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/NCT05996484</url>
    </required_header>
    <id_info>
      <org_study_id>NFEC-2023-310</org_study_id>
      <nct_id>NCT05996484</nct_id>
    </id_info>
    <brief_title>Neoadjuvant Therapy of Anlotinib Combined With Toripalimab and Chemotherapy for Resectable Esophageal Carcinoma</brief_title>
    <official_title>Anlotinib in Combination With Toripalimab and Chemotherapy for Neoadjuvant Treatment of Resectable Esophageal Squamous Cell Carcinoma: a Phase II Clinical Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Nanfang Hospital, Southern Medical University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Nanfang Hospital, Southern Medical University</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this study is to explore the effectiveness and safety of the combination of&#xD;
        Anlotinib, Toripalimab, and albumin-bound paclitaxel with cisplatin for neoadjuvant therapy&#xD;
        in resectable esophageal squamous cell carcinoma. The study aims to improve the pathological&#xD;
        complete response rate (pCR), R0 resection rate, and disease-free survival (DFS) in patients&#xD;
        undergoing esophageal cancer surgery. The findings of this study will provide guidance and&#xD;
        new options for the treatment of locally advanced esophageal cancer patients.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Both anti-angiogenic therapy and immune checkpoint inhibitors have shown preliminary efficacy&#xD;
        and safety data in the field of neoadjuvant therapy for esophageal cancer. However, there is&#xD;
        currently no available data on the combination of immune checkpoint inhibitors,&#xD;
        anti-angiogenic therapy, and chemotherapy in neoadjuvant therapy for esophageal cancer. Based&#xD;
        on the favorable survival benefits of this combination in first-line and second-line&#xD;
        treatments for multiple tumors, we aim to explore another neoadjuvant treatment approach -&#xD;
        adding anti-angiogenic agents to immune checkpoint inhibitor-based neoadjuvant therapy,&#xD;
        providing a new perioperative treatment strategy for esophageal cancer.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">July 2026</completion_date>
    <primary_completion_date type="Anticipated">November 2024</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>Pathologic complete remission (PCR)</measure>
      <time_frame>Immediately after the surgery</time_frame>
      <description>Primary tumor or lymph node surgery specimen pathological examination without residual tumor cell</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>R0 resection rate</measure>
      <time_frame>Immediately after the surgery</time_frame>
      <description>Residual tumor rate</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective response rate (ORR)</measure>
      <time_frame>Up to 36 month</time_frame>
      <description>ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease control rate (DCR)</measure>
      <time_frame>Up to 36 month</time_frame>
      <description>DCR is defined as the percentage of participants in the analysis population who have a CR, PR or stable disease (SD) per RECIST 1.1.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease-free survival (DFS)</measure>
      <time_frame>3(5) years after last patient enrolled</time_frame>
      <description>Survival without local or systemic recurrence</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>Up to 36 month</time_frame>
      <description>Overall survival is defined as the duration from date of enrollment to the date of death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety: AE</measure>
      <time_frame>Up to 36 month</time_frame>
      <description>Safety was defined as the Number of Participants With an Adverse Event</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change From Baseline in HRQoL Score Using EORTC Quality of Life Questionnaire-Oesophageal Module (QLQ-OES18)</measure>
      <time_frame>Up to 36 month</time_frame>
      <description>The EORTC QLQ-OES18 is a disease-specific questionnaire to assess measurements specific to esophageal cancer. It contains 18 items and is based on four subscales-dysphagia, eating, reflux and pain. All items are scored using a four-point scale that offers these response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. A higher score indicates worse level of symptoms. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in HRQoL QLQ-OES18 score in participants will be presented.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">25</enrollment>
    <condition>Esophageal Carcinoma</condition>
    <condition>Neoadjuvant Therapy</condition>
    <arm_group>
      <arm_group_label>Neoadjuvant Anlotinib Combined With Toripalimab and Chemotherapy</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Toripalimab+ Anlotinib+Albumin-bound paclitaxel+Cisplatin</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Toripalimab</intervention_name>
      <description>Toripalimab, 240mg, IV., D1, every 3 weeks, 4 cycles.</description>
      <arm_group_label>Neoadjuvant Anlotinib Combined With Toripalimab and Chemotherapy</arm_group_label>
      <other_name>JS001</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Anlotinib hydrochloride</intervention_name>
      <description>Anlotinib Hydrochloride is a capsule in the form of 8 mg ,10 mg and 12 mg, orally, once daily, 2 weeks on/1 week off, every 3 weeks, 4 cycles.</description>
      <arm_group_label>Neoadjuvant Anlotinib Combined With Toripalimab and Chemotherapy</arm_group_label>
      <other_name>Anlotinib</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Albumin paclitaxel</intervention_name>
      <description>Albumin paclitaxel, 200-260 mg/m2, IV., D1, every 3 weeks, 4 cycles.</description>
      <arm_group_label>Neoadjuvant Anlotinib Combined With Toripalimab and Chemotherapy</arm_group_label>
      <other_name>Paclitaxel For Injection (Albumin Bound)</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cisplatin</intervention_name>
      <description>Cisplatin, 60-75 mg/m2, IV., D1, every 3 weeks, 4 cycles.</description>
      <arm_group_label>Neoadjuvant Anlotinib Combined With Toripalimab and Chemotherapy</arm_group_label>
      <other_name>CDDP</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age range: 18-70 years, both male and female.&#xD;
  &#xD;
            2. Patients with histopathological diagnosis of esophageal squamous cell carcinoma&#xD;
               confirmed by gastroscopy/ultrasound gastroscopy, and clinical diagnosis of cT2N1-2M0&#xD;
               or cT3N0-2M0, with TNM staging of stage II-III B.&#xD;
  &#xD;
            3. Non-cervical esophageal cancer patients.&#xD;
  &#xD;
            4. No prior systemic or local treatment for esophageal cancer, with at least one&#xD;
               measurable lesion for imaging evaluation of neoadjuvant therapy according to RECIST&#xD;
               1.1 criteria.&#xD;
  &#xD;
            5. ECOG PS (Eastern Cooperative Oncology Group Performance Status): 0-1.&#xD;
  &#xD;
            6. Estimated survival period ≥12 months.&#xD;
  &#xD;
            7. Subjects without significant dysfunction of major organs, with normal assessment of&#xD;
               thyroid, lung, liver, kidney, and cardiac function.&#xD;
  &#xD;
            8. Reproductive-age women must have taken reliable contraceptive measures or undergone&#xD;
               pregnancy testing (serum or urine) within 7 days prior to enrollment, with negative&#xD;
               results, and be willing to use appropriate contraception during the trial and for 8&#xD;
               weeks after the last administration of the investigational drug. For males, they must&#xD;
               agree to use appropriate contraception during the trial and for 8 weeks after the last&#xD;
               administration of the investigational drug, or have undergone surgical sterilization.&#xD;
  &#xD;
            9. Subjects voluntarily participate in this study, sign an informed consent form,&#xD;
               demonstrate good compliance, adhere to the planned schedule for regular clinical&#xD;
               follow-up and necessary treatment, and cooperate in obtaining regular blood and tissue&#xD;
               samples.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Patients who have had or currently have other malignant tumors within the past 1.5&#xD;
               years, except for cured cervical carcinoma in situ, non-melanoma skin cancer, and&#xD;
               superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ), and T1&#xD;
               (tumor invades lamina propria)].&#xD;
  &#xD;
            2. Patients with ulcerative esophageal squamous cell carcinoma.&#xD;
  &#xD;
            3. Patients with esophageal fistula or tracheal fistula.&#xD;
  &#xD;
            4. Patients allergic to anlotinib, toripalimab, or albumin-bound paclitaxel.&#xD;
  &#xD;
            5. Patients with a history of immunodeficiency diseases, including HIV-positive patients&#xD;
               or those with other acquired or congenital immunodeficiency diseases, or a history of&#xD;
               organ transplantation.&#xD;
  &#xD;
            6. Patients with severe and/or uncontrolled diseases are excluded from the study,&#xD;
               including:&#xD;
  &#xD;
               6.1 Patients with unsatisfactory blood pressure control (systolic blood pressure ≥160&#xD;
               mm Hg or diastolic blood pressure ≥100 mmHg).&#xD;
  &#xD;
               6.2 Patients with grade I or higher myocardial ischemia or myocardial infarction.&#xD;
  &#xD;
               6.3 Patients with arrhythmia (including QT interval ≥480 ms) and grade I heart&#xD;
               failure.&#xD;
  &#xD;
               6.4 Patients with poorly controlled diabetes (fasting blood glucose &gt;10 mmol/L) or&#xD;
               receiving high-dose glucocorticoid therapy.&#xD;
  &#xD;
               6.5 Patients with active or uncontrolled severe infections. 6.6 Patients with&#xD;
               decompensated liver disease, active hepatitis B (HBV-DNA ≥10^4 copies/ml or 2000&#xD;
               IU/ml), or hepatitis C (positive for hepatitis C antibodies and HCV RNA) exceeding the&#xD;
               lower limit of the analytical method.&#xD;
  &#xD;
               6.7 Patients with hyperthyroidism or hypothyroidism. 6.8 Patients with active&#xD;
               tuberculosis.&#xD;
  &#xD;
            7. Unresolved toxicities of grade 2 or higher, excluding alopecia, caused by any prior&#xD;
               treatment.&#xD;
  &#xD;
            8. Individuals with multiple factors that affect oral medication administration, such as&#xD;
               dysphagia, chronic diarrhea, and intestinal obstruction.&#xD;
  &#xD;
            9. Individuals with urine routine showing urinary protein ≥++, and confirmed 24-hour&#xD;
               urine protein quantification &gt;1.0 g.&#xD;
  &#xD;
           10. Individuals who underwent major surgical treatment, incisional biopsy, or significant&#xD;
               traumatic injury within 28 days prior to randomization.&#xD;
  &#xD;
           11. Abnormal coagulation function: INR &gt;1.5 or prothrombin time (PT) &gt; ULN + 4 seconds or&#xD;
               APTT &gt; 1.5 ULN, with a bleeding tendency or receiving thrombolytic or anticoagulation&#xD;
               therapy. Patients who experienced any bleeding or hemorrhagic events ≥ grade 3 CTCAE&#xD;
               within 4 weeks prior to randomization, with unhealed wounds, ulcers, or fractures.&#xD;
  &#xD;
           12. Occurrence of arterial/venous thrombotic events within 6 months, such as&#xD;
               cerebrovascular accidents (including transient ischemic attacks), deep vein&#xD;
               thrombosis, and pulmonary embolism.&#xD;
  &#xD;
           13. Pregnant or lactating women.&#xD;
  &#xD;
           14. Presence of distant metastasis.&#xD;
  &#xD;
           15. Patients with significant bone marrow suppression.&#xD;
  &#xD;
           16. Patients with mental illness or a history of substance abuse with psychotropic drugs.&#xD;
  &#xD;
           17. Patients who participated in other drug clinical trials within 4 weeks.&#xD;
  &#xD;
           18. Patients with accompanying diseases that, in the investigator's judgment, pose a&#xD;
               serious risk to patient safety or may affect the patient's completion of the study.&#xD;
  &#xD;
           19. Patients with inherited bleeding tendencies, coagulation disorders, potential invasion&#xD;
               of major blood vessels, and other bleeding risks, who experienced clinically&#xD;
               significant bleeding symptoms or had a clear bleeding tendency with gastrointestinal&#xD;
               bleeding, bleeding gastric ulcers, baseline fecal occult blood ++ and above within 3&#xD;
               months prior to enrollment.&#xD;
  &#xD;
           20. Patients deemed unsuitable&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>kaican cai, M.D., PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Nanfang Hospital, Southern Medical University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>di lu, M.D., PhD</last_name>
      <phone>13268379321</phone>
      <email>david_lu1989@163.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 10, 2023</study_first_submitted>
    <study_first_submitted_qc>August 10, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 18, 2023</study_first_posted>
    <last_update_submitted>August 16, 2023</last_update_submitted>
    <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carcinoma</mesh_term>
      <mesh_term>Esophageal Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Paclitaxel</mesh_term>
      <mesh_term>Albumin-Bound Paclitaxel</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </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/NCT05996484
  org study id: NFEC-2023-310
  nct id: NCT05996484
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  The purpose of this study is to explore the effectiveness and safety of the combination of
        Anlotinib, Toripalimab, and albumin-bound paclitaxel with cisplatin for neoadjuvant therapy
        in resectable esophageal squamous cell carcinoma. The study aims to improve the pathological
        complete response rate (pCR), R0 resection rate, and disease-free survival (DFS) in patients
        undergoing esophageal cancer surgery. The findings of this study will provide guidance and
        new options for the treatment of locally advanced esophageal cancer patients.
  Both anti-angiogenic therapy and immune checkpoint inhibitors have shown preliminary efficacy
        and safety data in the field of neoadjuvant therapy for esophageal cancer. However, there is
        currently no available data on the combination of immune checkpoint inhibitors,
        anti-angiogenic therapy, and chemotherapy in neoadjuvant therapy for esophageal cancer. Based
        on the favorable survival benefits of this combination in first-line and second-line
        treatments for multiple tumors, we aim to explore another neoadjuvant treatment approach -
        adding anti-angiogenic agents to immune checkpoint inhibitor-based neoadjuvant therapy,
        providing a new perioperative treatment strategy for esophageal cancer.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Pathologic complete remission (PCR)
  time frame: Immediately after the surgery
  description: Primary tumor or lymph node surgery specimen pathological examination without residual tumor cell
  measure: R0 resection rate
  time frame: Immediately after the surgery
  description: Residual tumor rate
  measure: Objective response rate (ORR)
  time frame: Up to 36 month
  description: ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
  measure: Disease control rate (DCR)
  time frame: Up to 36 month
  description: DCR is defined as the percentage of participants in the analysis population who have a CR, PR or stable disease (SD) per RECIST 1.1.
  measure: Disease-free survival (DFS)
  time frame: 3(5) years after last patient enrolled
  description: Survival without local or systemic recurrence
  measure: Overall survival (OS)
  time frame: Up to 36 month
  description: Overall survival is defined as the duration from date of enrollment to the date of death from any cause.
  measure: Safety: AE
  time frame: Up to 36 month
  description: Safety was defined as the Number of Participants With an Adverse Event
  measure: Change From Baseline in HRQoL Score Using EORTC Quality of Life Questionnaire-Oesophageal Module (QLQ-OES18)
  time frame: Up to 36 month
  description: The EORTC QLQ-OES18 is a disease-specific questionnaire to assess measurements specific to esophageal cancer. It contains 18 items and is based on four subscales-dysphagia, eating, reflux and pain. All items are scored using a four-point scale that offers these response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. A higher score indicates worse level of symptoms. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in HRQoL QLQ-OES18 score in participants will be presented.
  arm group label: Neoadjuvant Anlotinib Combined With Toripalimab and Chemotherapy
  arm group type: Experimental
  description: Toripalimab+ Anlotinib+Albumin-bound paclitaxel+Cisplatin
  intervention type: Drug
  intervention name: Toripalimab
  description: Toripalimab, 240mg, IV., D1, every 3 weeks, 4 cycles.
  arm group label: Neoadjuvant Anlotinib Combined With Toripalimab and Chemotherapy
  other name: JS001
  intervention type: Drug
  intervention name: Anlotinib hydrochloride
  description: Anlotinib Hydrochloride is a capsule in the form of 8 mg ,10 mg and 12 mg, orally, once daily, 2 weeks on/1 week off, every 3 weeks, 4 cycles.
  arm group label: Neoadjuvant Anlotinib Combined With Toripalimab and Chemotherapy
  other name: Anlotinib
  intervention type: Drug
  intervention name: Albumin paclitaxel
  description: Albumin paclitaxel, 200-260 mg/m2, IV., D1, every 3 weeks, 4 cycles.
  arm group label: Neoadjuvant Anlotinib Combined With Toripalimab and Chemotherapy
  other name: Paclitaxel For Injection (Albumin Bound)
  intervention type: Drug
  intervention name: Cisplatin
  description: Cisplatin, 60-75 mg/m2, IV., D1, every 3 weeks, 4 cycles.
  arm group label: Neoadjuvant Anlotinib Combined With Toripalimab and Chemotherapy
  other name: CDDP
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: kaican cai, M.D., PhD
  role: Principal Investigator
  affiliation: Nanfang Hospital, Southern Medical University
  last name: di lu, M.D., PhD
  phone: 13268379321
  email: david_lu1989@163.com
  responsible party type: Sponsor
  mesh term: Carcinoma
  mesh term: Esophageal Neoplasms
  mesh term: Paclitaxel
  mesh term: Albumin-Bound Paclitaxel
  sharing ipd: No