<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/NCT01695122</url>
  </required_header>
  <id_info>
    <org_study_id>327/11</org_study_id>
    <nct_id>NCT01695122</nct_id>
  </id_info>
  <brief_title>Valproic Acid and Platinum-based Chemoradiation in Locally Advanced Head and Neck Squamous Cell Carcinoma</brief_title>
  <official_title>Efficacy Evaluation of the Combination of Valproic Acid and Standard Platinum-based Chemoradiation in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Instituto do Cancer do Estado de São Paulo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Sao Paulo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Instituto do Cancer do Estado de São Paulo</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate if the addition of valproic acid to standard&#xD;
      platinum-based chemoradiation as definitive treatment of locally advanced Head and Neck&#xD;
      squamous cell carcinoma can improve treatment outcomes, such as response rate.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Valproic acid is a known histone deacetylase inhibitor. In addition to activating apoptosis&#xD;
      pathways, cell differentiation and downregulating expression of growth factors, it also&#xD;
      promotes radiosensitization.&#xD;
&#xD;
      Most patients with Head and Neck squamous cell carcinoma are diagnosed with locally advanced&#xD;
      disease, in which long term disease control is still a challenge. The incorporation of&#xD;
      epigenetic regulation into standard treatment could improve results of definitive&#xD;
      platinum-based chemoradiation in such patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">November 2014</completion_date>
  <primary_completion_date type="Actual">November 2014</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>Response Rate</measure>
    <time_frame>Within 6 to 8 weeks after completion of chemoradiation</time_frame>
    <description>RECIST v 1.1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse reactions to study treatment</measure>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>Three years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Three Years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rate comparison by p16 status</measure>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
  </secondary_outcome>
  <other_outcome>
    <measure>Biomarkers assessment</measure>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Head and Neck Cancer</condition>
  <condition>Oral Cavity Cancer</condition>
  <condition>Oropharyngeal Cancer</condition>
  <arm_group>
    <arm_group_label>valproic acid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Valproic Acid</intervention_name>
    <arm_group_label>valproic acid</arm_group_label>
    <other_name>sodium valproate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Unresectable Oropharyngeal or oral cavity squamous cell carcinoma&#xD;
&#xD;
          -  Candidate for definitive chemoradiation&#xD;
&#xD;
          -  No previous treatment&#xD;
&#xD;
          -  Measurable disease according to RECIST v 1.1&#xD;
&#xD;
          -  Previous neoplasia, other than Head and Neck, with more than five years without&#xD;
             evidence of disease; basocellular carcinoma of the skin and in situ cervical dysplasia&#xD;
             if resected&#xD;
&#xD;
          -  Age under 60 years&#xD;
&#xD;
          -  ECOG performance status 0-2&#xD;
&#xD;
          -  Ability of understanding and giving informed consent&#xD;
&#xD;
          -  Adequate renal and hepatic function&#xD;
&#xD;
          -  Adequate bone marrow function&#xD;
&#xD;
          -  Normal serum magnesium&#xD;
&#xD;
          -  Absence of QTc prolongation&#xD;
&#xD;
          -  Life expectancy of over 12 weeks&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Distant metastasis&#xD;
&#xD;
          -  Hypersensibility to valproic acid or other antiepileptic drugs&#xD;
&#xD;
          -  Valproic acid chronic use&#xD;
&#xD;
          -  Severe neurologic impairment&#xD;
&#xD;
          -  Uncontrolled comorbidity&#xD;
&#xD;
          -  Hypoalbuminemia&#xD;
&#xD;
          -  Known history of hepatitis B, C or HIV&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Milena P Mak, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Instituto do Cancer do Estado de Sao Paulo - University of Sao Paulo</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Instituto do Cancer do Estado de Sao Paulo</name>
      <address>
        <city>Sao Paulo</city>
        <state>SP</state>
        <zip>05409-011</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>February 2016</verification_date>
  <study_first_submitted>September 25, 2012</study_first_submitted>
  <study_first_submitted_qc>September 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 27, 2012</study_first_posted>
  <last_update_submitted>February 22, 2016</last_update_submitted>
  <last_update_submitted_qc>February 22, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 23, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Instituto do Cancer do Estado de São Paulo</investigator_affiliation>
    <investigator_full_name>Milena Mak</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>Head and Neck Cancer</keyword>
  <keyword>Oropharyngeal cancer</keyword>
  <keyword>Oral cavity cancer</keyword>
  <keyword>Chemoradiation</keyword>
  <keyword>valproic acid</keyword>
  <keyword>histone deacetylase</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Head and Neck Neoplasms</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
    <mesh_term>Oropharyngeal Neoplasms</mesh_term>
    <mesh_term>Mouth Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Valproic Acid</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/NCT01695122
org study id: 327/11
nct id: NCT01695122
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to evaluate if the addition of valproic acid to standard
      platinum-based chemoradiation as definitive treatment of locally advanced Head and Neck
      squamous cell carcinoma can improve treatment outcomes, such as response rate.
Valproic acid is a known histone deacetylase inhibitor. In addition to activating apoptosis
      pathways, cell differentiation and downregulating expression of growth factors, it also
      promotes radiosensitization.

      Most patients with Head and Neck squamous cell carcinoma are diagnosed with locally advanced
      disease, in which long term disease control is still a challenge. The incorporation of
      epigenetic regulation into standard treatment could improve results of definitive
      platinum-based chemoradiation in such patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Response Rate
time frame: Within 6 to 8 weeks after completion of chemoradiation
description: RECIST v 1.1
measure: Adverse reactions to study treatment
measure: Progression free survival
time frame: Three years
measure: Overall survival
time frame: Three Years
measure: Response rate comparison by p16 status
measure: Quality of life
measure: Biomarkers assessment
arm group label: valproic acid
arm group type: Experimental
intervention type: Drug
intervention name: Valproic Acid
arm group label: valproic acid
other name: sodium valproate
criteria: 
gender: All
minimum age: N/A
maximum age: 65 Years
healthy volunteers: No
last name: Milena P Mak, MD
role: Principal Investigator
affiliation: Instituto do Cancer do Estado de Sao Paulo - University of Sao Paulo
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Instituto do Cancer do Estado de São Paulo
investigator full name: Milena Mak
investigator title: MD
mesh term: Carcinoma, Squamous Cell
mesh term: Head and Neck Neoplasms
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Oropharyngeal Neoplasms
mesh term: Mouth Neoplasms
mesh term: Valproic Acid