<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/NCT04453930</url>
  </required_header>
  <id_info>
    <org_study_id>HS-2195</org_study_id>
    <nct_id>NCT04453930</nct_id>
  </id_info>
  <brief_title>A Study of Sequential Therapy of Camrelizumab Combined With Chemotherapy（Irinotecan Plus Platinum）and With Apatinib in Participants With Untreated Advanced Small Cell Lung Cancer（SCLC）</brief_title>
  <official_title>A Single-arm，Open Lable Study of Sequential Therapy of Camrelizumab Combined With Chemotherapy（Irinotecan Plus Platinum）and With Apatinib in Participants With Untreated Advanced Small Cell Lung Cancer（SCLC）</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking Union Medical College Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peking Union Medical College Hospital</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>
      This single arm, open label, single center, prospective study was designed to evaluate the&#xD;
      safety and efficacy of Sequential Therapy of Camrelizumab (humanized monoclonal antibody&#xD;
      against Programmed death 1 [PD-1] ) in combination with Chemotherapy（Irinotecan plus&#xD;
      Platinum）and with Apatinib (selective Vascular Endothelial Growth Factor Receptor 2(VEGFR-2)&#xD;
      tyrosine kinase inhibitor [TKI]) in chemotherapy-naive participants with SCLC. Participants&#xD;
      will receive Camrelizumab + Irinotecan + Platinum on 21-day cycles for 4-6 cycles in the&#xD;
      induction phase followed by maintenance with Camrelizumab + Apatinib until progressive&#xD;
      disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid&#xD;
      Tumors Version 1.1 (RECIST v1.1). Treatment can be continued until persistent radiographic PD&#xD;
      or symptomatic deterioration.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 8, 2020</start_date>
  <completion_date type="Anticipated">June 2023</completion_date>
  <primary_completion_date type="Anticipated">June 2023</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) as assessed by RECIST 1.1</measure>
    <time_frame>From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years.</time_frame>
    <description>PFS is defined as the time from date of enrollment to the date of the first documentation of progressive disease (PD) or death from any cause, whichever occurs first per RECIST 1.1.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Duration of Overall Survival (OS)</measure>
    <time_frame>From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years.</time_frame>
    <description>OS is defined as the time from date of enrollment to date of death from any cause.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR) as assessed by RECIST 1.1</measure>
    <time_frame>through study completion, an average of 2 year.</time_frame>
    <description>DCR is defined as the percentage of participants in the analysis population who have a CR, PR or stable disease per RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) as assessed by RECIST 1.1</measure>
    <time_frame>through study completion, an average of 2 year.</time_frame>
    <description>ORR is defined as the percentage of participants in the analysis population who have a Complete Response(CR) or a Partial Response(PR) per RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1</measure>
    <time_frame>through study completion, an average of 2 year.</time_frame>
    <description>DCR is defined as the percentage of participants in the analysis population who have a CR, PR or stable disease per RECIST 1.1.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Small Cell Lung Carcinoma</condition>
  <arm_group>
    <arm_group_label>Camrelizumab+Irinotecan+Platinum→Camrelizumab+apatinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received intravenous infusions of Camrelizumab 200 mg in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) or Cisplatin 30 milligrams per square meter (mg/m^2) followed by Irinotecan 65 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4/5/6). On Days 8 of every 21-day cycle during the induction phase (Cycles 1-4/5/6), Cisplatin 30 mg/m^2 and Irinotecan 65 mg/m^2 was administered. Thereafter, participants received maintenance (Cycle onward) Camrelizumab 200 mg on Day 1 of every 21-day cycle with Apatinib 250mg until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Camrelizumab，an engineered anti-PD-1 antibody</intervention_name>
    <description>Camrelizumab intravenous infusion was administered at a dose of 200 mg on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4/5/6) and maintenance phase (Cycle onward).</description>
    <arm_group_label>Camrelizumab+Irinotecan+Platinum→Camrelizumab+apatinib</arm_group_label>
    <other_name>SHR-1210</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Platinum</intervention_name>
    <description>Carboplatin： Carboplatin intravenous infusion to achieve an initial target AUC of 5 mg/mL/min was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4/5/6).&#xD;
Cisplatin： Cisplatin intravenous infusion was administered at a dose of 30 milligrams per square meter (mg/m^2) on Day 1，8 of every 21-day cycle during the induction phase (Cycles 1-4/5/6).</description>
    <arm_group_label>Camrelizumab+Irinotecan+Platinum→Camrelizumab+apatinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Irinotecan</intervention_name>
    <description>Irinotecan intravenous infusion was administered at a dose of 65 milligrams per square meter (mg/m^2) on Day 1，8 of every 21-day cycle during the induction phase (Cycles 1-4/5/6).</description>
    <arm_group_label>Camrelizumab+Irinotecan+Platinum→Camrelizumab+apatinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib</intervention_name>
    <description>Apatinib was administered at a dose of 250 mg during the maintenance phase.</description>
    <arm_group_label>Camrelizumab+Irinotecan+Platinum→Camrelizumab+apatinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. Extensive small cell lung cancer diagnosed by pathology or cytology.&#xD;
&#xD;
          2. Patients with extensive stage small cell lung cancer who have not previously been&#xD;
             treated for tumors (including radiotherapy, chemotherapy, use of similar VEGFR&#xD;
             inhibitors and immune checkpoint inhibitors).&#xD;
&#xD;
          3. The disease progress of the patients with limited SCLC who had received&#xD;
             chemotherapy/radiotherapy before, and no further treatment more than 6 months after&#xD;
             the last chemotherapy/radiotherapy.&#xD;
&#xD;
          4. Expected survival≥3months.&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.&#xD;
&#xD;
          6. Subjects enrolled must have measurable lesion(s) according to the RECIST 1.1 standard&#xD;
             (the CT scan length of the tumor lesion &gt; 10 mm)&#xD;
&#xD;
          7. The main organ function is normal. All baseline laboratory requirements will be&#xD;
             assessed and should be obtained within -14 days of randomization. Screening laboratory&#xD;
             values must meet the following criteria. a .Hemoglobin ≥ 9.0 g/dL (90 g/L) b .Absolute&#xD;
             neutrophil count ≥ 1.5 x 109/L c .Platelets ≥ 100 x 109/L d .Total bilirubin (TBIL) ≤&#xD;
             1 x upper limit of normal (ULN) e .Alanine aminotransferase (ALT) and aspartate&#xD;
             aminotransferase (AST) ≤ 1.5 x upper limit of normal(ULN); alkaline phosphatase ≤ 5 x&#xD;
             ULN f .Serum creatinine ≤ 1.5 x ULN or creatinine clearance &gt; 45 mL/minute (using&#xD;
             Cockcroft/Gault formula)&#xD;
&#xD;
          8. Emale participants of childbearing potential must have a negative serum pregnancy test&#xD;
             within -7 days of randomization and must be willing to use very efficient barrier&#xD;
             methods of contraception or a barrier method plus a hormonal method starting with the&#xD;
             screening visit through 60 days (about 5 drug half-life + menstrual cycle) after the&#xD;
             last dose of SHR-1210. Male participants with a female partner(s) of child-bearing&#xD;
             potential must be willing to use very efficient barriermethods of contraception from&#xD;
             screening through 120 days (about 5 drug half-life + sperm depletion cycle) after the&#xD;
             last dose of SHR-1210.&#xD;
&#xD;
          9. Subjects should be voluntarily participate in clinical studies and informed consent&#xD;
             should be signed.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1.Imaging (CT or MRI) showed the presence of a central tumor that invades the local large&#xD;
        vessels. Or there are obvious pulmonary cavitation or necrotizing tumors. 2. Patients with&#xD;
        brain metastasis or meningeal metastasis.&#xD;
&#xD;
        3.Subjects used immunosuppressive drugs excluding nasal spray and inhaled corticosteroids&#xD;
        or systemic steroids at physiological doses(prednisolone≤10 mg/day or other corticosteroids&#xD;
        of the same pharmacophysiological dose) within 14 days before the first dose.&#xD;
&#xD;
        4.Uncontrollable hypertension (systolic blood pressure ≥140 mmHg or diastolic blood&#xD;
        pressure ≥90 mmHg, despite with the optimal medical treatment.&#xD;
&#xD;
        5.Subjects with grade II or above myocardial ischemia or myocardial infarction and poorly&#xD;
        controlled arrhythmias (QTc interval &gt; 450 ms for males and QTc interval &gt; 470 ms for&#xD;
        females). Subjects with grade III-IV cardiac insufficiency or with left ventricular&#xD;
        ejection fraction (LVEF) less than 50% had myocardial infarction within 6 months before&#xD;
        admission according to NYHA criteria.&#xD;
&#xD;
        6.Accompanied by uncontrolled pleural effusion, pericardial effusion, or ascites requiring&#xD;
        repeated drainage.&#xD;
&#xD;
        7.Participants who had any active autoimmune disease or a history of autoimmune disease&#xD;
        (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia,&#xD;
        uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis ,&#xD;
        Hyperthyroidism, decreased thyroid function).&#xD;
&#xD;
        8.Subjects with childhood asthma has completely resolved, adults can be included without&#xD;
        any intervention; subjects with bronchodilators for medical intervention can not be&#xD;
        included .&#xD;
&#xD;
        9.Participants who had abnormal blood coagulation (INR&gt;1.5 or PT&gt; ULN+4s, and or APTT &gt; 1.5&#xD;
        ULN), bleeding tendency or receiving thrombolytic or anticoagulation；Note: under the&#xD;
        premise that the international standardized ratio of prothrombin time (INR) is ≤ 1.5, the&#xD;
        use of low-dose heparin (60,000-12,000u per day for adults) or low-dose aspirin (≤ 100mg&#xD;
        per day) is allowed for preventive purposes.&#xD;
&#xD;
        10.Urine routine indicates urinary protein ≥ ++, or confirms that 24-hour urine protein is&#xD;
        ≥1.0 g.&#xD;
&#xD;
        11.Patients with non-healing wound, non-healing ulcer, or non-healing bone fracture; 12.The&#xD;
        patient has severe infection within 4 weeks before first administration（such as the need&#xD;
        for intravenous antibiotics, antifungals or antivirals) and unexplained fever within 7 days&#xD;
        before administration, ≥38.5 °.&#xD;
&#xD;
        13.There was significant coughing blood and significant clinically significant bleeding&#xD;
        symptoms or a clear tendency to hemorrhage in the first 2 months before enrollment (such as&#xD;
        gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal occult blood ++ and above at&#xD;
        baseline, or suffering from vasculitis, etc.).&#xD;
&#xD;
        14.Serious Arterial / venous thrombosis events, such as cerebrovascular accidents&#xD;
        (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein&#xD;
        thrombosis, and pulmonary embolism, within 12 months before enrollment.&#xD;
&#xD;
        15.Known history of testing positive for human immunodeficiency virus (HIV) or known&#xD;
        acquired immunodeficiency syndrome (AIDS).Positive test for hepatitis B virus surface&#xD;
        antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or&#xD;
        chronic infection. (HBV: HBsAg positive and HBV DNA ≥ 500 IU/mL ; HVC: HCV RNA positive and&#xD;
        abnormal liver function). And subjects with active tuberculosis.&#xD;
&#xD;
        16.Patients with a clear history of allergies may be potentially allergic to or intolerant&#xD;
        to biological agents such as irinotecan, cisplatin, apatinib, and carillizumab; 17.There&#xD;
        are obvious factors affecting oral drug absorption, such as inability to swallow, chronic&#xD;
        diarrhea and intestinal obstruction. Or sinus or perforation of empty organs within 6&#xD;
        months.&#xD;
&#xD;
        18.Any known mental illness or substance abuse that may have an impact on compliance with&#xD;
        the test requirements.&#xD;
&#xD;
        19.There are other factors lead to patients can not participate in this clinical study by&#xD;
        the judgment of the investigator.&#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_contact>
    <last_name>Li Zhang, Ph.D</last_name>
    <phone>+8613911339836</phone>
    <email>zhanglipumch@aliyun.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Beijing Union Medical College Hospital</name>
      <address>
        <city>Beijing</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Li Zhang, Ph.D</last_name>
      <phone>+8613911339836</phone>
      <email>zhanglipumch@aliyun.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 22, 2020</study_first_submitted>
  <study_first_submitted_qc>June 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>June 28, 2020</last_update_submitted>
  <last_update_submitted_qc>June 28, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 1, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Peking Union Medical College Hospital</investigator_affiliation>
    <investigator_full_name>Li Zhang</investigator_full_name>
    <investigator_title>professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Small Cell Lung Carcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Irinotecan</mesh_term>
    <mesh_term>Apatinib</mesh_term>
    <mesh_term>Antibodies</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT04453930
org study id: HS-2195
nct id: NCT04453930
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This single arm, open label, single center, prospective study was designed to evaluate the
      safety and efficacy of Sequential Therapy of Camrelizumab (humanized monoclonal antibody
      against Programmed death 1 [PD-1] ) in combination with Chemotherapy（Irinotecan plus
      Platinum）and with Apatinib (selective Vascular Endothelial Growth Factor Receptor 2(VEGFR-2)
      tyrosine kinase inhibitor [TKI]) in chemotherapy-naive participants with SCLC. Participants
      will receive Camrelizumab + Irinotecan + Platinum on 21-day cycles for 4-6 cycles in the
      induction phase followed by maintenance with Camrelizumab + Apatinib until progressive
      disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid
      Tumors Version 1.1 (RECIST v1.1). Treatment can be continued until persistent radiographic PD
      or symptomatic deterioration.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free Survival (PFS) as assessed by RECIST 1.1
time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years.
description: PFS is defined as the time from date of enrollment to the date of the first documentation of progressive disease (PD) or death from any cause, whichever occurs first per RECIST 1.1.
measure: Duration of Overall Survival (OS)
time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years.
description: OS is defined as the time from date of enrollment to date of death from any cause.
measure: Disease Control Rate (DCR) as assessed by RECIST 1.1
time frame: through study completion, an average of 2 year.
description: DCR is defined as the percentage of participants in the analysis population who have a CR, PR or stable disease per RECIST 1.1.
measure: Objective Response Rate (ORR) as assessed by RECIST 1.1
time frame: through study completion, an average of 2 year.
description: ORR is defined as the percentage of participants in the analysis population who have a Complete Response(CR) or a Partial Response(PR) per RECIST 1.1.
measure: Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1
time frame: through study completion, an average of 2 year.
description: DCR is defined as the percentage of participants in the analysis population who have a CR, PR or stable disease per RECIST 1.1.
arm group label: Camrelizumab+Irinotecan+Platinum→Camrelizumab+apatinib
arm group type: Experimental
description: Participants received intravenous infusions of Camrelizumab 200 mg in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) or Cisplatin 30 milligrams per square meter (mg/m^2) followed by Irinotecan 65 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4/5/6). On Days 8 of every 21-day cycle during the induction phase (Cycles 1-4/5/6), Cisplatin 30 mg/m^2 and Irinotecan 65 mg/m^2 was administered. Thereafter, participants received maintenance (Cycle onward) Camrelizumab 200 mg on Day 1 of every 21-day cycle with Apatinib 250mg until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
intervention type: Drug
intervention name: Camrelizumab，an engineered anti-PD-1 antibody
description: Camrelizumab intravenous infusion was administered at a dose of 200 mg on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4/5/6) and maintenance phase (Cycle onward).
arm group label: Camrelizumab+Irinotecan+Platinum→Camrelizumab+apatinib
other name: SHR-1210
intervention type: Drug
intervention name: Platinum
description: Carboplatin： Carboplatin intravenous infusion to achieve an initial target AUC of 5 mg/mL/min was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4/5/6).
Cisplatin： Cisplatin intravenous infusion was administered at a dose of 30 milligrams per square meter (mg/m^2) on Day 1，8 of every 21-day cycle during the induction phase (Cycles 1-4/5/6).
arm group label: Camrelizumab+Irinotecan+Platinum→Camrelizumab+apatinib
intervention type: Drug
intervention name: Irinotecan
description: Irinotecan intravenous infusion was administered at a dose of 65 milligrams per square meter (mg/m^2) on Day 1，8 of every 21-day cycle during the induction phase (Cycles 1-4/5/6).
arm group label: Camrelizumab+Irinotecan+Platinum→Camrelizumab+apatinib
intervention type: Drug
intervention name: Apatinib
description: Apatinib was administered at a dose of 250 mg during the maintenance phase.
arm group label: Camrelizumab+Irinotecan+Platinum→Camrelizumab+apatinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Li Zhang, Ph.D
phone: +8613911339836
email: zhanglipumch@aliyun.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Peking Union Medical College Hospital
investigator full name: Li Zhang
investigator title: professor
mesh term: Small Cell Lung Carcinoma
mesh term: Irinotecan
mesh term: Apatinib
mesh term: Antibodies
sharing ipd: No