<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/NCT03276819</url>
  </required_header>
  <id_info>
    <org_study_id>IHNPACT Umbrella</org_study_id>
    <nct_id>NCT03276819</nct_id>
  </id_info>
  <brief_title>A Clinical and Biological Umbrella Protocol for Smoker or Non-smoker Patients With OPML or HNSCC</brief_title>
  <acronym>UMBRELLA</acronym>
  <official_title>A Clinical and Biological Umbrella Protocol for Smoker or Non-smoker Patients With Oral Potentially Malignant Lesions (OPML) or Head and Neck Squamous Cell Carcinoma (HNSCC) (IHNPACT UMBRELLA)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Leon Berard</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Leon Berard</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>
      This is a multicenter minimal risk or burden prospective 3-cohort follow-up and monitoring&#xD;
      study that aims to collect clinical, socio-psychological, medico-economics data and&#xD;
      biospecimens for patients with oral potentially malignant lesions (OPML) or resectable head&#xD;
      and neck squamous cell carcinoma (HNSCC) :&#xD;
&#xD;
        -  Cohort A: OPML patients.&#xD;
&#xD;
        -  Cohort B (specific design): smokers (adults who have smoked at least 100 cigarettes in&#xD;
           their lifetime) motivated to quit - either current smokers (who currently smokes&#xD;
           cigarettes every day (daily) or some days (nondaily)) or former smokers (adults who have&#xD;
           smoked at least 100 cigarettes in their lifetime, but say they currently do not smoke)&#xD;
           who stops smoking within 3 months prior to the diagnosis - with a resectable HNSCC&#xD;
           requiring postoperative radiotherapy or chemoradiation.&#xD;
&#xD;
        -  Cohort C: Patients with resectable HNSCC non-eligible to cohort B.&#xD;
&#xD;
      The primary objective of this study is the identification of biomarkers (predictive of&#xD;
      malignant transformation or second primary tumor) and new strategies for prevention and&#xD;
      therapy, mainly through extensive genomic, epigenomic and immune characterization of OPML and&#xD;
      HNSCC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The long-term goal of this study is to reduce the incidence of HNSCC which may impact as well&#xD;
      other smoking-related cancers. It may be interesting to foster excellent translational&#xD;
      research towards the target of reducing the incidence of HNSCC by developing a global and&#xD;
      personalized approach for prevention and treatment of HNSCC. The only way to reach this goal&#xD;
      is to develop an ambitious program that coordinates the efforts of experts from various&#xD;
      fields (surgeons, medical oncologists and addictologists, scientists, sociologists and&#xD;
      economists) that will work together toward the same goal.&#xD;
&#xD;
      This study intends to gather a large scale clinical, sociological, psychological data&#xD;
      gathering combined to a unique set of biospecimens collected prospectively including oral&#xD;
      preneoplastic disease and resectable HNSCC. This represents a unique setting to develop&#xD;
      multidisciplinary studies including a translational research component (validation and&#xD;
      discovery of biomarkers, high throughput molecular studies to understand the dynamics of&#xD;
      molecular changes and identify new strategies for prevention), a sociopsychological component&#xD;
      and an addiction component that aim to increase the percentage of patients entering a process&#xD;
      of weaning, as well as a medico-economics component that intend to evaluate the impact of new&#xD;
      approaches that may emerge from our work.&#xD;
&#xD;
      In summary, this study proposes to prospectively collect clinical, sociopsychological,&#xD;
      medico-economics data and biospecimens in patients included in 3 different cohorts. Cohort A&#xD;
      will include patients with OPML, either from smokers/drinkers (S/D) or&#xD;
      non-smokers/non-drinkers (NS/ND), while cohort B and C will include patients with HNSCC&#xD;
      eligible to upfront surgical resection. Patients in cohort B will be included in an&#xD;
      interventional randomized clinical trial evaluating an intensive and sustained smoking&#xD;
      cessation program.&#xD;
&#xD;
      In patients with OPML, no standard workup and treatment plan is recommended. OPMLs biopsy is&#xD;
      important to identify patients with high grade dysplasia and in situ carcinoma who should&#xD;
      undergo surgical resection of the OMPLs if possible. Although LOH status in OPML biopsies or&#xD;
      buccal brushes has been evaluated in this population as a biomarker of risk to develop oral&#xD;
      cancer, it is not routinely performed. More studies are required to validate their value as a&#xD;
      biomarker of risk in a prospective setting and to identify the best set of biomarkers. In&#xD;
      smokers and/or excessive alcohol drinkers, it is critical to counsel and help patients quit&#xD;
      and it should be part of the standard of care. Unfortunately, this is not always the case.&#xD;
      Studies of chemopreventive agents have not resulted in the development of an intervention&#xD;
      that can be considered as standard of care.&#xD;
&#xD;
      Despite the accumulated knowledge, no comprehensive molecular characterization of OPML is&#xD;
      available. Identification of new targets for prevention and therapy, mainly with genomic,&#xD;
      epigenomic and immune characterization of OPML is critical. Cohort A will allow to&#xD;
      prospectively collect clinical information and biospecimens (biopsies, buccal brushes and&#xD;
      saliva). These unique resources will allow to confirm the value of LOH as a biomarker of risk&#xD;
      and develop standardized procedures for sample processing that can be transferred in the&#xD;
      routine setting, validate or identify other biomarkers and improve risk assessments beyond&#xD;
      LOH, to understand the spatial and temporal dynamics of molecular changes that may help&#xD;
      predicting oral cancer risk, identify relevant targets and suggest new chemoprevention&#xD;
      strategies including immunoprevention interventions. Furthermore, patients included in this&#xD;
      cohort will benefit from standardized care plans and state of the art smoking and alcohol&#xD;
      cessation programs according to current recommendations, and will be given the opportunity to&#xD;
      participate in future chemoprevention studies that may be embedded in the near future in the&#xD;
      umbrella protocol.&#xD;
&#xD;
      In patients with resectable HNSCC (cohorts B and C), smoking and alcohol cessation is one&#xD;
      important step in the management. They allow reducing treatment-related morbidity and&#xD;
      improving radiation and chemoradiation efficacy. It is tempting to believe that they may also&#xD;
      improve patients' quality of life as in the general population, and reduce the risk of second&#xD;
      primary tumor (SPT). Available data focusing on patients with HNSCC and smoking cessation is&#xD;
      scarce. Although the diagnosis and treatment of patients with HNSCC favors smoking cessation,&#xD;
      a significant proportion of former smokers are actively smoking during follow-up despite&#xD;
      having completed treatments associated with substantial morbidity. The literature review&#xD;
      shows that the range of patients that continue to smoke at one year is in the range of&#xD;
      21-41%. Of note, those smoking quit rates at one year are based on patient self-reporting&#xD;
      without biological confirmation in the majority of the cases, which clearly overestimates&#xD;
      quit rates. Smoking cessation programs currently available lead to disappointing results.&#xD;
      HNSCC patients with smoking addiction harbor the highest risk of SPTs. In this vulnerable&#xD;
      population, beyond early management of nicotine dependence, new strategies / innovative&#xD;
      interventional approaches are warranted. Preliminary results from a monocentric study&#xD;
      indicate that an active intervention in this challenging population may lead to encouraging&#xD;
      results in motivated patients. Furthermore, an intensive smoking cessation program&#xD;
      implemented during radiation therapy is feasible in this population of patients. In cohort B,&#xD;
      the efficacy of an intensive and sustained smoking cessation program in a randomized cohort&#xD;
      of these patients at highest risk with potentially curable HNSCC (cohort B) will be&#xD;
      evaluated, with the hypothesis that an intensive and sustained smoking cessation program led&#xD;
      by an addictologist or a tobacco treatment specialist (TTS) during radiation therapy may&#xD;
      improve the 6- and 12-month quite-rate compared with a minimal tobacco cessation&#xD;
      intervention. Among secondary objectives of this trial, medico-economics information will be&#xD;
      gathered to provide an initial assessment of the cost-effectiveness of the experimental&#xD;
      versus standard arms.&#xD;
&#xD;
      Cohort C will allow prospective collection of clinical information and biospecimens&#xD;
      (biopsies, buccal brushes and saliva) only. Patients will benefit from state of the art&#xD;
      smoking and alcohol cessation programs according to current recommendations.&#xD;
&#xD;
      Well-annotated cohorts of patients with HNSCC are scarce. Information and biospecimens&#xD;
      collected in cohorts B and C will provide unique resources to identify biomarkers of risk of&#xD;
      recurrence and SPT.&#xD;
&#xD;
      Having access to large scale information and to biospecimens in patients with preneoplastic&#xD;
      disease (cohort A) who may or may not develop smoking/alcohol related cancers, and with HNSCC&#xD;
      (cohorts B and C) who may develop disease recurrence or SPT, represent a unique opportunity&#xD;
      to understand the dynamics of molecular changes and their interaction with smoking cessation&#xD;
      and/or alcohol withdrawal.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Early termination of the study, since July 31, 2020 for insufficient recruitment&#xD;
  </why_stopped>
  <start_date type="Actual">February 1, 2018</start_date>
  <completion_date type="Actual">July 31, 2020</completion_date>
  <primary_completion_date type="Actual">July 31, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Cohort A : Patients with OPML Cohort B : Patients with resectable HNSCC requiring postoperative radiotherapy or chemoradiation and which are either current smokers motivated to quit or reformed smokers within 3 months before the diagnosis of a resectable HNSCC Cohort C : Patients with resectable HNSCC wich are not eligible to cohort B</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Biomarkers</measure>
    <time_frame>Month 6, Month 12, Month 24, Month 36, Month 48, Month 60 from inclusion</time_frame>
    <description>Prevalence of LOH and/or other candidate biomarkers in OPML and normal mucosa : study of their spatial and temporal dynamic changes and explore their association with the risk of developing oral cavity squamous cell carcinoma, recurrent disease or second primary tumor (blood samples, buccal biopsies, buccal cells)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>alcohol quit</measure>
    <time_frame>Month 6, Month 12, Month 24, Month 36, Month 48, Month 60 from inclusion</time_frame>
    <description>Evaluation of alcohol quit rates for addicted patients (cohorts A and C only)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>smoking quit</measure>
    <time_frame>Month 6, Month 12, Month 24, Month 36, Month 48, Month 60 from inclusion</time_frame>
    <description>Evaluation of smoking quit rates for addicted patients (cohorts A and C only)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cannabis quit</measure>
    <time_frame>Month 6, Month 12, Month 24, Month 36, Month 48, Month 60 from inclusion</time_frame>
    <description>Evaluation of cannabis quit rates for addicted patients (cohorts A and C only)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preclinical models of oral mucosa</measure>
    <time_frame>Month 6, Month 12, Month 24, Month 36, Month 48, Month 60 from inclusion</time_frame>
    <description>Patient-derived preclinical models of oral normal mucosa from smokers/drinkers and non smokers/non drinkers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preclinical models of OPML</measure>
    <time_frame>Month 6, Month 12, Month 24, Month 36, Month 48, Month 60 from inclusion</time_frame>
    <description>Patient-derived preclinical models of OPML from smokers/drinkers and non smokers/non drinkers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preclinical models of HNSCC</measure>
    <time_frame>Month 6, Month 12, Month 24, Month 36, Month 48, Month 60 from inclusion</time_frame>
    <description>Patient-derived preclinical models of HNSCC from smokers/drinkers and non smokers/non drinkers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy of intensive and sustained smoking cessation program</measure>
    <time_frame>Month 6, Month 12 after randomization</time_frame>
    <description>Evaluation of the efficacy of an experimental, intensive and sustained smoking cessation program, versus minimal tobacco cessation intervention, in helping patients with HNSCC to achieve long-term abstinence (at 12 months after randomization), middle term-abstinence (at least 6 months after randomisation) or to reduce cigarette consumption by at least 50% of baseline levels (cohort B only)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to smoking resumption</measure>
    <time_frame>Month 6, Month 12, Month 24, Month 36, Month 48, Month 60 after randomization</time_frame>
    <description>Evaluation of the time to smoking resumption (i;e; delay between randomization and smoking resumption) for the patients unable to achieve abstinence in the 2 arms (cohort B only)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life</measure>
    <time_frame>Month 6, Month 12 after randomization</time_frame>
    <description>Evaluation of the health-related quality of life using quality of life questionnaire QLQ-C30 assessment (cohort B only)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life</measure>
    <time_frame>Month 6, Month 12 after randomization</time_frame>
    <description>Evaluation of the health-related quality of life using quality of life questionnaire QLQ-H&amp;N35 assessment (cohort B only)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients' preference to the 2 smoking cessation programs</measure>
    <time_frame>Month 12 after randomization</time_frame>
    <description>Evaluation of the patients' preference by assessement of the rate of patients who refuse the intensive and sustained smoking cessation program.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Cost of the cessation program</measure>
    <time_frame>Month 12 (M12) after randomization</time_frame>
    <description>Cost of the cessation programs (Cohort B only): addictologist visits, nicotine replacement therapy, behaviorial and cognitive thérapies, psychological interventions...</description>
  </other_outcome>
  <other_outcome>
    <measure>Correlation between LOH status and smoking cessation</measure>
    <time_frame>Month 6 and month 12 (M6, M12) after randomization</time_frame>
    <description>- To analyze the LOH status at baseline (normal mucosa on resected specimen and tumor) and the dynamics of LOH changes in oral brushes (baseline, M6 and M12) to evaluate whether they may serve as a surrogate of smoking cessation (Cohort B only)</description>
  </other_outcome>
  <other_outcome>
    <measure>Prevalence of a panel of constitutional genomic variants in genes known to be associated with nicotine dependance</measure>
    <time_frame>Day 0 (at randomization)</time_frame>
    <description>Prevalence of a panel of constitutional genomic variants in genes known to be associated with nicotine dependance in patients refusing assistance for smoking cessation in comparison with patients willing to quit (Cohort B only)</description>
  </other_outcome>
  <other_outcome>
    <measure>Psychological evaluation</measure>
    <time_frame>Within 2 months after randomization</time_frame>
    <description>to determine psychological characteristics of patients, with a focus on patients who refuse assistance for smoking cessation in comparison with patients willing to quit, to decipher reasons for acceptance or refusal to enter an intensive smoking cessation program and to identify patients representations for their smoking/alcohol addiction and how patients understand their level of risk and cope/react with it (Cohort B only)</description>
  </other_outcome>
  <other_outcome>
    <measure>Sociological evaluation</measure>
    <time_frame>After randomization and Month 6 after randomization</time_frame>
    <description>to determine sociological characteristics of patients, with a focus on patients who refuse assistance for smoking cessation in comparison with patients willing to quit, to decipher reasons for acceptance or refusal to enter an intensive smoking cessation program and to identify patients representations for their smoking/alcohol addiction and how patients understand their level of risk and cope/react with it (Cohort B only)</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">53</enrollment>
  <condition>Premalignant Lesion</condition>
  <condition>Head and Neck Squamous Cell Carcinoma (HNSCC)</condition>
  <arm_group>
    <arm_group_label>Cohort A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Samples collection and Tobacco and alcohol status follow-up for patient with OPML:&#xD;
Follow-up of the lesions (pictures, biopsies, brushes), malignant transformation oversight, smoking and alcohol status follow-up (questionnaires), blood and saliva samples</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Samples collection; Psychological and Sociological evaluation; Intensive and sustained smoking cessation program; Tobacco and alcohol status follow-up for patient with resectable HNSCC requiring postoperative radiotherapy or chemoradiation and which are either current smokers motivated to quit or reformed smokers within 3 months before the diagnosis of a resectable HNSCC.&#xD;
Randomization 1:1, arm 1 = minimal tobacco cessation intervention, arm 2 = intensive and sustained smoking cessation program.&#xD;
Smoking and alcohol status follow-up, adhesion to the smoking cessation program, tumoral follow-up, second malignant lesion, tumoral collection, blood biomarkers research</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Samples collection and Tobacco and alcohol status follow-up for patients with resectable HNSCC wich are not eligible to cohort B Smoking and alcohol status follow-up (questionnaires), tumoral follow-up, second malignant lesion and OPML lesion appearance oversight, tumoral collection, blood biomarkers research</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Samples collection</intervention_name>
    <description>OPML biopsy or resection, biopsy of normal oral mucosa, surgical specimen of HNSCC, saliva samples, buccal brushes, blood samples</description>
    <arm_group_label>Cohort A</arm_group_label>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_label>Cohort C</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Psychological and Sociological evaluation</intervention_name>
    <description>Cohort B ....</description>
    <arm_group_label>Cohort B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Intensive and sustained smoking cessation program</intervention_name>
    <description>Evaluation of efficacy of the smoking cessation program (intensive and sustained versus minimal)</description>
    <arm_group_label>Cohort B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Tobacco and alcohol status follow-up</intervention_name>
    <description>Evaluation of the tobacco and alcohol status all along the study (questionnaires)</description>
    <arm_group_label>Cohort A</arm_group_label>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_label>Cohort C</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 years at the day of consenting to the study (or at the day of randomization&#xD;
             for cohort B patients not included in the global study)&#xD;
&#xD;
          2. Patients with OPML: at least one lesion ≥ 5 mm (Cohort A only)&#xD;
&#xD;
          3. Patients with surgically resectable HNSCC not treated with preoperative chemotherapy,&#xD;
             pT1-4 N0-3 M0 (Cohort B only)&#xD;
&#xD;
          4. Patients with surgically resectable HNSCC not treated with preoperative chemotherapy&#xD;
             and non-eligible to cohort B (Cohort C only)&#xD;
&#xD;
          5. PS ECOG ≤ 1&#xD;
&#xD;
          6. Treatment plan incorporating surgery and radiation therapy (or at the day of&#xD;
             randomization for cohort B patients not included in the global study)&#xD;
&#xD;
          7. Smoker = Adult who have smoked at least 100 cigarettes in his/her lifetime (Cohort B&#xD;
             only)&#xD;
&#xD;
          8. Current smoker (who currently smokes cigarettes every day (daily) or some days&#xD;
             (nondaily)) or former smoker (who says he/she doesn't smoke) who stops smoking within&#xD;
             3 months prior to diagnosis (Cohort B only)&#xD;
&#xD;
          9. Motivation to quit smoking evaluated by the Richmond test (Cohort B only)&#xD;
&#xD;
         10. Without subordination motivation to quit smoking (Cohort B only)&#xD;
&#xD;
         11. Covered by a medical insurance&#xD;
&#xD;
         12. Signed and dated informed consent document indicating that the patient has been&#xD;
             informed of all the pertinent aspects of the trial prior to enrolment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Non-stabilized cognitive disorder&#xD;
&#xD;
          2. Synchronous malignancy (Cohort A only)&#xD;
&#xD;
          3. History of malignant disease outside the upper aerodigestive tract, except skin&#xD;
             carcinoma&#xD;
&#xD;
          4. Substance use disorder other than smoking (cigarette and cannabis) and alcohol (Cohort&#xD;
             B only)&#xD;
&#xD;
          5. Use of nicotine replacement therapy, bupropion, varenicline on last 3 months (Cohort B&#xD;
             only)&#xD;
&#xD;
          6. Undergoing on last 3 months' behavioral and cognitive therapy for smoking cessation&#xD;
             (Cohort B only)&#xD;
&#xD;
          7. Patient included in a clinical trial evaluating interventions for smoking cessation&#xD;
             (Cohort B only)&#xD;
&#xD;
          8. Any psychological, familial, sociological or geographical condition potentially&#xD;
             hampering compliance with the study protocol and follow-up schedule&#xD;
&#xD;
          9. Pregnant or breastfeeding woman&#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>Pierre SAINTIGNY, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre Léon Bérard, Lyon, France</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre Hospitalier Annecy genevois</name>
      <address>
        <city>Annecy</city>
        <zip>74374</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Clermont-Ferrand</name>
      <address>
        <city>Clermont-Ferrand</city>
        <zip>63003</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Grenoble</name>
      <address>
        <city>Grenoble</city>
        <zip>38043</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Léon Bérard</name>
      <address>
        <city>Lyon</city>
        <zip>69373</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Montpellier, Hôpital Gui De Chauliac</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AP-HP, Hôpital de la Pitié Salpêtrière</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospices Civils de Lyon, Hôpital Lyon Sud</name>
      <address>
        <city>Pierre-Bénite</city>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Nancy</name>
      <address>
        <city>Vandœuvre-lès-Nancy</city>
        <zip>54511</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut de Cancérologie de Lorraine</name>
      <address>
        <city>Vandœuvre-lès-Nancy</city>
        <zip>54511</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>September 4, 2017</study_first_submitted>
  <study_first_submitted_qc>September 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 8, 2017</study_first_posted>
  <last_update_submitted>October 6, 2020</last_update_submitted>
  <last_update_submitted_qc>October 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Oral potentially malignant lesions (OPML)</keyword>
  <keyword>Head and neck squamous cell carcinoma (HNSCC)</keyword>
  <keyword>Biomarkers</keyword>
  <keyword>Smoking cessation program</keyword>
  <keyword>Loss of heterozigoty (LOH)</keyword>
  <keyword>Medico-economics</keyword>
  <keyword>Sociology</keyword>
  <keyword>Psychology</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
    <mesh_term>Precancerous Conditions</mesh_term>
  </condition_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/NCT03276819
org study id: IHNPACT Umbrella
nct id: NCT03276819
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a multicenter minimal risk or burden prospective 3-cohort follow-up and monitoring
      study that aims to collect clinical, socio-psychological, medico-economics data and
      biospecimens for patients with oral potentially malignant lesions (OPML) or resectable head
      and neck squamous cell carcinoma (HNSCC) :

        -  Cohort A: OPML patients.

        -  Cohort B (specific design): smokers (adults who have smoked at least 100 cigarettes in
           their lifetime) motivated to quit - either current smokers (who currently smokes
           cigarettes every day (daily) or some days (nondaily)) or former smokers (adults who have
           smoked at least 100 cigarettes in their lifetime, but say they currently do not smoke)
           who stops smoking within 3 months prior to the diagnosis - with a resectable HNSCC
           requiring postoperative radiotherapy or chemoradiation.

        -  Cohort C: Patients with resectable HNSCC non-eligible to cohort B.

      The primary objective of this study is the identification of biomarkers (predictive of
      malignant transformation or second primary tumor) and new strategies for prevention and
      therapy, mainly through extensive genomic, epigenomic and immune characterization of OPML and
      HNSCC.
The long-term goal of this study is to reduce the incidence of HNSCC which may impact as well
      other smoking-related cancers. It may be interesting to foster excellent translational
      research towards the target of reducing the incidence of HNSCC by developing a global and
      personalized approach for prevention and treatment of HNSCC. The only way to reach this goal
      is to develop an ambitious program that coordinates the efforts of experts from various
      fields (surgeons, medical oncologists and addictologists, scientists, sociologists and
      economists) that will work together toward the same goal.

      This study intends to gather a large scale clinical, sociological, psychological data
      gathering combined to a unique set of biospecimens collected prospectively including oral
      preneoplastic disease and resectable HNSCC. This represents a unique setting to develop
      multidisciplinary studies including a translational research component (validation and
      discovery of biomarkers, high throughput molecular studies to understand the dynamics of
      molecular changes and identify new strategies for prevention), a sociopsychological component
      and an addiction component that aim to increase the percentage of patients entering a process
      of weaning, as well as a medico-economics component that intend to evaluate the impact of new
      approaches that may emerge from our work.

      In summary, this study proposes to prospectively collect clinical, sociopsychological,
      medico-economics data and biospecimens in patients included in 3 different cohorts. Cohort A
      will include patients with OPML, either from smokers/drinkers (S/D) or
      non-smokers/non-drinkers (NS/ND), while cohort B and C will include patients with HNSCC
      eligible to upfront surgical resection. Patients in cohort B will be included in an
      interventional randomized clinical trial evaluating an intensive and sustained smoking
      cessation program.

      In patients with OPML, no standard workup and treatment plan is recommended. OPMLs biopsy is
      important to identify patients with high grade dysplasia and in situ carcinoma who should
      undergo surgical resection of the OMPLs if possible. Although LOH status in OPML biopsies or
      buccal brushes has been evaluated in this population as a biomarker of risk to develop oral
      cancer, it is not routinely performed. More studies are required to validate their value as a
      biomarker of risk in a prospective setting and to identify the best set of biomarkers. In
      smokers and/or excessive alcohol drinkers, it is critical to counsel and help patients quit
      and it should be part of the standard of care. Unfortunately, this is not always the case.
      Studies of chemopreventive agents have not resulted in the development of an intervention
      that can be considered as standard of care.

      Despite the accumulated knowledge, no comprehensive molecular characterization of OPML is
      available. Identification of new targets for prevention and therapy, mainly with genomic,
      epigenomic and immune characterization of OPML is critical. Cohort A will allow to
      prospectively collect clinical information and biospecimens (biopsies, buccal brushes and
      saliva). These unique resources will allow to confirm the value of LOH as a biomarker of risk
      and develop standardized procedures for sample processing that can be transferred in the
      routine setting, validate or identify other biomarkers and improve risk assessments beyond
      LOH, to understand the spatial and temporal dynamics of molecular changes that may help
      predicting oral cancer risk, identify relevant targets and suggest new chemoprevention
      strategies including immunoprevention interventions. Furthermore, patients included in this
      cohort will benefit from standardized care plans and state of the art smoking and alcohol
      cessation programs according to current recommendations, and will be given the opportunity to
      participate in future chemoprevention studies that may be embedded in the near future in the
      umbrella protocol.

      In patients with resectable HNSCC (cohorts B and C), smoking and alcohol cessation is one
      important step in the management. They allow reducing treatment-related morbidity and
      improving radiation and chemoradiation efficacy. It is tempting to believe that they may also
      improve patients' quality of life as in the general population, and reduce the risk of second
      primary tumor (SPT). Available data focusing on patients with HNSCC and smoking cessation is
      scarce. Although the diagnosis and treatment of patients with HNSCC favors smoking cessation,
      a significant proportion of former smokers are actively smoking during follow-up despite
      having completed treatments associated with substantial morbidity. The literature review
      shows that the range of patients that continue to smoke at one year is in the range of
      21-41%. Of note, those smoking quit rates at one year are based on patient self-reporting
      without biological confirmation in the majority of the cases, which clearly overestimates
      quit rates. Smoking cessation programs currently available lead to disappointing results.
      HNSCC patients with smoking addiction harbor the highest risk of SPTs. In this vulnerable
      population, beyond early management of nicotine dependence, new strategies / innovative
      interventional approaches are warranted. Preliminary results from a monocentric study
      indicate that an active intervention in this challenging population may lead to encouraging
      results in motivated patients. Furthermore, an intensive smoking cessation program
      implemented during radiation therapy is feasible in this population of patients. In cohort B,
      the efficacy of an intensive and sustained smoking cessation program in a randomized cohort
      of these patients at highest risk with potentially curable HNSCC (cohort B) will be
      evaluated, with the hypothesis that an intensive and sustained smoking cessation program led
      by an addictologist or a tobacco treatment specialist (TTS) during radiation therapy may
      improve the 6- and 12-month quite-rate compared with a minimal tobacco cessation
      intervention. Among secondary objectives of this trial, medico-economics information will be
      gathered to provide an initial assessment of the cost-effectiveness of the experimental
      versus standard arms.

      Cohort C will allow prospective collection of clinical information and biospecimens
      (biopsies, buccal brushes and saliva) only. Patients will benefit from state of the art
      smoking and alcohol cessation programs according to current recommendations.

      Well-annotated cohorts of patients with HNSCC are scarce. Information and biospecimens
      collected in cohorts B and C will provide unique resources to identify biomarkers of risk of
      recurrence and SPT.

      Having access to large scale information and to biospecimens in patients with preneoplastic
      disease (cohort A) who may or may not develop smoking/alcohol related cancers, and with HNSCC
      (cohorts B and C) who may develop disease recurrence or SPT, represent a unique opportunity
      to understand the dynamics of molecular changes and their interaction with smoking cessation
      and/or alcohol withdrawal.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Cohort A : Patients with OPML Cohort B : Patients with resectable HNSCC requiring postoperative radiotherapy or chemoradiation and which are either current smokers motivated to quit or reformed smokers within 3 months before the diagnosis of a resectable HNSCC Cohort C : Patients with resectable HNSCC wich are not eligible to cohort B
primary purpose: Prevention
masking: None (Open Label)
measure: Biomarkers
time frame: Month 6, Month 12, Month 24, Month 36, Month 48, Month 60 from inclusion
description: Prevalence of LOH and/or other candidate biomarkers in OPML and normal mucosa : study of their spatial and temporal dynamic changes and explore their association with the risk of developing oral cavity squamous cell carcinoma, recurrent disease or second primary tumor (blood samples, buccal biopsies, buccal cells)
measure: alcohol quit
time frame: Month 6, Month 12, Month 24, Month 36, Month 48, Month 60 from inclusion
description: Evaluation of alcohol quit rates for addicted patients (cohorts A and C only)
measure: smoking quit
time frame: Month 6, Month 12, Month 24, Month 36, Month 48, Month 60 from inclusion
description: Evaluation of smoking quit rates for addicted patients (cohorts A and C only)
measure: cannabis quit
time frame: Month 6, Month 12, Month 24, Month 36, Month 48, Month 60 from inclusion
description: Evaluation of cannabis quit rates for addicted patients (cohorts A and C only)
measure: Preclinical models of oral mucosa
time frame: Month 6, Month 12, Month 24, Month 36, Month 48, Month 60 from inclusion
description: Patient-derived preclinical models of oral normal mucosa from smokers/drinkers and non smokers/non drinkers
measure: Preclinical models of OPML
time frame: Month 6, Month 12, Month 24, Month 36, Month 48, Month 60 from inclusion
description: Patient-derived preclinical models of OPML from smokers/drinkers and non smokers/non drinkers
measure: Preclinical models of HNSCC
time frame: Month 6, Month 12, Month 24, Month 36, Month 48, Month 60 from inclusion
description: Patient-derived preclinical models of HNSCC from smokers/drinkers and non smokers/non drinkers
measure: Efficacy of intensive and sustained smoking cessation program
time frame: Month 6, Month 12 after randomization
description: Evaluation of the efficacy of an experimental, intensive and sustained smoking cessation program, versus minimal tobacco cessation intervention, in helping patients with HNSCC to achieve long-term abstinence (at 12 months after randomization), middle term-abstinence (at least 6 months after randomisation) or to reduce cigarette consumption by at least 50% of baseline levels (cohort B only)
measure: Time to smoking resumption
time frame: Month 6, Month 12, Month 24, Month 36, Month 48, Month 60 after randomization
description: Evaluation of the time to smoking resumption (i;e; delay between randomization and smoking resumption) for the patients unable to achieve abstinence in the 2 arms (cohort B only)
measure: Health-related quality of life
time frame: Month 6, Month 12 after randomization
description: Evaluation of the health-related quality of life using quality of life questionnaire QLQ-C30 assessment (cohort B only)
measure: Health-related quality of life
time frame: Month 6, Month 12 after randomization
description: Evaluation of the health-related quality of life using quality of life questionnaire QLQ-H&N35 assessment (cohort B only)
measure: Patients' preference to the 2 smoking cessation programs
time frame: Month 12 after randomization
description: Evaluation of the patients' preference by assessement of the rate of patients who refuse the intensive and sustained smoking cessation program.
measure: Cost of the cessation program
time frame: Month 12 (M12) after randomization
description: Cost of the cessation programs (Cohort B only): addictologist visits, nicotine replacement therapy, behaviorial and cognitive thérapies, psychological interventions...
measure: Correlation between LOH status and smoking cessation
time frame: Month 6 and month 12 (M6, M12) after randomization
description: - To analyze the LOH status at baseline (normal mucosa on resected specimen and tumor) and the dynamics of LOH changes in oral brushes (baseline, M6 and M12) to evaluate whether they may serve as a surrogate of smoking cessation (Cohort B only)
measure: Prevalence of a panel of constitutional genomic variants in genes known to be associated with nicotine dependance
time frame: Day 0 (at randomization)
description: Prevalence of a panel of constitutional genomic variants in genes known to be associated with nicotine dependance in patients refusing assistance for smoking cessation in comparison with patients willing to quit (Cohort B only)
measure: Psychological evaluation
time frame: Within 2 months after randomization
description: to determine psychological characteristics of patients, with a focus on patients who refuse assistance for smoking cessation in comparison with patients willing to quit, to decipher reasons for acceptance or refusal to enter an intensive smoking cessation program and to identify patients representations for their smoking/alcohol addiction and how patients understand their level of risk and cope/react with it (Cohort B only)
measure: Sociological evaluation
time frame: After randomization and Month 6 after randomization
description: to determine sociological characteristics of patients, with a focus on patients who refuse assistance for smoking cessation in comparison with patients willing to quit, to decipher reasons for acceptance or refusal to enter an intensive smoking cessation program and to identify patients representations for their smoking/alcohol addiction and how patients understand their level of risk and cope/react with it (Cohort B only)
arm group label: Cohort A
arm group type: Experimental
description: Samples collection and Tobacco and alcohol status follow-up for patient with OPML:
Follow-up of the lesions (pictures, biopsies, brushes), malignant transformation oversight, smoking and alcohol status follow-up (questionnaires), blood and saliva samples
arm group label: Cohort B
arm group type: Experimental
description: Samples collection; Psychological and Sociological evaluation; Intensive and sustained smoking cessation program; Tobacco and alcohol status follow-up for patient with resectable HNSCC requiring postoperative radiotherapy or chemoradiation and which are either current smokers motivated to quit or reformed smokers within 3 months before the diagnosis of a resectable HNSCC.
Randomization 1:1, arm 1 = minimal tobacco cessation intervention, arm 2 = intensive and sustained smoking cessation program.
Smoking and alcohol status follow-up, adhesion to the smoking cessation program, tumoral follow-up, second malignant lesion, tumoral collection, blood biomarkers research
arm group label: Cohort C
arm group type: Experimental
description: Samples collection and Tobacco and alcohol status follow-up for patients with resectable HNSCC wich are not eligible to cohort B Smoking and alcohol status follow-up (questionnaires), tumoral follow-up, second malignant lesion and OPML lesion appearance oversight, tumoral collection, blood biomarkers research
intervention type: Procedure
intervention name: Samples collection
description: OPML biopsy or resection, biopsy of normal oral mucosa, surgical specimen of HNSCC, saliva samples, buccal brushes, blood samples
arm group label: Cohort A
arm group label: Cohort B
arm group label: Cohort C
intervention type: Behavioral
intervention name: Psychological and Sociological evaluation
description: Cohort B ....
arm group label: Cohort B
intervention type: Behavioral
intervention name: Intensive and sustained smoking cessation program
description: Evaluation of efficacy of the smoking cessation program (intensive and sustained versus minimal)
arm group label: Cohort B
intervention type: Behavioral
intervention name: Tobacco and alcohol status follow-up
description: Evaluation of the tobacco and alcohol status all along the study (questionnaires)
arm group label: Cohort A
arm group label: Cohort B
arm group label: Cohort C
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Pierre SAINTIGNY, Dr
role: Principal Investigator
affiliation: Centre Léon Bérard, Lyon, France
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country: France
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Precancerous Conditions