<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/NCT03815903</url>
  </required_header>
  <id_info>
    <org_study_id>BarretoCH - 201801</org_study_id>
    <nct_id>NCT03815903</nct_id>
  </id_info>
  <brief_title>Induction Chemotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma</brief_title>
  <acronym>INDUCTION</acronym>
  <official_title>A Phase 3, Randomized, Open-label Clinical Trial of Induction Chemotherapy Followed by Chemoradiotherapy Versus Chemoradiotherapy in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Barretos Cancer Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Barretos Cancer Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The benefit of induction chemotherapy followed by chemoradiotherapy for locally advanced head&#xD;
      and neck squamous cell carcinoma is unknown. The present study is investigating if this&#xD;
      therapeutic strategy improve overall survival.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 19, 2018</start_date>
  <completion_date type="Anticipated">December 2025</completion_date>
  <primary_completion_date type="Anticipated">December 2020</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>3-years overall survival</measure>
    <time_frame>From date of randomization until 3 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months</time_frame>
    <description>PFS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic relapse free survival</measure>
    <time_frame>From date of randomization until the date of first systemic relapse or date of death from any cause, whichever came first, assessed up to 100 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From date of randomization until the date of death from any cause, whichever came first, assessed up to 100 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate</measure>
    <time_frame>At the end of Cycle 3 of IC (each cycle is 21 days) and 8 weeks after the end of radiotherapy, through study completion, an average of 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events Rates</measure>
    <time_frame>At the end of cycle 1, cycle 2 and cycle 3 (each cycle is 21 days).</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>1-year functional organ preservation rate</measure>
    <time_frame>From date of randomization until 1 year after</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life (EORTC Quality of Life Questionnare - C30 version 3.0)</measure>
    <time_frame>From date of randomization until 5 years</time_frame>
    <description>The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate to induction chemotherapy</measure>
    <time_frame>At the end of Cycle 3 (each cycle is 21 days)</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">434</enrollment>
  <condition>Locally Advanced Malignant Neoplasm</condition>
  <arm_group>
    <arm_group_label>A - induction chemotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>B - chemoradiotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Induction chemotherapy</intervention_name>
    <description>3 cycles, each 21 days, of Cisplatin 80mg/m2 plus Paclitaxel 175mg/m2</description>
    <arm_group_label>A - induction chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Chemoradiotherapy</intervention_name>
    <description>Radiotherapy 70Gy convencional fractionation concomitant to 3 cycles, each 21 days, of Cisplatin 100mg/m2</description>
    <arm_group_label>A - induction chemotherapy</arm_group_label>
    <arm_group_label>B - chemoradiotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed histological diagnosis of squamous cell carcinoma or undifferentiated&#xD;
             carcinoma of the oropharynx, hypopharynx or larynx;&#xD;
&#xD;
          -  Locally advanced stage (stage IVa / b - AJCC 8th edition), classified as resectable **&#xD;
             or unresectable and candidate for treatment based on radiotherapy and chemotherapy;&#xD;
&#xD;
          -  Locally advanced stage (stage III - AJCC 8th edition), classified as resectable or&#xD;
             unresectable, positive p16 and candidate for treatment based on radiotherapy and&#xD;
             chemotherapy;&#xD;
&#xD;
          -  It will be allowed to include a patient with cervical lymphadenectomy if the primary&#xD;
             lesion is measurable;&#xD;
&#xD;
          -  Presence of measurable disease according to RECIST 1.1 criteria;&#xD;
&#xD;
          -  ECOG performance status of 0-1;&#xD;
&#xD;
          -  ≥ 18 years;&#xD;
&#xD;
          -  Adequate marrow reserve indicated by:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1500 / mm³ or Platelets&gt; 100,000 / mm³&#xD;
&#xD;
               -  Hemoglobin ≥ 9 g / dL - red blood cell transfusion will be allowed in the&#xD;
                  screening period if necessary&#xD;
&#xD;
          -  Adequate renal and hepatic function:&#xD;
&#xD;
               -  Serum bilirubin ≤ 1.5 times the upper limit of normal the TGO and TGP ≤ 3 upper&#xD;
                  limit of normal. If hepatic metastasis ≤ 5 upper limit of normal&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 mg / dL and creatinine clearance ≥ 60 mL / min calculated&#xD;
                  by Cockcroft-Gault.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient submitted to curative resection of the primary site and / or metastatic site.&#xD;
             NOTE: Patients submitted to cervical lymphadenectomy without surgery to the primary&#xD;
             tumor are eligible;&#xD;
&#xD;
          -  Radiation therapy or previous chemotherapy for head / neck tumor;&#xD;
&#xD;
          -  Patients with occult primary tumor;&#xD;
&#xD;
          -  T4 from any site, resectable, with invasion of cartilage or jaw;&#xD;
&#xD;
          -  History of BMT or stem cell therapy;&#xD;
&#xD;
          -  Synchronous tumor or previous history of neoplasia, except for in situ carcinoma of&#xD;
             the cervix, basal cell carcinoma or epidermoid carcinoma. Patients with previous&#xD;
             history of cancer already treated and without evidence of disease for more than 3&#xD;
             years may participate in the study;&#xD;
&#xD;
          -  Prophylactic use of G-CSF or GM-CSF two weeks prior to the study;&#xD;
&#xD;
          -  Clinically significant heart disease: unstable angina or myocardial infarction 6&#xD;
             months prior to study entry Symptomatic ventricular arrhythmia the ICC classified as&#xD;
             NYHA ≥ II • Uncontrolled hypercalcemia;&#xD;
&#xD;
          -  Uncontrolled infection;&#xD;
&#xD;
          -  Any other comorbidity that the investigator's judgment is inappropriate for the study;&#xD;
&#xD;
          -  Peripheral neuropathy&gt; grade 2;&#xD;
&#xD;
          -  Hearing loss&gt; grade 2;&#xD;
&#xD;
          -  Known positive serology for hepatitis B, hepatitis C or HIV&#xD;
&#xD;
          -  Use of antiretrovirals;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Barretos Cancer Hospital</name>
      <address>
        <city>Barretos</city>
        <state>São Paulo</state>
        <zip>14784-400</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pedro De Marchi, MD, MSc</last_name>
      <phone>+55 17 33216600</phone>
      <phone_ext>6953</phone_ext>
      <email>pedrodemarchi@yahoo.com.br</email>
    </contact>
    <contact_backup>
      <last_name>Raiany Carvalho, RN</last_name>
      <phone>+55 17 33216600</phone>
      <phone_ext>6712</phone_ext>
      <email>raiany.carvalho@hcancerbarretos.com.br</email>
    </contact_backup>
    <investigator>
      <last_name>Augusto E Mamere, MD, MSc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Alexandre A Jacinto, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Domingos Boldrini Junior, MD, MSc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Renato C Capuzzo, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Carlos R Santos, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Andre L Carvalho, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Luciano S Vianna, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Josiane D Mourão, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ricardo R Gama, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Gustavo J Dix, MD, MSc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Diogo D Prado, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Pedro De Marchi, MD, MSc</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 19, 2018</study_first_submitted>
  <study_first_submitted_qc>January 23, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>July 16, 2019</last_update_submitted>
  <last_update_submitted_qc>July 16, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 18, 2019</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>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03815903
org study id: BarretoCH - 201801
nct id: NCT03815903
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
The benefit of induction chemotherapy followed by chemoradiotherapy for locally advanced head
      and neck squamous cell carcinoma is unknown. The present study is investigating if this
      therapeutic strategy improve overall survival.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 3-years overall survival
time frame: From date of randomization until 3 years
measure: Progression free survival
time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
description: PFS
measure: Systemic relapse free survival
time frame: From date of randomization until the date of first systemic relapse or date of death from any cause, whichever came first, assessed up to 100 months
measure: Overall survival
time frame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 100 months
measure: Overall response rate
time frame: At the end of Cycle 3 of IC (each cycle is 21 days) and 8 weeks after the end of radiotherapy, through study completion, an average of 6 months
measure: Adverse Events Rates
time frame: At the end of cycle 1, cycle 2 and cycle 3 (each cycle is 21 days).
measure: 1-year functional organ preservation rate
time frame: From date of randomization until 1 year after
measure: Quality of Life (EORTC Quality of Life Questionnare - C30 version 3.0)
time frame: From date of randomization until 5 years
description: The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.
measure: Overall response rate to induction chemotherapy
time frame: At the end of Cycle 3 (each cycle is 21 days)
arm group label: A - induction chemotherapy
arm group type: Active Comparator
arm group label: B - chemoradiotherapy
arm group type: Experimental
intervention type: Drug
intervention name: Induction chemotherapy
description: 3 cycles, each 21 days, of Cisplatin 80mg/m2 plus Paclitaxel 175mg/m2
arm group label: A - induction chemotherapy
intervention type: Combination Product
intervention name: Chemoradiotherapy
description: Radiotherapy 70Gy convencional fractionation concomitant to 3 cycles, each 21 days, of Cisplatin 100mg/m2
arm group label: A - induction chemotherapy
arm group label: B - chemoradiotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Brazil
responsible party type: Sponsor
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Neoplasms
sharing ipd: Undecided