% (74, 91) at 24 months, and 94 (87, 100) versus 77 (68, 87) at
      36 months in the paravertebral and general anesthesia patients, respectively, (p=0.013).
      Currently large confirmatory randomized trials evaluating breast cancer recurrence in
      patients operated with general or regional anesthesia are yet undergoing 4.
Background: Exposure to general or regional anesthesia, can modulate differently breast
      cancer biology through a direct activity on cancer cells or indirectly through modifications
      in host response (immune system, angiogenesis, nervous system). Alterations occur both
      systemically and locally on the surgical site and is supposed that can affect cancer-related
      outcomes after months or years.

      It is not known whether the action of this short exposure to anesthetics on the host and
      cancer biology is driven by epigenetic alterations in gene and protein expression during the
      immediate to early post-anesthesia period.

      An altered gene and protein expression profile may affect the response of the immune system,
      angiogenesis and the nervous system and induce more or less propitious conditions to tumor
      progression. Data from studies in animals and humans show that gene expression may change in
      the brain and heart after only a short exposure to general anesthesia and that changes may
      persist for several weeks.

      Methods: The GENEXAN is a randomized, controlled, monocentric, genomic trial aiming to test
      the hypothesis that regional (paravertebral) anesthesia, compared to general anesthesia,
      would elicit a differential gene and protein expression pattern in cancer tissue and normal
      surgical microenvironment after breast cancer surgery in women.

      Discussion: This research will serve to map gene and protein expression profile after surgery
      with different anesthetics and elucidate which genes specific to biological systems may
      affect tumor biology in the immediate operative period.

      The findings may also address further research depending on the tissue specificity of the up
      or down-regulated genes.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Investigator, Outcomes Assessor)
measure: Whole genome expression by microarray
time frame: before tumor excision
description: tumor, biopsy, normal wound tissue
measure: Whole genome expression by mircoarray
time frame: during surgery (just after tumor excision)
description: tumor, wound tissue
measure: Immune progenitors (MDBCs, GMPs, HPSCs), Natural Killer, T regulatory Lymphocytes, PentraxinIII
time frame: before tumor excision
description: in blood
measure: cancer recurrence
time frame: each 6 months for up to 7 years
description: local or distant metastasis
measure: survival from cancer
time frame: each 6 months for up to 7 years
description: death
measure: Immune progenitors (MDBCs, GMPs, HPSCs), Natural Killer, T regulatory Lymphocytes, PentraxinIII
time frame: at the end of surgery
description: in blood
measure: Immune progenitors (MDBCs, GMPs, HPSCs), Natural Killer, T regulatory Lymphocytes, PentraxinIII
time frame: at 24 hours
description: in blood
measure: Immune progenitors (MDBCs, GMPs, HPSCs), Natural Killer, T regulatory Lymphocytes, PentraxinIII
time frame: at 168 hours
description: in blood
arm group label: General anesthesia
arm group type: Active Comparator
description: Breast cancer surgery (Tumor Stage 1-3, Nodes 0-2 as determined according to the NCI stage definitions http://www.cancer.gov/cancertopics/pdq/treatment/breast/HealthProfessional/page3/print)
arm group label: Regional anesthesia
arm group type: Experimental
description: Breast cancer surgery (Tumor Stage 1-3, Nodes 0-2 as determined according to the NCI stage definitions http://www.cancer.gov/cancertopics/pdq/treatment/breast/HealthProfessional/page3/print)
intervention type: Procedure
intervention name: General anesthesia
description: Sevoflurane and morphine
arm group label: General anesthesia
intervention type: Procedure
intervention name: Regional anesthesia
description: Paravertebral block
arm group label: Regional anesthesia
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
responsible party type: Principal Investigator
investigator affiliation: Azienda Ospedaliera San Gerardo di Monza
investigator full name: Zhirajr Mokini M.D.
investigator title: Principal Investigator
mesh term: Breast Neoplasms
mesh term: Anesthetics
sharing ipd: No