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/NCT06019468</url>
    </required_header>
    <id_info>
      <org_study_id>STAR005</org_study_id>
      <nct_id>NCT06019468</nct_id>
    </id_info>
    <brief_title>Neoadjuvant Treatment For Locally Advanced Thymic Cancer</brief_title>
    <official_title>Clinical Study of Envolizumab Combined With Radiotherapy for Neoadjuvant Treatment of Locally Advanced Thymic Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Shanghai Pulmonary Hospital, Shanghai, China</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Shanghai Pulmonary Hospital, Shanghai, China</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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The aims of this study are to verify the feasibility, effectiveness, and safety of the&#xD;
        combination of enrolizumab and radiotherapy for neoadjuvant treatment for locally advanced&#xD;
        thymic carcinoma, and to provide recommendations for the establishment of unified evaluation&#xD;
        criteria for the neoadjuvant therapy of thymic cancer by evaluating the pathological&#xD;
        remission status of thymic cancer specimens after neoadjuvant treatment.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        For patients with locally advanced thymic carcinoma, it is often difficult to perform radical&#xD;
        resection. Numerous studies have reported that neoadjuvant therapy can improve the surgical&#xD;
        resection rate of thymic tumors by reducing the extent of tumor invasion and eliminating&#xD;
        small metastatic lesions, thereby improving patient survival. However, the efficacy of&#xD;
        neoadjuvant immunotherapy combined with chemotherapy is limited. This study intends to&#xD;
        conduct a single-arm, phase II clinical trial of neoadjuvant immunotherapy combined with&#xD;
        radiotherapy for locally advanced thymic carcinoma to verify the feasibility and safety of&#xD;
        neoadjuvant immunotherapy combined with radiotherapy. Meanwhile, the investigators evaluate&#xD;
        the pathological remission of postoperative specimens to provide recommendations for&#xD;
        establishing pathological evaluation criteria for neoadjuvant therapy for thymic carcinoma.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">September 4, 2023</start_date>
    <completion_date type="Anticipated">December 30, 2025</completion_date>
    <primary_completion_date type="Anticipated">August 30, 2025</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>
      <masking_description>No Masking</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>objective response rate（ORR）</measure>
      <time_frame>24 hour</time_frame>
      <description>ORR was defined as the best overall response (BoR), the proportion of participants in complete and partial response among the number of participants in each treatment group who received at least one medication.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Disease control rate（DCR）</measure>
      <time_frame>24 hours</time_frame>
      <description>DCR is defined as the proportion of imaging findings of CR, PR, and stable disease (SD) in all subjects evaluated according to RECIST V1.1 after completing neoadjuvant immunotherapy combined with radiotherapy</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Radical resection rate（R0）</measure>
      <time_frame>24 hours</time_frame>
      <description>Pathological evaluation of the tumor margin, and based on whether the margin is gross or microscopic positive, it is divided into radical resection (R0), microscopic residual lesion (R1), or gross residual lesion (R2)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pathological remission rate</measure>
      <time_frame>7 days</time_frame>
      <description>Conduct pathological evaluation based on postoperative specimens to evaluate the percentage of surviving tumor cells, necrosis, and interstitial components in the original tumor bed area.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>disease-free survival（DFS）</measure>
      <time_frame>5 years</time_frame>
      <description>The time interval between receiving surgical treatment and tumor recurrence or death due to tumor progression</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>overall survival（OS）</measure>
      <time_frame>5 years</time_frame>
      <description>The time interval between receiving surgical treatment and the patient's death due to any reason, and the patient is still alive during the final follow-up, with the survival time ending at the last follow-up.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">25</enrollment>
    <condition>Thymic Carcinoma</condition>
    <arm_group>
      <arm_group_label>Neoadjuvant immunotherapy combined with radiotherapy</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Treatment arms comprise 10-20 cycles of radiotherapy and 2-4 cycles of maintenance therapy with Envolizumab</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Envolizumab combined with radiotherapy</intervention_name>
      <description>Application of Envolizumab combined with radiotherapy for neoadjuvant treatment of locally advanced thymic cancer. Firstly, 20-40Gy radiation therapy was administered 10-20 times. Within one week after the start of radiation therapy, Envolizumab (300 mg, D1, Q3W, subcutaneous injection) was administered. Immunotherapy was maintained for 2-4 cycles, and surgery was performed after evaluation by the attending physician.</description>
      <arm_group_label>Neoadjuvant immunotherapy combined with radiotherapy</arm_group_label>
      <other_name>KN035</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Pathologically confirmed as thymic carcinoma;&#xD;
  &#xD;
            2. Clinical staging III-IVA (TNM staging system), non-myasthenia gravis (MG) patients,&#xD;
               expected to undergo surgical resection;&#xD;
  &#xD;
            3. On the day when the subject signs the informed consent form, they are ≥ 18 years old&#xD;
               and&lt;75 years old, regardless of gender;&#xD;
  &#xD;
            4. The subjects are able to understand the informed consent form, voluntarily&#xD;
               participate, and sign the informed consent form;&#xD;
  &#xD;
            5. Subjects who have not received any anti-thymic tumor treatment in the past, including&#xD;
               but not limited to systemic chemotherapy, radiotherapy, or immunotherapy (only those&#xD;
               who have received traditional Chinese medicine treatment for anti-tumor indications&#xD;
               are allowed to be included, and a cleaning period of at least 2 weeks is required);&#xD;
  &#xD;
            6. At least 1 measurable lesion (according to the solid tumor efficacy evaluation&#xD;
               standard RECIST V1.1);&#xD;
  &#xD;
            7. Physical fitness score of 0 or 1 (ECOG scoring system of the Eastern Cancer&#xD;
               Collaborative Group in the United States);&#xD;
  &#xD;
            8. Female subjects with fertility must have a negative serum pregnancy test within 7 days&#xD;
               before the first administration;&#xD;
  &#xD;
            9. Female subjects with fertility or male subjects with partners with fertility agree to&#xD;
               use efficient contraceptive measures (with an annual failure rate of less than 1%)&#xD;
               from 7 days before the first administration until 24 weeks after the end of&#xD;
               administration;&#xD;
  &#xD;
           10. The main organ functions within 7 days before the first administration meet the&#xD;
               following standards:&#xD;
  &#xD;
                 1. Bone marrow function: hemoglobin ≥ 10.0 g/dL (no blood transfusion received&#xD;
                    within 28 days before hemoglobin test), absolute neutrophil count ≥ 1.5 × 109/L,&#xD;
                    platelet count ≥ 100 × 109/L (no platelet transfusion or IL-11 treatment received&#xD;
                    within 14 days prior to platelet count test);&#xD;
  &#xD;
                 2. Coagulation function: INR and PT&lt;1.5 × ULN, APTT ≤ 1.5 × ULN;&#xD;
  &#xD;
                 3. Liver function: transaminases (ALT and AST) ≤ 2.5 × ULN; Total bilirubin ≤ 1.5 ×&#xD;
                    ULN (total bilirubin ≤ 2.5 in subjects with Gilbert's syndrome or liver&#xD;
                    metastasis) × ULN);&#xD;
  &#xD;
                 4. Renal function: serum creatinine clearance rate ≥ 60 mL/min (calculated according&#xD;
                    to Cockcroft Fault formula);&#xD;
  &#xD;
                 5. Adequate lung function: According to the doctor's judgment, lung function can&#xD;
                    meet the requirements of thymectomy surgery.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Pathologically confirmed as a thymic neuroendocrine tumor;&#xD;
  &#xD;
            2. Subjects who have undergone major surgical treatment (such as abdominal or thoracic&#xD;
               surgery; excluding diagnostic puncture or peripheral vascular pathway replacement&#xD;
               surgery) or have not recovered from surgical treatment within 28 days before the&#xD;
               administration of this trial;&#xD;
  &#xD;
            3. Within 14 days before the first administration of this study, systemic corticosteroids&#xD;
               (≥ 10 mg/day prednisone, or equivalent amounts of other corticosteroids) or&#xD;
               immunosuppressive therapy are required for 7 consecutive days; Excluding inhalation or&#xD;
               local application of hormones, or receiving physiological replacement doses of hormone&#xD;
               therapy due to adrenal insufficiency; Allow short-term (&lt;7 days) use of&#xD;
               corticosteroids for prevention (such as contrast agent allergies) or treatment of&#xD;
               non-autoimmune diseases (such as delayed hypersensitivity reactions caused by exposure&#xD;
               to allergens);&#xD;
  &#xD;
            4. Received live vaccines (including attenuated live vaccines) within 28 days prior to&#xD;
               administration in this study;&#xD;
  &#xD;
            5. Previously or currently suffering from interstitial pneumonia/lung disease that&#xD;
               requires systemic hormone therapy;&#xD;
  &#xD;
            6. Previously or currently suffering from autoimmune diseases, including but not limited&#xD;
               to Crohn's disease, ulcerative colitis, systemic lupus erythematosus, sarcoidosis,&#xD;
               Wegener syndrome (granulomatosis of vasculitis, Graves disease, rheumatoid arthritis,&#xD;
               pituitary inflammation, uveitis), autoimmune hepatitis, systemic sclerosis&#xD;
               (scleroderma, etc.), Hashimoto's thyroiditis (exceptions see below), autoimmune&#xD;
               vasculitis Autoimmune neuropathy (Guillain Barre syndrome), etc. The following cases&#xD;
               are excluded: type I diabetes, hypothyroidism with stable hormone replacement therapy&#xD;
               (including hypothyroidism caused by autoimmune thyroid disease), psoriasis or vitiligo&#xD;
               without systemic treatment;&#xD;
  &#xD;
            7. Other malignant tumors were combined within 5 years before the first administration,&#xD;
               excluding cured skin squamous cell carcinoma, basal cell carcinoma, non-muscle&#xD;
               invasive bladder cancer, localized low-risk prostate (defined as stage ≤ T2a, Gleason&#xD;
               score ≤ 6, and PSA ≤ 10ng/mL at the time of diagnosis of prostate cancer (if measured,&#xD;
               patients who have received radical treatment and have no PSA biochemical relapse can&#xD;
               participate in this study), and in situ cervical/breast cancer;&#xD;
  &#xD;
            8. Have uncontrolled heart, kidney, gastrointestinal tract, infectious diseases and other&#xD;
               complications;&#xD;
  &#xD;
            9. Previous history of allogeneic bone marrow or organ transplantation;;&#xD;
  &#xD;
           10. Previously treated with any antibody/drug (immune checkpoint) targeting T cell&#xD;
               co-regulatory proteins, such as anti PD (L) 1, CTLA-4, 4-1BB, LAG 3, TIM 3, or anti&#xD;
               CD127; Previously received anti-tumor vaccine treatment&#xD;
  &#xD;
           11. Previous history of allergic reactions to antibody-based drugs and intolerance (≥&#xD;
               Level 3 NCI-CTCAE V5.0); Any past history of rapid allergic reactions and&#xD;
               uncontrollable asthma (i.e. uncontrollable asthma symptoms of 3 or more of the 3 or&#xD;
               more characteristics of partially controlled asthma); Previous obvious allergies to&#xD;
               drugs (such as severe allergic reactions, immune-mediated hepatotoxicity,&#xD;
               immune-mediated thrombocytopenia or anemia);&#xD;
  &#xD;
           12. Pregnant and/or lactating women;&#xD;
  &#xD;
           13. Other situations that may affect the safety or compliance of drug treatment in this&#xD;
               study, including but not limited to mental illness, uncontrolled large amounts of&#xD;
               serous fluid accumulation, or subjects who require repeated drainage (recurrence&#xD;
               within 2 weeks after intervention) with moderate to large amounts of serous fluid&#xD;
               accumulation, cachexia, etc.&#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>Deping Zhao, MD,PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Shanghai Pulmonary Hospital, School of Medicine, Tongji University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Juemin Yu</last_name>
      <phone>+8615927548511</phone>
      <email>yujm96@163.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Deping Zhao, MD,PhD</last_name>
      <phone>+8613701816883</phone>
      <email>zdp1992@163.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Shanghai Pulmonary Hospital</name>
        <address>
          <city>Shanghai</city>
          <state>Shanghai</state>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Deping Zhao</last_name>
        <email>zdp1992@163.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 25, 2023</study_first_submitted>
    <study_first_submitted_qc>August 30, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 31, 2023</study_first_posted>
    <last_update_submitted>September 3, 2023</last_update_submitted>
    <last_update_submitted_qc>September 3, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 6, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Shanghai Pulmonary Hospital, Shanghai, China</investigator_affiliation>
      <investigator_full_name>Deping Zhao</investigator_full_name>
      <investigator_title>Administrative Director of Thoracic Surgery Department</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Thymoma</mesh_term>
      <mesh_term>Thymus Neoplasms</mesh_term>
    </condition_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/NCT06019468
  org study id: STAR005
  nct id: NCT06019468
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  The aims of this study are to verify the feasibility, effectiveness, and safety of the
        combination of enrolizumab and radiotherapy for neoadjuvant treatment for locally advanced
        thymic carcinoma, and to provide recommendations for the establishment of unified evaluation
        criteria for the neoadjuvant therapy of thymic cancer by evaluating the pathological
        remission status of thymic cancer specimens after neoadjuvant treatment.
  For patients with locally advanced thymic carcinoma, it is often difficult to perform radical
        resection. Numerous studies have reported that neoadjuvant therapy can improve the surgical
        resection rate of thymic tumors by reducing the extent of tumor invasion and eliminating
        small metastatic lesions, thereby improving patient survival. However, the efficacy of
        neoadjuvant immunotherapy combined with chemotherapy is limited. This study intends to
        conduct a single-arm, phase II clinical trial of neoadjuvant immunotherapy combined with
        radiotherapy for locally advanced thymic carcinoma to verify the feasibility and safety of
        neoadjuvant immunotherapy combined with radiotherapy. Meanwhile, the investigators evaluate
        the pathological remission of postoperative specimens to provide recommendations for
        establishing pathological evaluation criteria for neoadjuvant therapy for thymic carcinoma.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  masking description: No Masking
  measure: objective response rate（ORR）
  time frame: 24 hour
  description: ORR was defined as the best overall response (BoR), the proportion of participants in complete and partial response among the number of participants in each treatment group who received at least one medication.
  measure: Disease control rate（DCR）
  time frame: 24 hours
  description: DCR is defined as the proportion of imaging findings of CR, PR, and stable disease (SD) in all subjects evaluated according to RECIST V1.1 after completing neoadjuvant immunotherapy combined with radiotherapy
  measure: Radical resection rate（R0）
  time frame: 24 hours
  description: Pathological evaluation of the tumor margin, and based on whether the margin is gross or microscopic positive, it is divided into radical resection (R0), microscopic residual lesion (R1), or gross residual lesion (R2)
  measure: Pathological remission rate
  time frame: 7 days
  description: Conduct pathological evaluation based on postoperative specimens to evaluate the percentage of surviving tumor cells, necrosis, and interstitial components in the original tumor bed area.
  measure: disease-free survival（DFS）
  time frame: 5 years
  description: The time interval between receiving surgical treatment and tumor recurrence or death due to tumor progression
  measure: overall survival（OS）
  time frame: 5 years
  description: The time interval between receiving surgical treatment and the patient's death due to any reason, and the patient is still alive during the final follow-up, with the survival time ending at the last follow-up.
  arm group label: Neoadjuvant immunotherapy combined with radiotherapy
  arm group type: Experimental
  description: Treatment arms comprise 10-20 cycles of radiotherapy and 2-4 cycles of maintenance therapy with Envolizumab
  intervention type: Other
  intervention name: Envolizumab combined with radiotherapy
  description: Application of Envolizumab combined with radiotherapy for neoadjuvant treatment of locally advanced thymic cancer. Firstly, 20-40Gy radiation therapy was administered 10-20 times. Within one week after the start of radiation therapy, Envolizumab (300 mg, D1, Q3W, subcutaneous injection) was administered. Immunotherapy was maintained for 2-4 cycles, and surgery was performed after evaluation by the attending physician.
  arm group label: Neoadjuvant immunotherapy combined with radiotherapy
  other name: KN035
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Deping Zhao, MD,PhD
  role: Principal Investigator
  affiliation: Shanghai Pulmonary Hospital, School of Medicine, Tongji University
  last name: Juemin Yu
  phone: +8615927548511
  email: yujm96@163.com
  last name: Deping Zhao, MD,PhD
  phone: +8613701816883
  email: zdp1992@163.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Shanghai Pulmonary Hospital, Shanghai, China
  investigator full name: Deping Zhao
  investigator title: Administrative Director of Thoracic Surgery Department
  mesh term: Thymoma
  mesh term: Thymus Neoplasms
  sharing ipd: No