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/NCT06030934</url>
    </required_header>
    <id_info>
      <org_study_id>SMA-GC-002</org_study_id>
      <nct_id>NCT06030934</nct_id>
    </id_info>
    <brief_title>Study of The Second-line Treatment of Advanced Gastric / Gastroesophageal Junction Adenocarcinoma With Envafolimab and Lenvatinib Combined With Paclitaxel-albumin</brief_title>
    <official_title>An Open and Exploratory Study of The Second-line Treatment of Advanced Gastric / Gastroesophageal Junction Adenocarcinoma With Envafolimab and Lenvatinib Combined With Paclitaxel-albumin</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 study is an open, exploratory clinical study. Eligible patients with advanced&#xD;
        second-line gastric/gastroesophageal junction adenocarcinoma signed an informed consent form,&#xD;
        were screened for enrollment, and were entered into Group A (non-immune retreatment&#xD;
        group-patients who had failed previous first-line treatment with standard chemotherapy) and&#xD;
        Group B (immune retreatment-patients who had obtained SD and above with best efficacy of&#xD;
        previous first-line treatment with PD-1 antibody) based on whether they had received previous&#xD;
        first-line treatment with PD-1 antibody. All patients received a combination of envafolimab&#xD;
        and lenvatinib in combination with paclitaxel-albumin and were treated until disease&#xD;
        progression, withdrawal of informed consent by the subject, loss to follow-up, and death,&#xD;
        where treatment did not exceed 2 years. Clinical oncologic imaging assessments were performed&#xD;
        using iRECIST every 8 weeks during treatment; safety assessments were performed using CTCAE&#xD;
        5.0, and adverse events were recorded throughout the study up to 30 days after the end of&#xD;
        treatment.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Enrolling by invitation</overall_status>
    <start_date type="Actual">October 24, 2022</start_date>
    <completion_date type="Anticipated">September 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">November 1, 2024</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_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>
    </primary_outcome>
    <secondary_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>
    </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>20 months</time_frame>
      <description>OS is defined as the time from enrollment to death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse Events (AEs)</measure>
      <time_frame>12 months</time_frame>
      <description>Adverse Events (AEs) according to CTCAE v5.0</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Gastric / Gastroesophageal Junction Adenocarcinoma</condition>
    <arm_group>
      <arm_group_label>Patients who have failed previous standard chemotherapy</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Patients with SD or above obtained by previous first-line PD-1 antibody therapy</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>envafolimab and lenvatinib combined with paclitaxel-albumin</intervention_name>
      <description>envafolimab: 200mg d1,15 s.c. Q4W; lenvatinib: 8mg (&lt;60kg) or 12mg (≥60kg) p.o. Q.d.; paclitaxel-albumin: 100 mg/m2 d1,8,15 stop for one week, i.v. Q4W</description>
      <arm_group_label>Patients who have failed previous standard chemotherapy</arm_group_label>
      <arm_group_label>Patients with SD or above obtained by previous first-line PD-1 antibody therapy</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Signed written informed consent prior to enrollment.&#xD;
  &#xD;
            -  Age 18-80 years.&#xD;
  &#xD;
            -  Negative for HER2&#xD;
  &#xD;
            -  Diagnosis confirmed by histological examination and/or cytological examination&#xD;
               combined with imaging assessment of advanced metastatic gastric/gastroesophageal&#xD;
               junction adenocarcinoma.&#xD;
  &#xD;
            -  Failure of previous first-line therapy. Group A (non-immune retreatment): patients who&#xD;
               have failed prior chemotherapy with first-line standard therapy. Group B (immune&#xD;
               retreatment): patients who received previous first-line PD-1 antibody therapy with&#xD;
               optimal efficacy SD and on.&#xD;
  &#xD;
            -  ECOG score: 0 to 1.&#xD;
  &#xD;
            -  At least one measurable lesion (≥10 mm long diameter on CT scan for non-lymph node&#xD;
               lesions and ≥15 mm short diameter on CT scan for lymph node lesions according to&#xD;
               iRECIST criteria).&#xD;
  &#xD;
            -  Adequate organ function with.&#xD;
  &#xD;
                 1. Routine blood: Absolute Neutrophil Count (ANC) 1.5 × 109/L, Platelets (Platelet,&#xD;
                    PLT) ≥ 70 × 109/L, Hemoglobin (HGB) ≥ 90 g/L.&#xD;
  &#xD;
                 2. Liver function: Total Bilirubin (TBIL) ≤ 1.5 × Upper Limit of Normal Value (ULN);&#xD;
                    Alanine Aminotransferase (ALT) and Aspartate Transferase (AST) ≤3×ULN; serum&#xD;
                    albumin ≥28 g/L; Alkaline Phosphatase (ALP) ≤5×ULN; after conventional&#xD;
                    hepatoprotective treatment meeting the above criteria, and can be stable for at&#xD;
                    least 1 week after evaluation by the investigator can be enrolled.&#xD;
  &#xD;
                 3. Renal function: Creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/mi&#xD;
                    (applying the standard Cockcroft-Gault formula).&#xD;
  &#xD;
                 4. Coagulation function: International Normalized Ratio (INR) ≤ 1.5 /PT ≤ 1.5 × ULN,&#xD;
                    aPTT ≤ 1.5 × ULN; if the subject is receiving anticoagulation therapy, as long as&#xD;
                    PT and INR are within the range drawn up by anticoagulant drugs.&#xD;
  &#xD;
            -  A predicted survival of ≥ 3 months.&#xD;
  &#xD;
            -  Female patients must be non-pregnant and non-lactating and are required to use a&#xD;
               medically approved form of contraception (e.g., IUD, pill or condom) during study&#xD;
               treatment and for at least 120 days after study completion, and are not allowed to&#xD;
               donate eggs to another person or freeze them for fertilization and propagation during&#xD;
               this period.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Symptomatic brain metastases.&#xD;
  &#xD;
            -  Known MSI-H/dMMR.&#xD;
  &#xD;
            -  A prior history of a primary tumor outside of the gastric/gastroesophageal junction&#xD;
  &#xD;
            -  Active autoimmune disease or autoimmune disease with potential for recurrence such as,&#xD;
               but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis,&#xD;
               enterocolitis, hepatitis, pituitary inflammation, vasculitis, nephritis,&#xD;
               hyperthyroidism, hypothyroidism, previous thyroid surgery cannot be included; subjects&#xD;
               with vitiligo or complete remission of asthma in childhood and adult who do not&#xD;
               require any intervention afterwards can be included; subjects with asthma requiring&#xD;
               medical intervention with bronchodilators cannot be included.&#xD;
  &#xD;
            -  Subjects with any severe and/or uncontrolled disease. including.&#xD;
  &#xD;
                 1. Poorly controlled blood pressure (systolic blood pressure ≥ 150 mmHg or diastolic&#xD;
                    blood pressure ≥ 100 mmHg); poorly controlled diabetes (fasting blood glucose&#xD;
                    [FBG] &gt; 10 mmol/L)&#xD;
  &#xD;
                 2. Having ≥ grade 2 myocardial ischemia or myocardial infarction, arrhythmia (QTc ≥&#xD;
                    470ms) and ≥ grade 2 congestive heart failure (New York Heart Association [NYHA]&#xD;
                    classification)&#xD;
  &#xD;
                 3. Active or uncontrolled severe infection (≥ CTCAE grade 2 infection) requiring&#xD;
                    systemic antibacterial, antifungal or antiviral therapy, including tuberculosis&#xD;
                    infection&#xD;
  &#xD;
                 4. Active hepatitis (transaminases do not meet the inclusion criteria, hepatitis B&#xD;
                    reference: HBV DNA ≥ 2000 IU/ml or ≥ 104 copies/ml; hepatitis C reference: HCV&#xD;
                    RNA ≥ 2000 IU/ml or ≥ 104 copies/ml; after nucleotide based antiviral therapy&#xD;
                    below the above criteria, can be enrolled); chronic hepatitis B virus carriers&#xD;
                    with HBV DNA &lt; 104 IU/ml, who must receive concomitant antiviral therapy during&#xD;
                    the trial to be enrolled.&#xD;
  &#xD;
                 5. Those with renal failure requiring hemodialysis or peritoneal dialysis.&#xD;
  &#xD;
                 6. Those with a history of immunodeficiency, including HIV-positive or suffering&#xD;
                    from other acquired or congenital immunodeficiency diseases, or a history of&#xD;
                    organ transplantation&#xD;
  &#xD;
                 7. Active autoimmune disease requiring systemic therapy (e.g., use of&#xD;
                    disease-relieving drugs, corticosteroids, or immunosuppressive agents) within 2&#xD;
                    years prior to the start of study treatment, except for replacement therapies&#xD;
                    (e.g., thyroxine, insulin, or physiologic corticosteroids for adrenal or&#xD;
                    pituitary insufficiency); receiving systemic glucocorticoid therapy or any other&#xD;
                    form of immunosuppressive therapy. Doses &gt;10 mg/day of prednisone or other&#xD;
                    equivalent hormone and within 2 weeks of the first dose and still continuing&#xD;
  &#xD;
                 8. Those with a history of active tuberculosis&#xD;
  &#xD;
                 9. Those who fail to control and still require repeated drainage of ascites,&#xD;
                    pericardial effusion, pleural effusion.&#xD;
  &#xD;
            -  Research treatment related to.&#xD;
  &#xD;
                 1. Patients who have undergone major organ transplantation&#xD;
  &#xD;
                 2. Those who have undergone major surgical treatment, incisional biopsy or&#xD;
                    significant traumatic injury within 28 days prior to the start of study&#xD;
                    treatment; or have a long-standing untreated wound or fracture&#xD;
  &#xD;
                 3. History of live attenuated vaccination within 14 days prior to the start of study&#xD;
                    treatment or planned live attenuated vaccination during the study&#xD;
  &#xD;
                 4. History of severe hypersensitivity reactions following the use of monoclonal&#xD;
                    antibodies; known hypersensitivity to active ingredients or excipients such as&#xD;
                    envafolimab, lenvatinib, etc., of this study drug&#xD;
  &#xD;
                 5. Those who are participating or have participated in other clinical studies within&#xD;
                    4 weeks prior to the start of the study&#xD;
  &#xD;
            -  Those with a history of severe allergy.&#xD;
  &#xD;
            -  Women who are pregnant or breastfeeding&#xD;
  &#xD;
            -  At risk for bleeding, or with coagulation disorders, or undergoing thrombolytic&#xD;
               therapy&#xD;
  &#xD;
            -  Those with a history of psychotropic substance abuse and unable to abstain or with&#xD;
               psychiatric disorders&#xD;
  &#xD;
            -  Subjects who, in the judgment of the investigator, have a concomitant disease that&#xD;
               seriously jeopardizes the safety of the subject or interferes with the completion of&#xD;
               the study, or subjects for whom other reasons are deemed to exist that make them&#xD;
               unsuitable for enrollment In the judgment of the investigator, subjects who, in the&#xD;
               judgment of the investigator, have a concomitant disease that seriously jeopardizes&#xD;
               the safety of the subject or interferes with the completion of the study, or subjects&#xD;
               for whom other reasons are deemed to exist that make them unsuitable for enrollment&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Weijian Guo, M.D</last_name>
      <role>Principal Investigator</role>
      <affiliation>Fudan University</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Fudan University Cancer Hospital</name>
        <address>
          <city>Shanghai</city>
          <state>Shanghai</state>
          <zip>200032</zip>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 3, 2023</study_first_submitted>
    <study_first_submitted_qc>September 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 11, 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 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Fudan University</investigator_affiliation>
      <investigator_full_name>Weijian Guo</investigator_full_name>
      <investigator_title>Director of Department of Medical Gastrointestinal Oncology</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Adenocarcinoma</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>Lenvatinib</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/NCT06030934
  org study id: SMA-GC-002
  nct id: NCT06030934
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This study is an open, exploratory clinical study. Eligible patients with advanced
        second-line gastric/gastroesophageal junction adenocarcinoma signed an informed consent form,
        were screened for enrollment, and were entered into Group A (non-immune retreatment
        group-patients who had failed previous first-line treatment with standard chemotherapy) and
        Group B (immune retreatment-patients who had obtained SD and above with best efficacy of
        previous first-line treatment with PD-1 antibody) based on whether they had received previous
        first-line treatment with PD-1 antibody. All patients received a combination of envafolimab
        and lenvatinib in combination with paclitaxel-albumin and were treated until disease
        progression, withdrawal of informed consent by the subject, loss to follow-up, and death,
        where treatment did not exceed 2 years. Clinical oncologic imaging assessments were performed
        using iRECIST every 8 weeks during treatment; safety assessments were performed using CTCAE
        5.0, and adverse events were recorded throughout the study up to 30 days after the end of
        treatment.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  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: 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: 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: 20 months
  description: OS is defined as the time from enrollment to death from any cause.
  measure: Adverse Events (AEs)
  time frame: 12 months
  description: Adverse Events (AEs) according to CTCAE v5.0
  arm group label: Patients who have failed previous standard chemotherapy
  arm group type: Experimental
  arm group label: Patients with SD or above obtained by previous first-line PD-1 antibody therapy
  arm group type: Experimental
  intervention type: Drug
  intervention name: envafolimab and lenvatinib combined with paclitaxel-albumin
  description: envafolimab: 200mg d1,15 s.c. Q4W; lenvatinib: 8mg (<60kg) or 12mg (≥60kg) p.o. Q.d.; paclitaxel-albumin: 100 mg/m2 d1,8,15 stop for one week, i.v. Q4W
  arm group label: Patients who have failed previous standard chemotherapy
  arm group label: Patients with SD or above obtained by previous first-line PD-1 antibody therapy
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  healthy volunteers: No
  last name: Weijian Guo, M.D
  role: Principal Investigator
  affiliation: Fudan University
  facility: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Fudan University
  investigator full name: Weijian Guo
  investigator title: Director of Department of Medical Gastrointestinal Oncology
  mesh term: Adenocarcinoma
  mesh term: Esophageal Neoplasms
  mesh term: Paclitaxel
  mesh term: Lenvatinib
  sharing ipd: No