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/NCT06015035</url>
    </required_header>
    <id_info>
      <org_study_id>k202204-02</org_study_id>
      <nct_id>NCT06015035</nct_id>
    </id_info>
    <brief_title>Sintilimab and Anlotinib Combined With Chemotherapy in Neoadjuvant Treatment of Resectable Esophageal Cancer</brief_title>
    <official_title>A Prospective Single-center, Single-arm, Open-label Study of Sintilimab and Anlotinib Combined With Chemotherapy in Neoadjuvant Treatment of Resectable Esophageal Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Tang-Du Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Tang-Du Hospital</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>
        The study focused on patients with T2-4NxM0 resectable esophageal carcinoma. Neoadjuvant&#xD;
        treatment involved administering anlotinib (10 mg orally, once a day, 2 weeks on and 1 week&#xD;
        off) for anti-angiogenesis and sintilimab (200 mg) and chemotherapyfor three cycles. Surgical&#xD;
        treatment was performed 4-6 weeks after the last chemotherapy cycle was completed. The&#xD;
        primary endpoints assessed were pathological complete response (pCR) rate and safety.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The study was conducted from April 2021 to April 2022 at our hospital and was approved by the&#xD;
        Ethics Committee of Tangdu Hospital. The inclusion criteria were as follows: patients aged&#xD;
        18-75 years with a histopathologic diagnosis of esophageal cancer staged according to the&#xD;
        AJCC eighth edition as T1-4N1-3M0. If patients were staged as T2N0M0, the esophageal lesions&#xD;
        had to be ≥5 cm. Before enrollment, all patients underwent various examinations, including&#xD;
        cardiac color ultrasound (left ventricular ejection fraction of at least 50%), pulmonary&#xD;
        function (forced expiratory volume-1 [FEV1] ≥1.5 L), enhanced chest computed tomography (CT),&#xD;
        abdominal color ultrasound, cervical lymph node color ultrasound and other necessary&#xD;
        laboratory tests (such as blood routine, liver and kidney function, electrolytes, and&#xD;
        cortisol rhythm) to exclude treatment and surgical contraindications and ensure suitability&#xD;
        for ICIs treatment.&#xD;
  &#xD;
        The exclusion criteria were as follows: Patients unable to tolerate surgery, those with&#xD;
        refractory hypertension and proteinuria, those who had previously received other treatments,&#xD;
        and those who were not suitable candidates for ICIs (due to conditions such as hepatitis B&#xD;
        with viral quantification &gt;2000 IU, systemic lupus erythematosus, and xerosis).&#xD;
  &#xD;
        Treatment regimen:&#xD;
  &#xD;
        Patients were administered preoperatively with sintilimab (200 mg, Day 1) and anlotinib (10&#xD;
        mg, orally, once daily, 2 weeks on and 1 week off) in combination with chemotherapy (albumin&#xD;
        paclitaxel 130 mg/m2, Days 1 and 8 + nedaplatin 80 mg/m2, Day 1) for three cycles of&#xD;
        neoadjuvant therapy. Surgical intervention (either Mckeown or Ivor Lewis approach) was&#xD;
        performed 4-6 weeks after completing the last treatment cycle of neoadjuvant therapy. After&#xD;
        the 4th week after surgery, patients received maintenance therapy with sintilimab (200 mg,&#xD;
        Q3W) for 1 year. If any adverse reactions of grade 3 or higher occurred during the treatment,&#xD;
        the dose of chemotherapeutic drugs was reduced by 25% until the patient's condition recovered&#xD;
        to grade 1 or returned to normal, and the subsequent treatment cycle was continued. In case&#xD;
        of grade 3 or higher hypertension or proteinuria, the dose of anlotinib was reduced to 8 mg.&#xD;
        It was discontinued if the condition could not recover to grade 1-2 after symptomatic&#xD;
        treatment.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">April 1, 2021</start_date>
    <completion_date type="Actual">April 1, 2022</completion_date>
    <primary_completion_date type="Actual">April 1, 2022</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Primary Endpoints: pCR</measure>
      <time_frame>up to 24 months</time_frame>
      <description>PCR: This was assessed by examining the postoperative pathological tissue for the absence of tumor cells in the primary tumor and lymph nodes.</description>
    </primary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Actual">17</enrollment>
    <condition>Sintilimab and Anlotinib in Combination With Chemotherapy</condition>
    <arm_group>
      <arm_group_label>anlotinib for anti-angiogenesis and sintilimab and chemotherapy</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Neoadjuvant treatment involved administering anlotinib (10 mg orally, once a day, 2 weeks on and 1 week off) for anti-angiogenesis and sintilimab (200 mg) and chemotherapyfor three cycles.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Sintilimab and anlotinib in combination with chemotherapy</intervention_name>
      <description>Neoadjuvant treatment involved administering anlotinib (10 mg orally, once a day, 2 weeks on and 1 week off) for anti-angiogenesis and sintilimab (200 mg) and chemotherapyfor three cycles. Surgical treatment was performed 4-6 weeks after the last chemotherapy cycle was completed. The primary endpoints assessed were pathological complete response (pCR) rate and safety.</description>
      <arm_group_label>anlotinib for anti-angiogenesis and sintilimab and chemotherapy</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria&#xD;
  &#xD;
            -  patients aged 18-75 years with a histopathologic diagnosis of esophageal cancer staged&#xD;
               according to the AJCC eighth edition as T1-4N1-3M0. If patients were staged as T2N0M0,&#xD;
               the esophageal lesions had to be ≥5 cm.&#xD;
  &#xD;
            -  Before enrollment, all patients underwent various examinations, including cardiac&#xD;
               color ultrasound (left ventricular ejection fraction of at least 50%), pulmonary&#xD;
               function (forced expiratory volume-1 [FEV1] ≥1.5 L), enhanced chest computed&#xD;
               tomography (CT), abdominal color ultrasound, cervical lymph node color ultrasound ▪&#xD;
               other necessary laboratory tests (such as blood routine, liver and kidney function,&#xD;
               electrolytes, and cortisol rhythm) to exclude treatment and surgical ontraindications&#xD;
               and ensure suitability for ICIs treatment.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients unable to tolerate surgery&#xD;
  &#xD;
            -  those with refractory hypertension and proteinuria&#xD;
  &#xD;
            -  those who had previously received other treatments&#xD;
  &#xD;
            -  those who were not suitable candidates for ICIs (due to conditions such as hepatitis B&#xD;
               with viral quantification &gt;2000 IU, systemic lupus erythematosus, and xerosis).&#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>Hongtao Duan</name>
        <address>
          <city>Xi'an</city>
          <state>Shanxi</state>
          <zip>710038</zip>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Tangdu Hospital, the Air Force Military University</name>
        <address>
          <city>Xi'an</city>
          <zip>710038</zip>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 17, 2023</study_first_submitted>
    <study_first_submitted_qc>August 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 29, 2023</study_first_posted>
    <last_update_submitted>August 27, 2023</last_update_submitted>
    <last_update_submitted_qc>August 27, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 29, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Tang-Du Hospital</investigator_affiliation>
      <investigator_full_name>Xiaolong Yan, Dr.</investigator_full_name>
      <investigator_title>Deputy director</investigator_title>
    </responsible_party>
    <keyword>esophageal cancer; neoadjuvant; efficiency</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Esophageal Neoplasms</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
      <ipd_description>If the clinical study obtains positive results, it will further expand the study</ipd_description>
    </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/NCT06015035
  org study id: k202204-02
  nct id: NCT06015035
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The study focused on patients with T2-4NxM0 resectable esophageal carcinoma. Neoadjuvant
        treatment involved administering anlotinib (10 mg orally, once a day, 2 weeks on and 1 week
        off) for anti-angiogenesis and sintilimab (200 mg) and chemotherapyfor three cycles. Surgical
        treatment was performed 4-6 weeks after the last chemotherapy cycle was completed. The
        primary endpoints assessed were pathological complete response (pCR) rate and safety.
  The study was conducted from April 2021 to April 2022 at our hospital and was approved by the
        Ethics Committee of Tangdu Hospital. The inclusion criteria were as follows: patients aged
        18-75 years with a histopathologic diagnosis of esophageal cancer staged according to the
        AJCC eighth edition as T1-4N1-3M0. If patients were staged as T2N0M0, the esophageal lesions
        had to be ≥5 cm. Before enrollment, all patients underwent various examinations, including
        cardiac color ultrasound (left ventricular ejection fraction of at least 50%), pulmonary
        function (forced expiratory volume-1 [FEV1] ≥1.5 L), enhanced chest computed tomography (CT),
        abdominal color ultrasound, cervical lymph node color ultrasound and other necessary
        laboratory tests (such as blood routine, liver and kidney function, electrolytes, and
        cortisol rhythm) to exclude treatment and surgical contraindications and ensure suitability
        for ICIs treatment.
  
        The exclusion criteria were as follows: Patients unable to tolerate surgery, those with
        refractory hypertension and proteinuria, those who had previously received other treatments,
        and those who were not suitable candidates for ICIs (due to conditions such as hepatitis B
        with viral quantification >2000 IU, systemic lupus erythematosus, and xerosis).
  
        Treatment regimen:
  
        Patients were administered preoperatively with sintilimab (200 mg, Day 1) and anlotinib (10
        mg, orally, once daily, 2 weeks on and 1 week off) in combination with chemotherapy (albumin
        paclitaxel 130 mg/m2, Days 1 and 8 + nedaplatin 80 mg/m2, Day 1) for three cycles of
        neoadjuvant therapy. Surgical intervention (either Mckeown or Ivor Lewis approach) was
        performed 4-6 weeks after completing the last treatment cycle of neoadjuvant therapy. After
        the 4th week after surgery, patients received maintenance therapy with sintilimab (200 mg,
        Q3W) for 1 year. If any adverse reactions of grade 3 or higher occurred during the treatment,
        the dose of chemotherapeutic drugs was reduced by 25% until the patient's condition recovered
        to grade 1 or returned to normal, and the subsequent treatment cycle was continued. In case
        of grade 3 or higher hypertension or proteinuria, the dose of anlotinib was reduced to 8 mg.
        It was discontinued if the condition could not recover to grade 1-2 after symptomatic
        treatment.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Primary Endpoints: pCR
  time frame: up to 24 months
  description: PCR: This was assessed by examining the postoperative pathological tissue for the absence of tumor cells in the primary tumor and lymph nodes.
  arm group label: anlotinib for anti-angiogenesis and sintilimab and chemotherapy
  arm group type: Experimental
  description: Neoadjuvant treatment involved administering anlotinib (10 mg orally, once a day, 2 weeks on and 1 week off) for anti-angiogenesis and sintilimab (200 mg) and chemotherapyfor three cycles.
  intervention type: Drug
  intervention name: Sintilimab and anlotinib in combination with chemotherapy
  description: Neoadjuvant treatment involved administering anlotinib (10 mg orally, once a day, 2 weeks on and 1 week off) for anti-angiogenesis and sintilimab (200 mg) and chemotherapyfor three cycles. Surgical treatment was performed 4-6 weeks after the last chemotherapy cycle was completed. The primary endpoints assessed were pathological complete response (pCR) rate and safety.
  arm group label: anlotinib for anti-angiogenesis and sintilimab and chemotherapy
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  facility: 
  facility: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Tang-Du Hospital
  investigator full name: Xiaolong Yan, Dr.
  investigator title: Deputy director
  mesh term: Esophageal Neoplasms
  sharing ipd: Undecided
  ipd description: If the clinical study obtains positive results, it will further expand the study