xml: <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/NCT06039631</url>
    </required_header>
    <id_info>
      <org_study_id>Larynx-IO 2.0</org_study_id>
      <nct_id>NCT06039631</nct_id>
    </id_info>
    <brief_title>Neoadjuvant Chemoimmunotherapy Followed By Radiation Or Organ Preservation Surgery In Laryngeal/Hypopharyngeal Cancer</brief_title>
    <official_title>Neoadjuvant Immunotherapy And Chemotherapy Followed By Concurrent Chemoradiation Or Organ Preservation Surgery In Locally Advanced Laryngeal Cancer And Hypopharyngeal Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Fudan University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Fudan University Eye Ear Nose and Throat Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Shanghai Zhongshan Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Ruijin Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Xinhua Hospital, Shanghai Jiao Tong University School of Medicine</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Fudan University</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <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>
        In the global landscape of cancer, head and neck malignancies are highly prevalent, with&#xD;
        878,000 new cases and 444,000 deaths recorded in 2020. Notably, laryngeal and hypopharyngeal&#xD;
        cancers contribute to around 30% of these instances. More than 50% of patients are diagnosed&#xD;
        with locally advanced disease, necessitating intensive treatments that significantly impact&#xD;
        their quality of life. Despite these efforts, the prognosis for laryngeal and hypopharyngeal&#xD;
        cancers remains grim, with a 5-year survival rate of 30% to 50%.&#xD;
  &#xD;
        Past approaches focused on preserving laryngeal function and patient well-being, including&#xD;
        minimally invasive surgery, advanced radiotherapy, and induction chemotherapy. Our prior&#xD;
        research highlighted the effectiveness of combining toripalimab-based induction therapy and&#xD;
        chemotherapy, followed by concurrent chemoradiotherapy or surgery. Positive short-term&#xD;
        outcomes and manageable side effects were observed, with encouraging larynx preservation&#xD;
        rates after one year.&#xD;
  &#xD;
        Against this backdrop, the current study aims to explore neoadjuvant immunotherapy combined&#xD;
        with chemotherapy for patients with locally advanced laryngeal and hypopharyngeal cancer. It&#xD;
        seeks to compare the therapeutic efficacy and quality of life impacts of concurrent&#xD;
        radiochemotherapy and organ-preserving surgery. The ultimate goal is to identify optimal&#xD;
        strategies for future interventions.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Head and neck cancer stands as one of the most prevalent forms of malignancy on a global&#xD;
        scale. Among these, head and neck squamous cell carcinoma (HNSCC) takes precedence as the&#xD;
        predominant histological subtype, encompassing around 90% of the total caseload. Notably,&#xD;
        laryngeal and hypopharyngeal cancer contribute to approximately 30% of these instances. Upon&#xD;
        initial diagnosis, a striking majority-over 50% of patients find themselves grappling with&#xD;
        locally advanced disease, necessitating an assertive therapeutic approach that significantly&#xD;
        impacts their overall quality of life. Despite the rigor of these treatments, the prognosis&#xD;
        for laryngeal and hypopharyngeal cancer remains discouraging, characterized by a 5-year&#xD;
        overall survival rate ranging between 30% and 50%.&#xD;
  &#xD;
        Past endeavors have been dedicated to preserving laryngeal function and enhancing the&#xD;
        well-being of patients, spanning from the adoption of minimally invasive and organ-conserving&#xD;
        surgical techniques to advancements in radiotherapy and the advent of induction chemotherapy.&#xD;
        Recent strides in immunotherapy, particularly the integration of programmed cell death&#xD;
        protein-1 (PD-1) inhibitors, have brought about a remarkable paradigm shift in how&#xD;
        recurrent/metastatic HNSCC is managed. Our previous investigation underscored the efficacy of&#xD;
        the strategy involving the combination of toripalimab-based induction therapy and&#xD;
        chemotherapy, followed by concurrent chemoradiotherapy or surgical intervention, showcasing&#xD;
        favorable short-term outcomes and manageable adverse effects. The data further revealed&#xD;
        highly promising larynx preservation rates at the one-year mark.&#xD;
  &#xD;
        Given this backdrop, the present study seeks to delve into patients experiencing partial&#xD;
        relief through neoadjuvant immunotherapy combined with chemotherapy in cases of locally&#xD;
        advanced laryngeal and hypopharyngeal cancer. The study aims to compare the therapeutic&#xD;
        efficacy and discrepancies in quality of life resulting from concurrent radiochemotherapy and&#xD;
        organ-preserving surgical treatment. The overarching goal is to delineate optimal strategies&#xD;
        for subsequent interventions.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 22, 2023</start_date>
    <completion_date type="Anticipated">September 1, 2029</completion_date>
    <primary_completion_date type="Anticipated">September 1, 2027</primary_completion_date>
    <phase>Phase 2</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>
      <intervention_model_description>the selection trial design</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Progression-free survival rate</measure>
      <time_frame>At two year post-randomization</time_frame>
      <description>Progression-free survival is defined as the time interval from the commencement of randomization until the first documented occurrence of objective tumor progression or death due to any cause, whichever comes first.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Larynx Preservation rate</measure>
      <time_frame>At two year post-randomization</time_frame>
      <description>Larynx-preservation is considered to have failed on the date of total laryngectomy, or evidence of local recurrence on primary site.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival rate</measure>
      <time_frame>At two year post-randomization</time_frame>
      <description>Overall survival is measured as the time from the initiation of randomization to the occurrence of death due to any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Quality of life</measure>
      <time_frame>From enrollment to two year post-randomization</time_frame>
      <description>Evaluated by MD Anderson Dysphagia Inventory, Voice Handicap Index 10</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse events</measure>
      <time_frame>From enrollment to two year post-randomization</time_frame>
      <description>Adverse events evaluated by CTCAE 5.0 criteria</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">82</enrollment>
    <condition>Larynx Cancer</condition>
    <condition>Hypopharyngeal Cancer</condition>
    <arm_group>
      <arm_group_label>Organ preservation surgery</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>In the surgical group, patients will undergo curative surgery for laryngeal/hypopharyngeal cancer along with cervical lymph node dissection. Organ preservation surgery is recommended, and the specific surgical approach will be chosen based on individual case characteristics and the treatment protocols followed at our center. Depending on postoperative pathology results, adjuvant radiotherapy or concurrent radiochemotherapy may be administered as deemed necessary. If postoperative pathology indicates extracapsular invasion of lymph nodes or positive surgical margins, concurrent radiochemotherapy based on cisplatin is recommended. Starting three weeks after the completion of radiotherapy, patients will receive adjuvant immunotherapy using a specific protocol of toripalimab at a dose of 240 mg every 3 weeks for a total of 8 cycles.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Concurrent chemoradiation</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>In the concurrent radiochemotherapy group, patients will undergo target delineation based on the scope before induction chemotherapy. Radiotherapy will be administered at a total dose of 70 Gy over 35 fractions, and concurrent chemotherapy will involve weekly administration of cisplatin. Starting three weeks after the completion of radiotherapy, patients will receive adjuvant immunotherapy using a specific protocol of toripalimab at a dose of 240 mg every 3 weeks for a total of 8 cycles.</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Surgery</intervention_name>
      <description>In the surgical group, patients will undergo curative surgery for laryngeal/hypopharyngeal cancer along with cervical lymph node dissection. Organ preservation surgery is recommended.</description>
      <arm_group_label>Organ preservation surgery</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>Radiation</intervention_name>
      <description>In the surgical group, depending on postoperative pathology results, adjuvant radiotherapy or concurrent radiochemotherapy may be administered as deemed necessary. If postoperative pathology indicates extracapsular invasion of lymph nodes or positive surgical margins, concurrent radiochemotherapy based on cisplatin is recommended.&#xD;
  In the concurrent radiochemotherapy group, patients will undergo target delineation based on the scope before induction chemotherapy. Radiotherapy will be administered at a total dose of 70 Gy over 35 fractions, and concurrent chemotherapy will involve weekly administration of cisplatin at a dosage of 30 mg/m².</description>
      <arm_group_label>Concurrent chemoradiation</arm_group_label>
      <arm_group_label>Organ preservation surgery</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Toripalimab</intervention_name>
      <description>In the both groups, starting three weeks after the completion of radiotherapy, patients will receive adjuvant immunotherapy using a specific protocol of toripalimab at a dose of 240 mg every 3 weeks for a total of 8 cycles.</description>
      <arm_group_label>Concurrent chemoradiation</arm_group_label>
      <arm_group_label>Organ preservation surgery</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Signing of the informed consent form and willingness to comply with the study&#xD;
               protocol.&#xD;
  &#xD;
            2. Age ≥18 and ≤75 years.&#xD;
  &#xD;
            3. Histologically confirmed laryngeal or hypopharyngeal squamous cell carcinoma.&#xD;
  &#xD;
            4. Locally advanced laryngeal/hypopharyngeal cancer patients eligible for surgical&#xD;
               resection (AJCC 8th edition stage: T2N+M0, T3-T4aN0-3M0).&#xD;
  &#xD;
            5. Presence of at least one measurable lesion before treatment, in accordance with RECIST&#xD;
               1.1 criteria for &quot;measurable lesions.&quot;&#xD;
  &#xD;
            6. Patients who have received neoadjuvant immunotherapy combined with chemotherapy and&#xD;
               have achieved a partial response (PR) in the primary lesion according to RECIST 1.1&#xD;
               criteria and are suitable candidates for organ preservation surgery.&#xD;
  &#xD;
            7. Expected survival of more than 3 months.&#xD;
  &#xD;
            8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.&#xD;
  &#xD;
            9. Good organ function, meeting the following criteria:&#xD;
  &#xD;
                 1. Absolute neutrophil count (ANC) ≥1.5×10^9/L.&#xD;
  &#xD;
                 2. Platelet count ≥100×10^9/L.&#xD;
  &#xD;
                 3. Hemoglobin ≥9 g/dL.&#xD;
  &#xD;
                 4. Serum albumin ≥2.8 g/dL.&#xD;
  &#xD;
                 5. Total bilirubin ≤1.5× upper limit of normal (ULN), ALT, AST, and/or ALP ≤3× ULN.&#xD;
  &#xD;
                 6. Serum creatinine ≤1.5× ULN and creatinine clearance ≥60 mL/min (Cockcroft-Gault&#xD;
                    formula, see Appendix III).&#xD;
  &#xD;
                 7. Activated partial thromboplastin time (APTT) and international normalized ratio&#xD;
                    (INR) ≤1.5× ULN (patients on stable doses of anticoagulation with agents like low&#xD;
                    molecular weight heparin or warfarin, and INR within the expected therapeutic&#xD;
                    range, may be included).&#xD;
  &#xD;
           10. Patients with hepatitis B virus (HBV) infection, inactive/asymptomatic HBV carriers,&#xD;
               or patients with chronic or active HBV infection with HBV DNA &lt;500 IU/mL (or 2500&#xD;
               copies/mL) at screening will be allowed to participate. Patients positive for&#xD;
               hepatitis C antibodies, if HCV-RNA is negative at screening, will be allowed to&#xD;
               participate.&#xD;
  &#xD;
           11. Females of childbearing potential must have a negative pregnancy test result in urine&#xD;
               or serum ≤7 days before treatment initiation. They must use a medically accepted&#xD;
               contraceptive measure (such as intrauterine device, oral contraceptives, or condoms)&#xD;
               during the study treatment period, for at least 3 months after the last dose of&#xD;
               toripalimab, and for at least 6 months after the last dose of chemotherapy.&#xD;
  &#xD;
           12. Non-sterilized male participants must be willing to use a medically accepted&#xD;
               contraceptive measure (such as intrauterine device, oral contraceptives, or condoms)&#xD;
               during the study treatment period, for at least 3 months after the last dose of&#xD;
               toripalimab, and for at least 6 months after the last dose of chemotherapy.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. History of allergic reactions to any components of toripalimab, paclitaxel, or&#xD;
               cisplatin.&#xD;
  &#xD;
            2. Pre-existing tracheostomy due to laryngeal dysfunction before treatment.&#xD;
  &#xD;
            3. History of or concurrent presence of other malignancies (except for those cured and&#xD;
               with no cancer-related survival exceeding 5 years, such as basal cell carcinoma of the&#xD;
               skin, cervical carcinoma in situ, and papillary thyroid cancer). Patients with&#xD;
               concurrent hypopharyngeal and esophageal cancers, where the lesions are not&#xD;
               anatomically adjacent, will be diagnosed as having dual primary tumors and will not be&#xD;
               eligible for inclusion.&#xD;
  &#xD;
            4. Uncontrolled clinical cardiac symptoms or diseases, including:&#xD;
  &#xD;
                 1. NYHA Class II or higher heart failure.&#xD;
  &#xD;
                 2. Unstable angina.&#xD;
  &#xD;
                 3. Myocardial infarction within the past year.&#xD;
  &#xD;
                 4. Clinically significant ventricular or supraventricular arrhythmias requiring&#xD;
                    clinical intervention.&#xD;
  &#xD;
            5. Previous treatment with any of the following:&#xD;
  &#xD;
                 1. Use of any investigational drug within 4 weeks prior to the first dose of study&#xD;
                    treatment.&#xD;
  &#xD;
                 2. Concurrent participation in another clinical trial, unless it is an observational&#xD;
                    (non-interventional) clinical trial.&#xD;
  &#xD;
                 3. Requiring systemic treatment with corticosteroids (daily dose &gt;10 mg prednisone&#xD;
                    equivalent) or other immunosuppressive medications within 2 weeks prior to the&#xD;
                    first dose of study treatment, excluding corticosteroids for localized&#xD;
                    inflammation or prophylaxis against allergies or nausea/vomiting. Other specific&#xD;
                    circumstances should be discussed with the investigator. In the absence of active&#xD;
                    autoimmune disease, inhaled or topical steroids and adrenal replacement therapy&#xD;
                    with a dose of &gt;10 mg/day prednisone or equivalent are allowed.&#xD;
  &#xD;
                 4. Vaccination with anti-tumor vaccines or administration of live vaccines within 4&#xD;
                    weeks prior to the first dose of study treatment (for patients who received&#xD;
                    COVID-19 vaccine, a 2-week interval is required).&#xD;
  &#xD;
                 5. Major surgery within 4 weeks before the first dose of study treatment or presence&#xD;
                    of severe trauma.&#xD;
  &#xD;
            6. Failure to recover to ≤ Grade 1 toxicity per CTCAE (except for alopecia and residual&#xD;
               neuropathy related to prior platinum therapy) from previous cancer therapy or from any&#xD;
               other cause unrelated to study/enrollment criteria.&#xD;
  &#xD;
            7. Experience of severe infections (CTCAE &gt; Grade 2) within 4 weeks before the first dose&#xD;
               of study treatment, such as severe pneumonia requiring hospitalization, sepsis, or&#xD;
               complicated infections. Baseline chest imaging indicating active pulmonary&#xD;
               inflammation, presence of symptoms and signs of infection within 4 weeks before the&#xD;
               first dose of study treatment, or requirement for oral or intravenous antibiotics to&#xD;
               treat infection are exclusion criteria.&#xD;
  &#xD;
            8. Active autoimmune disease or history of autoimmune disease, such as interstitial lung&#xD;
               disease, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism,&#xD;
               hypothyroidism, including but not limited to these diseases or syndromes. However,&#xD;
               stable dose of thyroid replacement therapy for autoimmune-mediated hypothyroidism is&#xD;
               allowed. Stable dose of insulin for type I diabetes is allowed. Patients with vitiligo&#xD;
               or childhood-onset asthma/allergies requiring no intervention as adults are allowed.&#xD;
  &#xD;
            9. History of immune deficiency, including HIV positive test results, other acquired or&#xD;
               congenital immunodeficiency diseases, or history of organ transplantation or&#xD;
               allogeneic bone marrow transplantation.&#xD;
  &#xD;
           10. History of interstitial lung disease (excluding radiation pneumonitis not treated with&#xD;
               steroids), non-infectious pneumonitis.&#xD;
  &#xD;
           11. Active tuberculosis infection found through medical history or CT scan, or presence of&#xD;
               active tuberculosis infection within the past year prior to enrollment, or history of&#xD;
               active tuberculosis infection more than 1 year ago but not formally treated.&#xD;
  &#xD;
           12. Presence of active hepatitis B (HBV DNA ≥500 IU/mL or 2500 copies/mL) or hepatitis C&#xD;
               (HCV-RNA positive with HCV-RNA levels above the lower limit of detection of the assay)&#xD;
               infection＊.&#xD;
  &#xD;
           13. Known history of substance abuse, alcohol abuse, or drug addiction.&#xD;
  &#xD;
           14. Pregnant or breastfeeding women.&#xD;
  &#xD;
           15. Other factors, as judged by the investigator, that may interfere with the&#xD;
               participant's ability to comply with the study requirements or that may jeopardize the&#xD;
               safety of the participant or the quality of the study data, including the presence of&#xD;
               other severe diseases (including mental illness) requiring concurrent treatment,&#xD;
               severe abnormal laboratory values, family or social factors, which might affect&#xD;
               participant safety or data collection.&#xD;
  &#xD;
                 -  For participants who are HBsAg-positive and either HBV DNA-negative or with HBV&#xD;
                    DNA &lt;500 IU/mL or 2500 copies/mL, after receiving stable antiviral treatment,&#xD;
                    they may be included in this trial (treatment should be ongoing for &gt;2 weeks&#xD;
                    before enrollment, and continued for 6 months after the last dose of study&#xD;
                    treatment).&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>Fudan University Shanghai Cancer Center</name>
        <address>
          <city>Shanghai</city>
          <state>Shanghai</state>
          <zip>200032</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Yu Wang, M.D.</last_name>
        <phone>+8618017313971</phone>
        <email>neck130@hotmail.com</email>
      </contact>
      <contact_backup>
        <last_name>Xiaomin Ou, M.D.</last_name>
        <phone>+8618017317872</phone>
        <email>0456218@fudan.edu.cn</email>
      </contact_backup>
      <investigator>
        <last_name>Yu Wang</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 9, 2023</study_first_submitted>
    <study_first_submitted_qc>September 9, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 15, 2023</study_first_posted>
    <last_update_submitted>September 9, 2023</last_update_submitted>
    <last_update_submitted_qc>September 9, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Fudan University</investigator_affiliation>
      <investigator_full_name>Yu Wang</investigator_full_name>
      <investigator_title>M.D., Chair</investigator_title>
    </responsible_party>
    <keyword>organ preservation</keyword>
    <keyword>PD-1 inhibitor</keyword>
    <keyword>Immunotherapy</keyword>
    <keyword>Neoadjuvant chemotherapy</keyword>
    <keyword>Induction chemotherapy</keyword>
    <keyword>larynx presrvation surgery</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Hypopharyngeal Neoplasms</mesh_term>
      <mesh_term>Laryngeal Neoplasms</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>The sharing of inviduual participant data will be decided after the pubilcation of this research and the approvement of IRB of Fudan Univerisity Shanghai Cancer Center</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_time_frame>After the pubilcation of this study and the approvement of IRB, till two years after pubilcation.</ipd_time_frame>
      <ipd_access_criteria>The data will be assessed via contact with principal investigator.</ipd_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06039631
  org study id: Larynx-IO 2.0
  nct id: NCT06039631
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  In the global landscape of cancer, head and neck malignancies are highly prevalent, with
        878,000 new cases and 444,000 deaths recorded in 2020. Notably, laryngeal and hypopharyngeal
        cancers contribute to around 30% of these instances. More than 50% of patients are diagnosed
        with locally advanced disease, necessitating intensive treatments that significantly impact
        their quality of life. Despite these efforts, the prognosis for laryngeal and hypopharyngeal
        cancers remains grim, with a 5-year survival rate of 30% to 50%.
  
        Past approaches focused on preserving laryngeal function and patient well-being, including
        minimally invasive surgery, advanced radiotherapy, and induction chemotherapy. Our prior
        research highlighted the effectiveness of combining toripalimab-based induction therapy and
        chemotherapy, followed by concurrent chemoradiotherapy or surgery. Positive short-term
        outcomes and manageable side effects were observed, with encouraging larynx preservation
        rates after one year.
  
        Against this backdrop, the current study aims to explore neoadjuvant immunotherapy combined
        with chemotherapy for patients with locally advanced laryngeal and hypopharyngeal cancer. It
        seeks to compare the therapeutic efficacy and quality of life impacts of concurrent
        radiochemotherapy and organ-preserving surgery. The ultimate goal is to identify optimal
        strategies for future interventions.
  Head and neck cancer stands as one of the most prevalent forms of malignancy on a global
        scale. Among these, head and neck squamous cell carcinoma (HNSCC) takes precedence as the
        predominant histological subtype, encompassing around 90% of the total caseload. Notably,
        laryngeal and hypopharyngeal cancer contribute to approximately 30% of these instances. Upon
        initial diagnosis, a striking majority-over 50% of patients find themselves grappling with
        locally advanced disease, necessitating an assertive therapeutic approach that significantly
        impacts their overall quality of life. Despite the rigor of these treatments, the prognosis
        for laryngeal and hypopharyngeal cancer remains discouraging, characterized by a 5-year
        overall survival rate ranging between 30% and 50%.
  
        Past endeavors have been dedicated to preserving laryngeal function and enhancing the
        well-being of patients, spanning from the adoption of minimally invasive and organ-conserving
        surgical techniques to advancements in radiotherapy and the advent of induction chemotherapy.
        Recent strides in immunotherapy, particularly the integration of programmed cell death
        protein-1 (PD-1) inhibitors, have brought about a remarkable paradigm shift in how
        recurrent/metastatic HNSCC is managed. Our previous investigation underscored the efficacy of
        the strategy involving the combination of toripalimab-based induction therapy and
        chemotherapy, followed by concurrent chemoradiotherapy or surgical intervention, showcasing
        favorable short-term outcomes and manageable adverse effects. The data further revealed
        highly promising larynx preservation rates at the one-year mark.
  
        Given this backdrop, the present study seeks to delve into patients experiencing partial
        relief through neoadjuvant immunotherapy combined with chemotherapy in cases of locally
        advanced laryngeal and hypopharyngeal cancer. The study aims to compare the therapeutic
        efficacy and discrepancies in quality of life resulting from concurrent radiochemotherapy and
        organ-preserving surgical treatment. The overarching goal is to delineate optimal strategies
        for subsequent interventions.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: the selection trial design
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Progression-free survival rate
  time frame: At two year post-randomization
  description: Progression-free survival is defined as the time interval from the commencement of randomization until the first documented occurrence of objective tumor progression or death due to any cause, whichever comes first.
  measure: Larynx Preservation rate
  time frame: At two year post-randomization
  description: Larynx-preservation is considered to have failed on the date of total laryngectomy, or evidence of local recurrence on primary site.
  measure: Overall Survival rate
  time frame: At two year post-randomization
  description: Overall survival is measured as the time from the initiation of randomization to the occurrence of death due to any cause.
  measure: Quality of life
  time frame: From enrollment to two year post-randomization
  description: Evaluated by MD Anderson Dysphagia Inventory, Voice Handicap Index 10
  measure: Adverse events
  time frame: From enrollment to two year post-randomization
  description: Adverse events evaluated by CTCAE 5.0 criteria
  arm group label: Organ preservation surgery
  arm group type: Experimental
  description: In the surgical group, patients will undergo curative surgery for laryngeal/hypopharyngeal cancer along with cervical lymph node dissection. Organ preservation surgery is recommended, and the specific surgical approach will be chosen based on individual case characteristics and the treatment protocols followed at our center. Depending on postoperative pathology results, adjuvant radiotherapy or concurrent radiochemotherapy may be administered as deemed necessary. If postoperative pathology indicates extracapsular invasion of lymph nodes or positive surgical margins, concurrent radiochemotherapy based on cisplatin is recommended. Starting three weeks after the completion of radiotherapy, patients will receive adjuvant immunotherapy using a specific protocol of toripalimab at a dose of 240 mg every 3 weeks for a total of 8 cycles.
  arm group label: Concurrent chemoradiation
  arm group type: Other
  description: In the concurrent radiochemotherapy group, patients will undergo target delineation based on the scope before induction chemotherapy. Radiotherapy will be administered at a total dose of 70 Gy over 35 fractions, and concurrent chemotherapy will involve weekly administration of cisplatin. Starting three weeks after the completion of radiotherapy, patients will receive adjuvant immunotherapy using a specific protocol of toripalimab at a dose of 240 mg every 3 weeks for a total of 8 cycles.
  intervention type: Procedure
  intervention name: Surgery
  description: In the surgical group, patients will undergo curative surgery for laryngeal/hypopharyngeal cancer along with cervical lymph node dissection. Organ preservation surgery is recommended.
  arm group label: Organ preservation surgery
  intervention type: Radiation
  intervention name: Radiation
  description: In the surgical group, depending on postoperative pathology results, adjuvant radiotherapy or concurrent radiochemotherapy may be administered as deemed necessary. If postoperative pathology indicates extracapsular invasion of lymph nodes or positive surgical margins, concurrent radiochemotherapy based on cisplatin is recommended.
  In the concurrent radiochemotherapy group, patients will undergo target delineation based on the scope before induction chemotherapy. Radiotherapy will be administered at a total dose of 70 Gy over 35 fractions, and concurrent chemotherapy will involve weekly administration of cisplatin at a dosage of 30 mg/m².
  arm group label: Concurrent chemoradiation
  arm group label: Organ preservation surgery
  intervention type: Drug
  intervention name: Toripalimab
  description: In the both groups, starting three weeks after the completion of radiotherapy, patients will receive adjuvant immunotherapy using a specific protocol of toripalimab at a dose of 240 mg every 3 weeks for a total of 8 cycles.
  arm group label: Concurrent chemoradiation
  arm group label: Organ preservation surgery
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Fudan University
  investigator full name: Yu Wang
  investigator title: M.D., Chair
  mesh term: Hypopharyngeal Neoplasms
  mesh term: Laryngeal Neoplasms
  sharing ipd: Yes
  ipd description: The sharing of inviduual participant data will be decided after the pubilcation of this research and the approvement of IRB of Fudan Univerisity Shanghai Cancer Center
  ipd info type: Study Protocol
  ipd time frame: After the pubilcation of this study and the approvement of IRB, till two years after pubilcation.
  ipd access criteria: The data will be assessed via contact with principal investigator.