<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/NCT04425135</url>
  </required_header>
  <id_info>
    <org_study_id>OBU-ALKNSCLC-IIT-SHR1210-APA-C</org_study_id>
    <nct_id>NCT04425135</nct_id>
  </id_info>
  <brief_title>Camrelizumab Combined With Apatinib Mesylate and Standard Chemotherapy (Pemetrixed + Carboplatin) in Patients With Tyrosine Kinase Inhibitor Failure in ALK-positive Advanced NSCLC</brief_title>
  <official_title>Phase II Single-arm Clinical Study of Camrelizumab Combined With Apatinib Mesylate and Standard Chemotherapy (Pemetrixed +Carboplatin) in Patients With Tyrosine Kinase Inhibitor Failure in ALK-positive Advanced NSCLC</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The First Affiliated Hospital of Xiamen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The First Affiliated Hospital of Xiamen 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 a phase II single-arm clinical study.The purpose of this study was to evaluate&#xD;
      the efficacy and safety of carrelizumab combined with apatinib mesylate and standard&#xD;
      chemotherapy (pemetrexed plus carboplatin) in patients with advanced non-squamous and&#xD;
      non-small cell lung cancer who have failed tyrosine kinase inhibitor therapy and are&#xD;
      ALK-positive.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">July 2020</start_date>
  <completion_date type="Anticipated">January 2025</completion_date>
  <primary_completion_date type="Anticipated">January 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>Objective response rate (ORR)</measure>
    <time_frame>up to approximately 1 year</time_frame>
    <description>ORR, determined using RECIST v1.1, defined as best overall response (CR or PR) across all assessment time points during the period from enrolment to termination of trial treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS)</measure>
    <time_frame>up to approximately 1 year</time_frame>
    <description>PFS, defined as the time from treatment to the first occurrence of disease progression as determined by the investigator with use of RECIST v1.1 or death from any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>up to approximately 1 year</time_frame>
    <description>Determined using RECIST v1.1 criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival Rate at 1-year (OSR)</measure>
    <time_frame>up to approximately 1 year</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">59</enrollment>
  <condition>Lung Neoplasms</condition>
  <arm_group>
    <arm_group_label>Camrelizumab +apatinib mesylate+Pemetrixed + Carboplatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Camrelizumab combined with apatinib mesylate,Pemetrixed and Carboplatin in the treatment（4-6 cycle）of effective (CR, PR, SD) patients continued to be treated with Camrelizumab combined with apadine mesylate until PD, toxicity intolerance, and other reasons that the researcher thinks need to stop the research treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Camrelizumab</intervention_name>
    <description>200mg,D1,ivgtt, Q3w.</description>
    <arm_group_label>Camrelizumab +apatinib mesylate+Pemetrixed + Carboplatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib</intervention_name>
    <description>250mg,Qd,Q3W.</description>
    <arm_group_label>Camrelizumab +apatinib mesylate+Pemetrixed + Carboplatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pemetrixed</intervention_name>
    <description>500 mg/m2,D1,ivgtt, Q3w.</description>
    <arm_group_label>Camrelizumab +apatinib mesylate+Pemetrixed + Carboplatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>AUC=5~6,D1,ivgtt, Q3w.</description>
    <arm_group_label>Camrelizumab +apatinib mesylate+Pemetrixed + Carboplatin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 - 75 year，male or female；&#xD;
&#xD;
          -  Subjects with histologically or cytologically confirmed advanced non-squamous&#xD;
             non-small cell lung cancer, imaging stage IIIb~IV；&#xD;
&#xD;
          -  ALK fusion gene is positive and meets the following conditions:&#xD;
&#xD;
               1. First-line treatment failure after previous second-generation ALK-TKI (including&#xD;
                  but not limited to Aletinib, Ceritinib, Brigatinib, and x-396);&#xD;
&#xD;
               2. Previous first-generation AlK-TKI (crizotinib) and second-generation ALK-TKI&#xD;
                  (including but not limited to Aletinib, Ceritinib, Brigatinib, and x-396) failed.&#xD;
&#xD;
          -  Patients with at least one evaluable or measurable lesions as per RECIST version 1.1；&#xD;
&#xD;
          -  Patients who have not previously received systematic chemotherapy for advanced lung&#xD;
             cancer .Can also be enrolled if you have previously received Neoadjuvant or adjuvant&#xD;
             therapy；&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1；&#xD;
&#xD;
          -  Survival expectation ≥ 3 months;&#xD;
&#xD;
          -  Women of childbearing age must have a serum pregnancy study within 2 weeks prior to&#xD;
             the first dose and the results are negative. Female subjects of childbearing age and&#xD;
             partners who are women of childbearing age must be contraceptive during the study&#xD;
             period and within 180 days after the last administration of the study drug;&#xD;
&#xD;
          -  The laboratory test value of the patient before medication should meet the following&#xD;
             standards:&#xD;
&#xD;
               1. Routine blood：WBC≥3.0 × 109/L；ANC≥1.5 × 109/L；PLT≥90 × 109/L；HGB≥9.0 g/dL；&#xD;
&#xD;
               2. Liver function：TBIL≤1.5 × ULN，AST≤2.5 × ULN，ALT≤2.5 × ULN（Subjects with liver&#xD;
                  metastasis，AST≤5× ULN，ALT≤5 × ULN）；&#xD;
&#xD;
               3. Renal function：Cr≤1.5 × ULN or CrCl ≥50 mL/min；&#xD;
&#xD;
               4. Blood coagulation function：INR≤1.5，APTT≤1.5 ×ULN ；&#xD;
&#xD;
          -  Subjects voluntarily joined the study, signed informed consent, good compliance, and&#xD;
             followed up;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Tumor histology or cytology pathology confirmed that the components of small cell lung&#xD;
             cancer or squamous cell carcinoma were more than 10%；&#xD;
&#xD;
          -  Previously received any T cell costimulation or immunological checkpoint treatment,&#xD;
             including but not limited to CTLA-4 inhibitors, PD-1 inhibitors, PD-L1/2 inhibitors or&#xD;
             other T cell-targeting drugs；&#xD;
&#xD;
          -  An active autoimmune disease requiring systemic treatment (such as the use of&#xD;
             disease-alleviating drugs, corticosteroids or immunosuppressants) occurred within 2&#xD;
             years prior to the first administration.Alternative therapies (such as thyroxine,&#xD;
             insulin or physiological corticosteroids for adrenal or pituitary insufficiency) are&#xD;
             not considered systemic;&#xD;
&#xD;
          -  Interstitial lung disease, drug-induced pneumonia, radiation pneumonitis requiring&#xD;
             steroid therapy or active pneumonia with clinical symptoms or severe pulmonary&#xD;
             dysfunction；&#xD;
&#xD;
          -  Previous or current history of cancer other than NSCLC, except for non-melanoma skin&#xD;
             cancer, in-situ cervical cancer or other cancers that have received curable treatment&#xD;
             and have shown no signs of recurrence for at least 5 years；&#xD;
&#xD;
          -  Has not fully recovered from toxicity and/or complications from any intervention prior&#xD;
             to initiation of treatment (i.e., ≤ grade 1 or level required at baseline, excluding&#xD;
             fatigue or hair loss);&#xD;
&#xD;
          -  Have a tendency to hereditary bleeding or coagulopathy. Clinically significant&#xD;
             bleeding symptoms or clear bleeding tendency within 3 months prior to enrollment, such&#xD;
             as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood++&#xD;
             and above；&#xD;
&#xD;
          -  Patients with clear or suspected brain metastases. Patients with a history of brain&#xD;
             metastases （must be completed and patients who are no longer in need of corticosteroid&#xD;
             therapy） can be enrolled; for patients with asymptomatic, lesions ≤ 3 and single less&#xD;
             than 10 mm, who is determined by the investigator whether or not to enroll ;&#xD;
&#xD;
          -  There are clinical symptoms or diseases of the heart that are not well controlled,&#xD;
             such as: (1) heart failure of NYHA class 2 or higher (2) unstable angina (3)&#xD;
             myocardial infarction within 24 weeks (4) clinical need for treatment or&#xD;
             Interventional supraventricular or ventricular arrhythmia；&#xD;
&#xD;
          -  Uncontrolled hypertension after treatment (systolic blood pressure &gt; 140 mmHg and/or&#xD;
             diastolic blood pressure &gt; 90mmHg), with a history of hypertensive crisis or&#xD;
             hypertensive encephalopathy;Uncontrolled hyperglycemia after treatment (fasting&#xD;
             glucose &gt;8.9mmol/L);&#xD;
&#xD;
          -  There is a clinically uncontrollable third interstitial fluid (such as pleural&#xD;
             effusion/pericardial effusion, patients who do not need drainage or stop drainage for&#xD;
             3 days without significant increase in effusion can be enrolled)；&#xD;
&#xD;
          -  Imaging (CT or MRI) shows that the tumor invades the large blood vessels or the&#xD;
             investigator judges that the tumor is highly likely to invade the important blood&#xD;
             vessels during the follow-up study and cause fatal bleeding.&#xD;
&#xD;
          -  Have a history of immunodeficiency, including HIV positive, or other acquired,&#xD;
             congenital immunodeficiency disease, or history of organ transplantation and bone&#xD;
             marrow transplantation；&#xD;
&#xD;
          -  Active hepatitis B (positive detection of hepatitis B virus surface antigen [HBsAg] in&#xD;
             the screening period, and detection of HBV-DNA detection value higher than the upper&#xD;
             limit of the normal value of the laboratory in the research center) or hepatitis C (in&#xD;
             the screening period, hepatitis C virus surface antibody [ HCsAb] positive, HCV-RNA&#xD;
             positive)；&#xD;
&#xD;
          -  Subjects who have received or will receive live vaccine within 30 days of the first&#xD;
             treatment；&#xD;
&#xD;
          -  Subjects who simultaneously applied NMPA standard modern Traditional Chinese medicine&#xD;
             preparation against lung cancer and immunomodulator;&#xD;
&#xD;
          -  Allergic reactions to test drugs for this application；&#xD;
&#xD;
          -  The investigator determined that the subject had other factors that might lead to the&#xD;
             termination of the study.&#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>Jingxun Wu, doctor</last_name>
    <phone>15160085395</phone>
    <email>Jingxun_wu@163.com</email>
  </overall_contact>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>June 8, 2020</last_update_submitted>
  <last_update_submitted_qc>June 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 11, 2020</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>Lung Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Apatinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04425135
org study id: OBU-ALKNSCLC-IIT-SHR1210-APA-C
nct id: NCT04425135
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study is a phase II single-arm clinical study.The purpose of this study was to evaluate
      the efficacy and safety of carrelizumab combined with apatinib mesylate and standard
      chemotherapy (pemetrexed plus carboplatin) in patients with advanced non-squamous and
      non-small cell lung cancer who have failed tyrosine kinase inhibitor therapy and are
      ALK-positive.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate (ORR)
time frame: up to approximately 1 year
description: ORR, determined using RECIST v1.1, defined as best overall response (CR or PR) across all assessment time points during the period from enrolment to termination of trial treatment.
measure: Progression-Free Survival (PFS)
time frame: up to approximately 1 year
description: PFS, defined as the time from treatment to the first occurrence of disease progression as determined by the investigator with use of RECIST v1.1 or death from any cause, whichever occurs first.
measure: Disease Control Rate (DCR)
time frame: up to approximately 1 year
description: Determined using RECIST v1.1 criteria
measure: Overall Survival Rate at 1-year (OSR)
time frame: up to approximately 1 year
arm group label: Camrelizumab +apatinib mesylate+Pemetrixed + Carboplatin
arm group type: Experimental
description: Camrelizumab combined with apatinib mesylate,Pemetrixed and Carboplatin in the treatment（4-6 cycle）of effective (CR, PR, SD) patients continued to be treated with Camrelizumab combined with apadine mesylate until PD, toxicity intolerance, and other reasons that the researcher thinks need to stop the research treatment.
intervention type: Drug
intervention name: Camrelizumab
description: 200mg,D1,ivgtt, Q3w.
arm group label: Camrelizumab +apatinib mesylate+Pemetrixed + Carboplatin
intervention type: Drug
intervention name: Apatinib
description: 250mg,Qd,Q3W.
arm group label: Camrelizumab +apatinib mesylate+Pemetrixed + Carboplatin
intervention type: Drug
intervention name: Pemetrixed
description: 500 mg/m2,D1,ivgtt, Q3w.
arm group label: Camrelizumab +apatinib mesylate+Pemetrixed + Carboplatin
intervention type: Drug
intervention name: Carboplatin
description: AUC=5~6,D1,ivgtt, Q3w.
arm group label: Camrelizumab +apatinib mesylate+Pemetrixed + Carboplatin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Jingxun Wu, doctor
phone: 15160085395
email: Jingxun_wu@163.com
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carboplatin
mesh term: Apatinib
sharing ipd: Undecided