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/NCT06041724</url>
    </required_header>
    <id_info>
      <org_study_id>Fudan-MM003</org_study_id>
      <nct_id>NCT06041724</nct_id>
    </id_info>
    <brief_title>Envafolimab Combined With Recombinant Human Endostatin and First-line Chemotherapy Treat of Advanced Mucosal Melanoma</brief_title>
    <official_title>Single-arm II Phase Study of Envafolimab Combined With Recombinant Human Endostatin and First-line Chemotherapy</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Fudan University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Fudan University</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a phase II, open, single-center study to explore the efficacy and safety of&#xD;
        Envafolimab combined with recombinant human endostatin, temozolomide and cisplatin in the&#xD;
        treatment of mucosal melanin. At the same time, the tissue and peripheral blood samples of&#xD;
        the patients were taken for the determination of PD-L1 expression, ctDNA and other biomarkers&#xD;
        and the results were analyzed to find the predictive factors of prognosis or curative effect.&#xD;
        Patients with advanced mucosal melanoma who met the inclusion criteria but did not meet the&#xD;
        exclusion criteria were enrolled in this study and received 6 cycles of Envafolimab combined&#xD;
        with recombinant human endostatin, temozolomide and cisplatin. Patients without progression&#xD;
        were then maintained with Envafolimab combined with recombinant human endostatin until&#xD;
        disease progression, intolerable adverse reactions, patient death or withdrawal of informed&#xD;
        consent. The longest administration time of recombinant human endostatin was no more than 1&#xD;
        year, and that of Envafolimab was not more than 2 years. The efficacy was evaluated for the&#xD;
        first time at 6 weeks, every 6 weeks for the following year, and then every 12 weeks until&#xD;
        the end of progress or treatment. The examination method was consistent with the baseline; it&#xD;
        was expected to be included in the group for 18 months, and clinical observation until&#xD;
        disease progression and patient death.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 18, 2023</start_date>
    <completion_date type="Anticipated">March 18, 2026</completion_date>
    <primary_completion_date type="Anticipated">September 18, 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>
    </study_design_info>
    <primary_outcome>
      <measure>Progression-free Survival (PFS)</measure>
      <time_frame>12 months</time_frame>
      <description>Time from the date of randomization to the date of progressive disease (PD) or death, whichever occurs first.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Objective Response Rate (ORR)</measure>
      <time_frame>12 months</time_frame>
      <description>ORR was defined as the percentage of participants with measurable lesions achieving a Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) criteria.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease Control Rate (DCR)</measure>
      <time_frame>12 months</time_frame>
      <description>The proportion of participants who achieves a best overall response of CR, PR or stable disease(SD).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Response (DoR)</measure>
      <time_frame>12 months</time_frame>
      <description>The time from the date that response criteria are first met to the date that progressive disease (PD) is objectively documented or death, whichever occurs first.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival (OS)</measure>
      <time_frame>12 months</time_frame>
      <description>OS is defined as the time from enrollment to death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PD-L1 expression from the tissue and peripheral blood samples of the patients</measure>
      <time_frame>baseline (When entering the group)</time_frame>
      <description>The tissue and peripheral blood samples of the patients were taken for the determination of PD-L1 expression, and the results were analyzed to find the predictive factors of prognosis or curative effect.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>ctDNA expression from the tissue and peripheral blood samples of the patients</measure>
      <time_frame>baseline (When entering the group)</time_frame>
      <description>The tissue and peripheral blood samples of the patients were taken for the determination of ctDNA expression, and the results were analyzed to find the predictive factors of prognosis or curative effect.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse Events (AEs) according to CTCAE v5.0.</measure>
      <time_frame>12 months</time_frame>
      <description>Adverse Events (AEs) according to CTCAE v5.0.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">46</enrollment>
    <condition>Advanced Mucosal Melanoma</condition>
    <arm_group>
      <arm_group_label>Envafolimab combined with recombinant human endostatin and first-line chemotherapy</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Envafolimab combined with recombinant human endostatin and first-line chemotherapy</intervention_name>
      <description>Envafolimab: 300mg day1, s.c. Q3W; Recombinant human endostatin: 210mg day1, Intravenous pump for 72 hours, Q3W; Temozolomide: 150 mg/m2 d1-5, i.v. Q3W; Cisplatin: 25 mg/m2 d1-3, i.v. Q3W.&#xD;
  All of the above drugs were used for 6 cycles, and then Envafolimab and recombinant human endostatin continued only in patients with no progression in the first stage until disease progression as defined by RECIST1.1, unacceptable toxicity, withdrawal from the study or death, or no more than 2 years.</description>
      <arm_group_label>Envafolimab combined with recombinant human endostatin and first-line chemotherapy</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age ≥ 18 years old, regardless of gender.&#xD;
  &#xD;
            -  Histology and pathology confirmed advanced mucosal melanoma.&#xD;
  &#xD;
            -  Gene mutation state is not limited, except BRAFV600 mutation.&#xD;
  &#xD;
            -  Has not received first-line treatment for advanced melanoma, and temozolomide and&#xD;
               cisplatin have been used in the adjuvant therapy phase, except that the adjuvant&#xD;
               therapy phase has been over 6 months or more.&#xD;
  &#xD;
            -  Eastern Cancer Cooperation Group (ECOG) physical condition score (PS) 0-1.&#xD;
  &#xD;
            -  The estimated survival time is more than 3 months.&#xD;
  &#xD;
            -  Within 7 days before screening (including 7 days), the laboratory data were required&#xD;
               as follows: neutrophil count ≥ 1.5 × 109 shock L, platelet count ≥ 90 × 109 shock L,&#xD;
               hemoglobin ≥ 90g/L (no blood transfusion within 14 days), serum total bilirubin ≤&#xD;
               1.25x normal upper limit (ULN), ALT and AST ≤ 2.5xULN (patients with liver metastasis&#xD;
               ≤ 5xULN); serum creatinine ≤ 1.25xULN.&#xD;
  &#xD;
            -  Have at least one measurable focus (RECIST1.1 standard).&#xD;
  &#xD;
            -  Subjects (or their legal representatives / guardians) must sign an informed consent&#xD;
               form indicating that they understand the purpose of the study, understand the&#xD;
               necessary procedures for the study, and are willing to participate in the study.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients who have previously used PD-L1 inhibitors, except those who progressed 1 year&#xD;
               after the end of adjuvant therapy of PD-L1 monoclonal antibody;&#xD;
  &#xD;
            -  Allergic to Envafolimab or recombinant human endostatin and experimental&#xD;
               chemotherapeutic drugs;&#xD;
  &#xD;
            -  Received any experimental drugs or antineoplastic drugs within 4 weeks before entering&#xD;
               the group;&#xD;
  &#xD;
            -  There is a risk of bleeding, bleeding events of clinical significance or other taboos&#xD;
               in the use of antivascular drugs;&#xD;
  &#xD;
            -  There is a history of other tumors in the past five years, except for cured cervical&#xD;
               cancer or skin basal cell carcinoma;&#xD;
  &#xD;
            -  There are tumor emergencies that require immediate radiotherapy, such as symptomatic&#xD;
               brain or meningeal metastasis, bone-related events, etc;&#xD;
  &#xD;
            -  Pregnant or lactating women; Fertile women who do not use adequate contraception;&#xD;
  &#xD;
            -  Alcohol or drug addiction;&#xD;
  &#xD;
            -  Patients with active, or history of autoimmune diseases that may recur (e.g. systemic&#xD;
               lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune&#xD;
               thyroid disease, multiple sclerosis, vasculitis, glomerulonephritis, etc.), or&#xD;
               patients at high risk (such as immunosuppressive therapy required for organ&#xD;
               transplants). Except for autoimmune hypothyroidism that requires only hormone&#xD;
               replacement therapy or skin diseases that do not require systemic treatment;&#xD;
  &#xD;
            -  Patients who need to receive systemic corticosteroids (dose equivalent to &gt; 10mg&#xD;
               prednisone / day) or other immunosuppressive drugs within 14 days before enrollment or&#xD;
               during the study. The use of topical or inhaled corticosteroids, or short-term (≤ 7&#xD;
               days) use of glucocorticoids for the prevention or treatment of non-autoimmune and&#xD;
               infrequent allergic diseases;&#xD;
  &#xD;
            -  Important organ failure or other serious diseases, including interstitial pneumonia,&#xD;
               clinically related coronary artery disease, cardiovascular disease or myocardial&#xD;
               infarction, congestive heart failure, unstable angina pectoris, symptomatic&#xD;
               pericardial effusion or unstable arrhythmia within 6 months before admission;&#xD;
  &#xD;
            -  A history of human immunodeficiency virus infection, or other acquired, congenital&#xD;
               immunodeficiency diseases, or a history of organ transplant or stem cell&#xD;
               transplantation;&#xD;
  &#xD;
            -  Patients with active chronic hepatitis B or active hepatitis C. HBV carriers, stable&#xD;
               hepatitis B (DNA titer ≤ 103copies / ml) and cured hepatitis C patients (HCVRNA&#xD;
               negative) can be enrolled in the group;&#xD;
  &#xD;
            -  A history of severe neurological or psychiatric illness; severe infection; active&#xD;
               disseminated intravascular coagulation or other concomitant diseases that, in the&#xD;
               opinion of the researchers, seriously endanger the safety of patients or affect the&#xD;
               completion of the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Zhiguo Luo, M.D</last_name>
      <role>Principal Investigator</role>
      <affiliation>Fudan University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Zhiguo Luo, M.D</last_name>
      <phone>+8621-64175590</phone>
      <phone_ext>8908</phone_ext>
      <email>luozhiguo88@163.com</email>
    </overall_contact>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 12, 2023</study_first_submitted>
    <study_first_submitted_qc>September 15, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 18, 2023</study_first_posted>
    <last_update_submitted>September 15, 2023</last_update_submitted>
    <last_update_submitted_qc>September 15, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Fudan University</investigator_affiliation>
      <investigator_full_name>Zhiguo Luo, MD, PhD</investigator_full_name>
      <investigator_title>Professor and Chief Surgeon</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Melanoma</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Endostatins</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/NCT06041724
  org study id: Fudan-MM003
  nct id: NCT06041724
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This is a phase II, open, single-center study to explore the efficacy and safety of
        Envafolimab combined with recombinant human endostatin, temozolomide and cisplatin in the
        treatment of mucosal melanin. At the same time, the tissue and peripheral blood samples of
        the patients were taken for the determination of PD-L1 expression, ctDNA and other biomarkers
        and the results were analyzed to find the predictive factors of prognosis or curative effect.
        Patients with advanced mucosal melanoma who met the inclusion criteria but did not meet the
        exclusion criteria were enrolled in this study and received 6 cycles of Envafolimab combined
        with recombinant human endostatin, temozolomide and cisplatin. Patients without progression
        were then maintained with Envafolimab combined with recombinant human endostatin until
        disease progression, intolerable adverse reactions, patient death or withdrawal of informed
        consent. The longest administration time of recombinant human endostatin was no more than 1
        year, and that of Envafolimab was not more than 2 years. The efficacy was evaluated for the
        first time at 6 weeks, every 6 weeks for the following year, and then every 12 weeks until
        the end of progress or treatment. The examination method was consistent with the baseline; it
        was expected to be included in the group for 18 months, and clinical observation until
        disease progression and patient death.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Progression-free Survival (PFS)
  time frame: 12 months
  description: Time from the date of randomization to the date of progressive disease (PD) or death, whichever occurs first.
  measure: Objective Response Rate (ORR)
  time frame: 12 months
  description: ORR was defined as the percentage of participants with measurable lesions achieving a Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) criteria.
  measure: Disease Control Rate (DCR)
  time frame: 12 months
  description: The proportion of participants who achieves a best overall response of CR, PR or stable disease(SD).
  measure: Duration of Response (DoR)
  time frame: 12 months
  description: The time from the date that response criteria are first met to the date that progressive disease (PD) is objectively documented or death, whichever occurs first.
  measure: Overall Survival (OS)
  time frame: 12 months
  description: OS is defined as the time from enrollment to death from any cause.
  measure: PD-L1 expression from the tissue and peripheral blood samples of the patients
  time frame: baseline (When entering the group)
  description: The tissue and peripheral blood samples of the patients were taken for the determination of PD-L1 expression, and the results were analyzed to find the predictive factors of prognosis or curative effect.
  measure: ctDNA expression from the tissue and peripheral blood samples of the patients
  time frame: baseline (When entering the group)
  description: The tissue and peripheral blood samples of the patients were taken for the determination of ctDNA expression, and the results were analyzed to find the predictive factors of prognosis or curative effect.
  measure: Adverse Events (AEs) according to CTCAE v5.0.
  time frame: 12 months
  description: Adverse Events (AEs) according to CTCAE v5.0.
  arm group label: Envafolimab combined with recombinant human endostatin and first-line chemotherapy
  arm group type: Experimental
  intervention type: Drug
  intervention name: Envafolimab combined with recombinant human endostatin and first-line chemotherapy
  description: Envafolimab: 300mg day1, s.c. Q3W; Recombinant human endostatin: 210mg day1, Intravenous pump for 72 hours, Q3W; Temozolomide: 150 mg/m2 d1-5, i.v. Q3W; Cisplatin: 25 mg/m2 d1-3, i.v. Q3W.
  All of the above drugs were used for 6 cycles, and then Envafolimab and recombinant human endostatin continued only in patients with no progression in the first stage until disease progression as defined by RECIST1.1, unacceptable toxicity, withdrawal from the study or death, or no more than 2 years.
  arm group label: Envafolimab combined with recombinant human endostatin and first-line chemotherapy
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Zhiguo Luo, M.D
  role: Principal Investigator
  affiliation: Fudan University
  last name: Zhiguo Luo, M.D
  phone: +8621-64175590
  phone ext: 8908
  email: luozhiguo88@163.com
  responsible party type: Principal Investigator
  investigator affiliation: Fudan University
  investigator full name: Zhiguo Luo, MD, PhD
  investigator title: Professor and Chief Surgeon
  mesh term: Melanoma
  mesh term: Endostatins
  sharing ipd: No