<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/NCT04496492</url>
  </required_header>
  <id_info>
    <org_study_id>2014-005275-92</org_study_id>
    <nct_id>NCT04496492</nct_id>
  </id_info>
  <brief_title>Preoperative Use of Tocotrienol From Annatto Bixa Orellana L. in Breast Cancer Patients: a Prospective Clinical Trial.</brief_title>
  <acronym>TOCANNATO</acronym>
  <official_title>Preoperative Use of Tocotrienol Associated With Personalized Nutritional and Psychoeducational Support in Women With Primary Breast Cancer.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</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>
      Tocotrienols have shown strong in vitro and in vivo anti-oxidant and anticancer activity,&#xD;
      promoting apoptosis and regulating oncogenic targets in breast cancer. However their clinical&#xD;
      use is still experimental especially in preoperative setting, where there are still no data&#xD;
      of antioxidant and antiinflammatory beneficial roles. This study is a prospective&#xD;
      observational clinical study enrolling 50 patients with primary breast cancer (T1-2, N0-1,&#xD;
      M0) who received 4-weeks oral treatment of delta-T3 before surgery (200 mg/twice daily) with&#xD;
      personalized nutritional and psychoeducational support. This study evaluates the effects of&#xD;
      treatment on oxidant (tock fast-Li Starfish) and antioxidant capacity (TAC Track, Li&#xD;
      Starfish), anti-inflammatory activity (complete profiling of adaptive and innate cell&#xD;
      immunity, immunologic serum markers (miRNA)), immunological response on tumor (gene&#xD;
      expression profiling on preoperative tissue tumor biopsy and on surgical specimen),&#xD;
      TNF-alpha, IL-6 and VEGF and proliferation/apoptosis, anti-inflammatory and anti-oxidant&#xD;
      activity of breast cancer cell lines.&#xD;
&#xD;
      This study evaluates the effects of treatment on oxidant (tock fast-Li Starfish) and&#xD;
      antioxidant capacity (TAC Track, Li Starfish), on anti-inflammatory activity (complete&#xD;
      profiling of adaptive and innate cell immunity, immunologic serum markers (miRNA)), on&#xD;
      immunological response on tumor (gene expression profiling on preoperative tissue tumor&#xD;
      biopsy and on surgical specimen), on TNF-alpha, IL-6 and VEGF, on proliferation/apoptosis,&#xD;
      anti-inflammatory and anti-oxidant activity of breast cancer cell lines.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      An open-label, single center, phase 2 prospective observational clinical study&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 9, 2016</start_date>
  <completion_date type="Actual">July 6, 2017</completion_date>
  <primary_completion_date type="Actual">February 9, 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in blood oxidant capacity</measure>
    <time_frame>4 weeks</time_frame>
    <description>Oxidant capacity (through tock fast-Li Starfish) (µmol/L) was measured in patients' serum samples.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in blood antioxidant capacity</measure>
    <time_frame>4 weeks</time_frame>
    <description>Antioxidant capacity (through TAC Track, Li Starfish) (µmol/L) was measured in patients' serum samples.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Absolute and relative changes in peripheral blood mononuclear cells obtained before and after four weeks of tocotrienol treatment, as detected by 13-colors citofluorimetry analysis</measure>
    <time_frame>4 weeks</time_frame>
    <description>Peripheral blood mononuclear cells were measured by 13-color cytofluorimetry analysis in patients' serum samples.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes of immune-related miRNA levels in patients' serum samples obtained before and after four weeks of tocotrienol treatment, as determined by quantitative real-time PCR analysis</measure>
    <time_frame>4 weeks</time_frame>
    <description>Immune-related miRNA levels were determined by quantitative real-time PCR analysis in patients' serum samples obtained before and after four weeks of tocotrienol treatment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in immune response associated gene levels in preoperative tissue tumor biopsies and in surgical specimens, obtained before and after four weeks of tocotrienol treatment, respectively, as determined by gene expression profiling analysis</measure>
    <time_frame>4 weeks</time_frame>
    <description>Immune response associated gene levels were determined by gene expression profiling analysis in preoperative tissue tumor biopsies and in surgical specimens, obtained before and after four weeks of tocotrienol treatment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in serum inflammatory cytokines and growth factor</measure>
    <time_frame>4 weeks</time_frame>
    <description>Blood inflammatory cytokines and growth factor (through TNF-alpha (pg/ml), IL-6 (pg/ml) and VEGF (pg/ml) quantifications) were measured in patients' serum samples</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Treatment-induced changes in proliferation/apoptosis, anti-inflammatory and anti-oxidant activity of breast cancer cell lines</measure>
    <time_frame>12,24 and 72 hours</time_frame>
    <description>Treatment-induced changes in proliferation/apoptosis, anti-inflammatory and anti-oxidant activity of breast cancer cell lines was measured through cell culture analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in expression of tumor proliferation, hormone receptors and HER2</measure>
    <time_frame>4 weeks</time_frame>
    <description>Expression of tumor proliferation index (Ki67), estrogen and/progesterone receptor and HER2 oncoprotein by IHC was determined in preoperative tumor biopsies and in surgical specimens</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Tocotrienol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects receiveTocotrienol 200 mg/twice daily before surgery</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tocotrienol</intervention_name>
    <description>Tocotrienol 200 mg orally twice a day</description>
    <arm_group_label>Tocotrienol</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  histologically confirmed operable primary breast cancer (T1-T2 N0-1 M0)&#xD;
&#xD;
          -  absence of distant metastasis&#xD;
&#xD;
          -  signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous malignancies other than in situ cervical carcinoma or nonmelanoma skin cancer&#xD;
&#xD;
          -  Breast cancer recurrence&#xD;
&#xD;
          -  Metastatic breast cancer&#xD;
&#xD;
          -  Non-epithelial breast cancer at histological examination&#xD;
&#xD;
          -  In situ lobular breast cancer&#xD;
&#xD;
          -  Participation in other randomized clinical trials that could interfere with current&#xD;
             study&#xD;
&#xD;
          -  Living distant from center and unable to attend for check-ups and meetings&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Cristina Ferraris, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fondazione IRCCS Istituto Nazionale Tumori</name>
      <address>
        <city>Milano</city>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
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  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 26, 2020</study_first_submitted>
  <study_first_submitted_qc>July 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2020</study_first_posted>
  <last_update_submitted>July 29, 2020</last_update_submitted>
  <last_update_submitted_qc>July 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </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>Tocotrienols</mesh_term>
    <mesh_term>Vitamin E</mesh_term>
    <mesh_term>Tocopherols</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/NCT04496492
org study id: 2014-005275-92
nct id: NCT04496492
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Tocotrienols have shown strong in vitro and in vivo anti-oxidant and anticancer activity,
      promoting apoptosis and regulating oncogenic targets in breast cancer. However their clinical
      use is still experimental especially in preoperative setting, where there are still no data
      of antioxidant and antiinflammatory beneficial roles. This study is a prospective
      observational clinical study enrolling 50 patients with primary breast cancer (T1-2, N0-1,
      M0) who received 4-weeks oral treatment of delta-T3 before surgery (200 mg/twice daily) with
      personalized nutritional and psychoeducational support. This study evaluates the effects of
      treatment on oxidant (tock fast-Li Starfish) and antioxidant capacity (TAC Track, Li
      Starfish), anti-inflammatory activity (complete profiling of adaptive and innate cell
      immunity, immunologic serum markers (miRNA)), immunological response on tumor (gene
      expression profiling on preoperative tissue tumor biopsy and on surgical specimen),
      TNF-alpha, IL-6 and VEGF and proliferation/apoptosis, anti-inflammatory and anti-oxidant
      activity of breast cancer cell lines.

      This study evaluates the effects of treatment on oxidant (tock fast-Li Starfish) and
      antioxidant capacity (TAC Track, Li Starfish), on anti-inflammatory activity (complete
      profiling of adaptive and innate cell immunity, immunologic serum markers (miRNA)), on
      immunological response on tumor (gene expression profiling on preoperative tissue tumor
      biopsy and on surgical specimen), on TNF-alpha, IL-6 and VEGF, on proliferation/apoptosis,
      anti-inflammatory and anti-oxidant activity of breast cancer cell lines.
An open-label, single center, phase 2 prospective observational clinical study
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Changes in blood oxidant capacity
time frame: 4 weeks
description: Oxidant capacity (through tock fast-Li Starfish) (µmol/L) was measured in patients' serum samples.
measure: Changes in blood antioxidant capacity
time frame: 4 weeks
description: Antioxidant capacity (through TAC Track, Li Starfish) (µmol/L) was measured in patients' serum samples.
measure: Absolute and relative changes in peripheral blood mononuclear cells obtained before and after four weeks of tocotrienol treatment, as detected by 13-colors citofluorimetry analysis
time frame: 4 weeks
description: Peripheral blood mononuclear cells were measured by 13-color cytofluorimetry analysis in patients' serum samples.
measure: Changes of immune-related miRNA levels in patients' serum samples obtained before and after four weeks of tocotrienol treatment, as determined by quantitative real-time PCR analysis
time frame: 4 weeks
description: Immune-related miRNA levels were determined by quantitative real-time PCR analysis in patients' serum samples obtained before and after four weeks of tocotrienol treatment
measure: Changes in immune response associated gene levels in preoperative tissue tumor biopsies and in surgical specimens, obtained before and after four weeks of tocotrienol treatment, respectively, as determined by gene expression profiling analysis
time frame: 4 weeks
description: Immune response associated gene levels were determined by gene expression profiling analysis in preoperative tissue tumor biopsies and in surgical specimens, obtained before and after four weeks of tocotrienol treatment
measure: Changes in serum inflammatory cytokines and growth factor
time frame: 4 weeks
description: Blood inflammatory cytokines and growth factor (through TNF-alpha (pg/ml), IL-6 (pg/ml) and VEGF (pg/ml) quantifications) were measured in patients' serum samples
measure: Treatment-induced changes in proliferation/apoptosis, anti-inflammatory and anti-oxidant activity of breast cancer cell lines
time frame: 12,24 and 72 hours
description: Treatment-induced changes in proliferation/apoptosis, anti-inflammatory and anti-oxidant activity of breast cancer cell lines was measured through cell culture analysis.
measure: Changes in expression of tumor proliferation, hormone receptors and HER2
time frame: 4 weeks
description: Expression of tumor proliferation index (Ki67), estrogen and/progesterone receptor and HER2 oncoprotein by IHC was determined in preoperative tumor biopsies and in surgical specimens
arm group label: Tocotrienol
arm group type: Experimental
description: Subjects receiveTocotrienol 200 mg/twice daily before surgery
intervention type: Drug
intervention name: Tocotrienol
description: Tocotrienol 200 mg orally twice a day
arm group label: Tocotrienol
criteria: 
gender: All
minimum age: 30 Years
maximum age: 65 Years
healthy volunteers: No
last name: Cristina Ferraris, MD
role: Principal Investigator
affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
facility: 
country: Italy
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responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Tocotrienols
mesh term: Vitamin E
mesh term: Tocopherols