<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/NCT02262221</url>
  </required_header>
  <id_info>
    <org_study_id>INT 48/14</org_study_id>
    <nct_id>NCT02262221</nct_id>
  </id_info>
  <brief_title>Health and Economic Outcomes of Two Different Follow up Strategies in Effectively Cured Advanced Head and Neck Cancer</brief_title>
  <acronym>HETeCo</acronym>
  <official_title>Health and Economic Outcomes of Two Different Follow up Strategies in Effectively Cured Advanced Head and Neck Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bocconi University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Pavia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Randomized, multicenter trial to evaluate the cost-effectiveness of 2 different follows up&#xD;
      programs in head and neck cancer survivors. Patients in complete remission at month 6 (+/- 1&#xD;
      month) after curative treatment will be randomized in two arms according to 2 different&#xD;
      follow up approaches: Non Intensive Follow up approach (Arm A) with no radiologic&#xD;
      evaltuations scheduled, but required only at the occurence of any signs or symptoms and&#xD;
      Intensive Follow up approach (Arm B) with scheduled radiologic evaluations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The choice about timing of follow visits for each patient will be performed before&#xD;
      randomization and will be tailored to the single patient in accordance to NCCN and AIOCC&#xD;
      guidelines following this scheduling:&#xD;
&#xD;
        -  Oral Cavity cancer: every 2 months for the 1st year, every 3 months in the 2nd year,&#xD;
           every 4 months in the 3rd year and every 6 months in the 4th and 5th year&#xD;
&#xD;
        -  Oropharyngeal and laryngeal cancer: every 3 months for the 1st and the 2nd year, every 4&#xD;
           months in the 3rd year and every 6 months in the 4th and 5th year&#xD;
&#xD;
        -  Hypopharyngeal cancer: every 3 months for the 1st and the 2nd year, every 6 months from&#xD;
           the 3rd to the 5th year&#xD;
&#xD;
      Patients deemed to be in complete remission at month 6 (+/- 1 month) after curative treatment&#xD;
      will be randomized in two follow up arms:&#xD;
&#xD;
      ARM A (Non intensive): follow up according to NCCN guidelines, consisting of outpatient&#xD;
      visits according to the schedule foreseen for single head and neck subsite. At each follow up&#xD;
      visit the patients will report all new symptoms and they will receive both physical and&#xD;
      fiberoptic endoscopic head and neck examination.&#xD;
&#xD;
      Laboratory tests (complete blood count, renal, hepatic and thyroid function) will be&#xD;
      performed once a year. Quality of life questionnaire (EuroQol 5D5L, EORTC QLQ C-30 and HN35)&#xD;
      will be administered to patients every other visit for the first 2 years and then at each&#xD;
      visit. During each visit, a socio-economic questionnaire will be also administered.&#xD;
      Locoregional imaging will be performed within 6 months after treatment end and then will be&#xD;
      recommended only on the occurrence of new signs or symptoms. Only patients in this arm will&#xD;
      be contacted by a phone call between visits in order to monitor patient's reported symptoms&#xD;
      which could be potentially related to disease recurrence.&#xD;
&#xD;
      ARM B (Intensive): follow up outpatient visits will be performed similarly to ARM A,&#xD;
      including physical and fiberoptic endoscopic head and neck evaluation and laboratory tests&#xD;
      and questionnaires. Locoregional imaging will be requested for all the patients 2 times/year&#xD;
      in the first 2 years and 1 time/year in the third and fourth year; PET scan will be requested&#xD;
      yearly in the first 3 years.&#xD;
&#xD;
      In the first year after RT end, MRI or CT scan will be performed at screening and at sixth&#xD;
      month after enrollment, while PET scan will be performed six months after enrollment.&#xD;
      Radiological imaging with PET will be customized according to smoking history being performed&#xD;
      in subjects &gt;50 years and with a smoking history of &gt; 20 pack/years.&#xD;
&#xD;
      Randomization will be stratified according to site of primary disease, smoking history (&gt;&#xD;
      10pack years) and likelihood of feasibility or non feasibility of salvage surgery if a&#xD;
      recurrence at T/N level would emerge (salvage surgery feasibility).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    Low participant accrual&#xD;
  </why_stopped>
  <start_date>June 2014</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Actual">July 2020</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>Single Group Assignment</intervention_model>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluation of the most cost-effective follow up strategy</measure>
    <time_frame>3 years</time_frame>
    <description>To evaluate the most cost-effective follow up strategy by comparing health consequences and costs of the two alternative follow-up strategies.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the percentage of potentially salvageable recurrences or second primaries</measure>
    <time_frame>3 years</time_frame>
    <description>To evaluate the percentage of potentially salvageable recurrences or second primaries in both groups of follow up approach.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the cause-specific survival</measure>
    <time_frame>3 years</time_frame>
    <description>To assess the cause-specific survival (CSS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the OS of patients recurring</measure>
    <time_frame>3 years</time_frame>
    <description>To assess the overall survival (OS) of patients recurring in both groups of follow up approach.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">330</enrollment>
  <condition>Head and Neck Cancer</condition>
  <arm_group>
    <arm_group_label>ARM A (Non intensive Follow up)</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Follow up consisting of outpatient visits according to the schedule foreseen for single head and neck subsite. At each follow up visit patients will report all new symptoms and they will receive physical and fiberoptic endoscopic head and neck examination. Laboratory tests will be performed once a year. Quality of life questionnaires will be administered to patients every other visit for the first 2 years and then at each visit. A socio-economic questionnaire will be also administered at each visit. Locoregional imaging will be performed within 6 months after radiotherapy end and recommended only at the occurrence of new signs or symptoms. Patients will be contacted by a phone call between visits in order to monitor patient's reported symptoms potentially related to disease recurrence.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ARM B (Intensive Follow up)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Intervention foreseen is scheduled radiologic evaluations (CT or MRI scan) and PET scan if patients ≥ 50 years old and with a smoking history ≥ 20 pack year. Follow up outpatient visits will be performed similarly to ARM A, including physical and fiberoptic endoscopic head and neck evaluation and laboratory tests and questionnaires. Locoregional imaging will be requested for all the patients 2 times/year in the first 2 years and 1 time/year in the third and fourth year; PET scan will be requested yearly in the first 3 years. In the first year after RT end, MRI or CT scan will be performed at screening and at sixth month after enrollment, while PET scan will be performed six months after enrollment only in patients ≥50 years and with a smoking history of ≥20 pack/years.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Scheduled radiologic evaluations</intervention_name>
    <description>Scheduled radiologic evaluations (CT or MRI scan) and PET scan in the case that patiets are ≥ 50 years old and with a smokink history ≥ 20 pack year</description>
    <arm_group_label>ARM B (Intensive Follow up)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical or pathological stage III-IV squamous cell head and neck cancer of oral&#xD;
             cavity, oropharynx, larynx or hypopharynx after curative treatment&#xD;
&#xD;
          -  Oropharyngeal cancer will be enrolled only if HPV negative or HPV positive with a&#xD;
             smoking history (i.e. greater than 10 packs/year)&#xD;
&#xD;
          -  Having already received Radiation Therapy (RT) as curative treatment or in&#xD;
             postoperative setting&#xD;
&#xD;
          -  Patients without evidence of disease within six months after treatment end (first&#xD;
             assessment of disease must be performed with radiological imaging for all patients)&#xD;
&#xD;
          -  Patient randomization must be performed at the sixth month after RT end (+/- 1 month)&#xD;
&#xD;
          -  Patients having or not received systemic treatment for a curable disease are allowed&#xD;
&#xD;
          -  Patients not considered suitable for salvage surgery (based on primary tumor&#xD;
             characteristics and previous treatments) after hypothetical recurrence are allowed;&#xD;
             the choice about feasibility or non feasibility of salvage surgery in case of&#xD;
             hypothetical recurrence at T or N level will be made by the multidisciplinary team&#xD;
             before randomization (salvage surgery score)&#xD;
&#xD;
          -  18 years or older&#xD;
&#xD;
          -  Informed consent signed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient with primary tumor site: nasopharynx, paranasal sinus, salivary gland or with&#xD;
             cancer of unknown primary in head and neck district&#xD;
&#xD;
          -  Patients unable to comply with the protocol, in the opinion of the investigator&#xD;
&#xD;
          -  Any other malignancy (except for appropriately treated superficial basal cell skin&#xD;
             cancer and surgically cured cervical cancer in situ) unless free of disease for at&#xD;
             least five years&#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>Lisa Licitra, 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 dei Tumori, Milano</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlino S. Orsola-Maplighi</name>
      <address>
        <city>Bologna</city>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spedali Civili di Brescia</name>
      <address>
        <city>Brescia</city>
        <zip>25123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Careggi</name>
      <address>
        <city>Firenze</city>
        <zip>50134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale per la ricerca sul cancro</name>
      <address>
        <city>Genova</city>
        <zip>16132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Europeo di Oncologia</name>
      <address>
        <city>Milano</city>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico di Modena</name>
      <address>
        <city>Modena</city>
        <zip>41124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale Tumori IRCCS - Fondazione Pascale</name>
      <address>
        <city>Napoli</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale di Parma</name>
      <address>
        <city>Parma</city>
        <zip>43126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Policlinico San Matteo</name>
      <address>
        <city>Pavia</city>
        <zip>27100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Santa Maria degli Angeli</name>
      <address>
        <city>Pordenone</city>
        <zip>33170</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale Tumori Regina Elena</name>
      <address>
        <city>Roma</city>
        <zip>00144</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale di Trento</name>
      <address>
        <city>Trento</city>
        <zip>38122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Oncologico della Svizzera Italiana</name>
      <address>
        <city>Bellinzona</city>
        <zip>6500</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHUV - Centre hospitalier universitaire vaudois</name>
      <address>
        <city>Lausanne</city>
        <zip>CH-1011</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>October 6, 2014</study_first_submitted>
  <study_first_submitted_qc>October 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <last_update_submitted>March 9, 2023</last_update_submitted>
  <last_update_submitted_qc>March 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 13, 2023</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>Head and Neck Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Study results will be shared trough pubblications, abstracts and posters</ipd_description>
  </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/NCT02262221
org study id: INT 48/14
nct id: NCT02262221
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Randomized, multicenter trial to evaluate the cost-effectiveness of 2 different follows up
      programs in head and neck cancer survivors. Patients in complete remission at month 6 (+/- 1
      month) after curative treatment will be randomized in two arms according to 2 different
      follow up approaches: Non Intensive Follow up approach (Arm A) with no radiologic
      evaltuations scheduled, but required only at the occurence of any signs or symptoms and
      Intensive Follow up approach (Arm B) with scheduled radiologic evaluations.
The choice about timing of follow visits for each patient will be performed before
      randomization and will be tailored to the single patient in accordance to NCCN and AIOCC
      guidelines following this scheduling:

        -  Oral Cavity cancer: every 2 months for the 1st year, every 3 months in the 2nd year,
           every 4 months in the 3rd year and every 6 months in the 4th and 5th year

        -  Oropharyngeal and laryngeal cancer: every 3 months for the 1st and the 2nd year, every 4
           months in the 3rd year and every 6 months in the 4th and 5th year

        -  Hypopharyngeal cancer: every 3 months for the 1st and the 2nd year, every 6 months from
           the 3rd to the 5th year

      Patients deemed to be in complete remission at month 6 (+/- 1 month) after curative treatment
      will be randomized in two follow up arms:

      ARM A (Non intensive): follow up according to NCCN guidelines, consisting of outpatient
      visits according to the schedule foreseen for single head and neck subsite. At each follow up
      visit the patients will report all new symptoms and they will receive both physical and
      fiberoptic endoscopic head and neck examination.

      Laboratory tests (complete blood count, renal, hepatic and thyroid function) will be
      performed once a year. Quality of life questionnaire (EuroQol 5D5L, EORTC QLQ C-30 and HN35)
      will be administered to patients every other visit for the first 2 years and then at each
      visit. During each visit, a socio-economic questionnaire will be also administered.
      Locoregional imaging will be performed within 6 months after treatment end and then will be
      recommended only on the occurrence of new signs or symptoms. Only patients in this arm will
      be contacted by a phone call between visits in order to monitor patient's reported symptoms
      which could be potentially related to disease recurrence.

      ARM B (Intensive): follow up outpatient visits will be performed similarly to ARM A,
      including physical and fiberoptic endoscopic head and neck evaluation and laboratory tests
      and questionnaires. Locoregional imaging will be requested for all the patients 2 times/year
      in the first 2 years and 1 time/year in the third and fourth year; PET scan will be requested
      yearly in the first 3 years.

      In the first year after RT end, MRI or CT scan will be performed at screening and at sixth
      month after enrollment, while PET scan will be performed six months after enrollment.
      Radiological imaging with PET will be customized according to smoking history being performed
      in subjects >50 years and with a smoking history of > 20 pack/years.

      Randomization will be stratified according to site of primary disease, smoking history (>
      10pack years) and likelihood of feasibility or non feasibility of salvage surgery if a
      recurrence at T/N level would emerge (salvage surgery feasibility).
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Health Services Research
masking: None (Open Label)
measure: Evaluation of the most cost-effective follow up strategy
time frame: 3 years
description: To evaluate the most cost-effective follow up strategy by comparing health consequences and costs of the two alternative follow-up strategies.
measure: Evaluation of the percentage of potentially salvageable recurrences or second primaries
time frame: 3 years
description: To evaluate the percentage of potentially salvageable recurrences or second primaries in both groups of follow up approach.
measure: Assessment of the cause-specific survival
time frame: 3 years
description: To assess the cause-specific survival (CSS).
measure: Assessment of the OS of patients recurring
time frame: 3 years
description: To assess the overall survival (OS) of patients recurring in both groups of follow up approach.
arm group label: ARM A (Non intensive Follow up)
arm group type: No Intervention
description: Follow up consisting of outpatient visits according to the schedule foreseen for single head and neck subsite. At each follow up visit patients will report all new symptoms and they will receive physical and fiberoptic endoscopic head and neck examination. Laboratory tests will be performed once a year. Quality of life questionnaires will be administered to patients every other visit for the first 2 years and then at each visit. A socio-economic questionnaire will be also administered at each visit. Locoregional imaging will be performed within 6 months after radiotherapy end and recommended only at the occurrence of new signs or symptoms. Patients will be contacted by a phone call between visits in order to monitor patient's reported symptoms potentially related to disease recurrence.
arm group label: ARM B (Intensive Follow up)
arm group type: Other
description: Intervention foreseen is scheduled radiologic evaluations (CT or MRI scan) and PET scan if patients ≥ 50 years old and with a smoking history ≥ 20 pack year. Follow up outpatient visits will be performed similarly to ARM A, including physical and fiberoptic endoscopic head and neck evaluation and laboratory tests and questionnaires. Locoregional imaging will be requested for all the patients 2 times/year in the first 2 years and 1 time/year in the third and fourth year; PET scan will be requested yearly in the first 3 years. In the first year after RT end, MRI or CT scan will be performed at screening and at sixth month after enrollment, while PET scan will be performed six months after enrollment only in patients ≥50 years and with a smoking history of ≥20 pack/years.
intervention type: Other
intervention name: Scheduled radiologic evaluations
description: Scheduled radiologic evaluations (CT or MRI scan) and PET scan in the case that patiets are ≥ 50 years old and with a smokink history ≥ 20 pack year
arm group label: ARM B (Intensive Follow up)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lisa Licitra, MD
role: Principal Investigator
affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Italy
country: Switzerland
responsible party type: Sponsor
mesh term: Head and Neck Neoplasms
sharing ipd: Yes
ipd description: Study results will be shared trough pubblications, abstracts and posters