<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/NCT04415385</url>
  </required_header>
  <id_info>
    <org_study_id>ChiECRCT20200088</org_study_id>
    <nct_id>NCT04415385</nct_id>
  </id_info>
  <brief_title>The Combination of Camrelizumab and Apatinib as Second-line Therapy for Advanced Pancreatic Carcinoma</brief_title>
  <official_title>The Combination of Camrelizumab and Apatinib as Second-line Therapy for Advanced Pancreatic Cancer Patients Who Failed Standard First-line Treatment: a Single Arm, Open-label, Phase 2 Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zhejiang Cancer Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zhejiang Cancer 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 is an single arm, open-label, phase II trial to evaluate safety and efficacy of using&#xD;
      the combination of Camrelizumab with apatinib as second-line therapy for advanced PDAC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PD-1 antibody Camrelizumab is a humanized monoclonal antibody, and the heavy chain is&#xD;
      immunoglobulin G4 (IgG4), the light chain is immunoglobulin κ (IgK). Camrelizumab&#xD;
      specifically binds to PD-1 and blocks the interaction of PD-1 with its ligand (PD-L1),&#xD;
      allowing T cells to recover against tumor immune responses.&#xD;
&#xD;
      Response rate, progression-free survival, overall survival, duration of response，disease&#xD;
      control rate, drugs related side effects were recorded and analyzed, to assess the&#xD;
      combination treatment could or couldn't benefit the patients with advanced pancreatic cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">June 1, 2020</start_date>
  <completion_date type="Anticipated">June 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2022</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>ORR</measure>
    <time_frame>Through study completion, an average of 2 years.</time_frame>
    <description>ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PFS</measure>
    <time_frame>Through study completion, an average of 2 years.</time_frame>
    <description>Progression-free survival is defined as the duration from date of enrollment to the first occurrence of progression of disease or death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OS</measure>
    <time_frame>Through study completion, an average of 2 years.</time_frame>
    <description>Overall survival is defined as the duration from date of enrollment to the date of death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DoR</measure>
    <time_frame>Through study completion, an average of 2 years.</time_frame>
    <description>DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DCR</measure>
    <time_frame>Through study completion, an average of 2 years.</time_frame>
    <description>DCR is defined as the percentage of participants in the analysis population who have a CR, PR or stable disease (SD) per RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Events (AEs) in the treatment of Camrelizumab in combination with apatinib</measure>
    <time_frame>Through study completion, an average of 2 years.</time_frame>
    <description>Number of participants with adverse events occurring up to 30 days after the last administration are evaluated and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">48</enrollment>
  <condition>Pancreatic Cancer</condition>
  <arm_group>
    <arm_group_label>Camrelizumab + Apatinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive Camrelizumab 200mg intravenously every 2 weeks and apatinib 250mg orally once daily until disease progression or unacceptable toxicity</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Camrelizumab</intervention_name>
    <description>200mg, intravenous infusion for 30 minutes (including the time of the tube, the overall infusion time is not shorter than 20 minutes, no longer than 60 minutes), once every 2 weeks.</description>
    <arm_group_label>Camrelizumab + Apatinib</arm_group_label>
    <other_name>SHR-1210</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib</intervention_name>
    <description>250 mg, orally once a day. Take about half an hour after a meal with warm water.</description>
    <arm_group_label>Camrelizumab + Apatinib</arm_group_label>
    <other_name>Apatinib Mesylate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects voluntarily joined the study and signed informed consent. Able to comply with&#xD;
             the required protocol and follow-up procedures;&#xD;
&#xD;
          2. Histologically or cytologically confirmed recurrent / metastatic advanced pancreatic&#xD;
             cancer, have received gemcitabine or nab-paclitaxel based standard chemotherapy;&#xD;
&#xD;
          3. Male and Female, Age ≥ 18 years and ≤ 70 years;&#xD;
&#xD;
          4. Life expectancy exceeds 3 months;&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2;&#xD;
&#xD;
          6. Patients must have measurable disease per RECIST 1.1;&#xD;
&#xD;
          7. Subjects with previous systemic therapy completed more than 2 weeks can be&#xD;
             enrolled,and the treatment-related AE should be restored to NCI-CTCAE v5.0 less than&#xD;
             grade 1 (except for grade 2 hair loss)&#xD;
&#xD;
          8. Subjects with asymptomatic central nervous system metastasis, or asymptomatic brain&#xD;
             metastases after treatment, need to be examined by CT or MRI, disease stable for at&#xD;
             least 3 months, and at least 4 weeks without steroid medication;&#xD;
&#xD;
          9. Subjects must provide tumor tissue and blood samples for specific index testing;&#xD;
&#xD;
         10. The HBsAg test is negative; if the HBsAg or HBcAb test is positive, the HBV DNA test&#xD;
             must be less than 1000 IU / ml;&#xD;
&#xD;
         11. The HCV-Ab test is negative; if the HCV-Ab or HCV-RNA test is positive, ALT and AST&#xD;
             CTCAE v5 ≤ 1 level and ≤ 3 × ULN; The joint infection of hepatitis B and C shouled be&#xD;
             excluded;&#xD;
&#xD;
         12. Subjects must have adequate organ function (without blood transfusion, without growth&#xD;
             factor or blood components support within 14 days before enrollment)as determined by:&#xD;
             Hemoglobin ≥ 9 g/dL; Absolute neutrophil count (ANC) ≥1.5×109/L; Platelet count ≥&#xD;
             90×109/L ; Total bilirubin ≤ 1×upper limit of normal(ULN)；alanine aminotransferase&#xD;
             (ALT) and aspartate aminotransferase (AST) ≤3×upper limit of normal(ULN), for subjects&#xD;
             with liver metastases, ALT and AST≤5×ULN; Alkaline phosphatase ≤ 2.5 × upper limit of&#xD;
             normal(ULN); urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 × upper limit of&#xD;
             normal(ULN);&#xD;
&#xD;
         13. Women of childbearing age should agree to use contraceptives (such as intrauterine&#xD;
             devices, contraceptives or condoms) during the study period and within 6 months of the&#xD;
             end of the study; the serum or urine pregnancy test is negative within 7 days prior to&#xD;
             study enrollment, and Must be non-lactating; males should agree to use contraceptives&#xD;
             during the study period and within 6 months of the end of the study period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. There is a third space effusion that cannot be controlled by drainage or other methods&#xD;
             (e.g., large amounts of pleural and ascites), and the efficacy of clinical treatment&#xD;
             cannot be evaluated;&#xD;
&#xD;
          2. Subjects who are ready to undergo or have previously undergone organ or bone marrow&#xD;
             transplantation;&#xD;
&#xD;
          3. Subjects with known active CNS metastases or cancerous meningitis；&#xD;
&#xD;
          4. Surgical and/or radiotherapy failed to radically treated spinal cord compression, or&#xD;
             previously diagnosed spinal cord compression did not have clinical evidence for&#xD;
             disease stable more than 1 week before the first administration；&#xD;
&#xD;
          5. Imaging examination showed that there was a clear manifestation of tumor invading the&#xD;
             abdominal great vessels；&#xD;
&#xD;
          6. Subjects with grade II or above myocardial ischemia, myocardial infarction, unstable&#xD;
             angina pectoris and uncontrolled arrhythmia within six months before the first&#xD;
             administration;&#xD;
&#xD;
          7. Subjects with grade III or IV cardiac insufficiency according to the New York Heart&#xD;
             Association (NYHA) criteria or color Doppler chocardiography showed left ventricular&#xD;
             ejection fraction (LVEF &lt; 50%) ;&#xD;
&#xD;
          8. Peripheral neuropathy with CTCAE V5 ≥ grade II;&#xD;
&#xD;
          9. Human immunodeficiency virus (HIV) infection;&#xD;
&#xD;
         10. Subjects have active pulmonary tuberculosis;&#xD;
&#xD;
         11. Previous or current interstitial pneumonia, pneumoconiosis, radiation pneumonia,&#xD;
             drug-related pneumonia, severe impairment of lung function, etc. may interfere with&#xD;
             the detection and management of suspected drug-related pulmonary toxicity；&#xD;
&#xD;
         12. Subjects had known active or suspected autoimmune disease.Enrollment was allowed to be&#xD;
             stable and did not require systemic immunosuppressive therapy；&#xD;
&#xD;
         13. Subjects received the vaccine within 28 days before the first use of the study drug；&#xD;
&#xD;
         14. Subjects requiring systemic corticosteroids (&gt;10 mg/day prednisone or equivalent doses&#xD;
             of the same drug) or other immunosuppressive therapy within 14 days before or during&#xD;
             the first dose of the study drug.Enrollment was allowed if inhaled or topical steroids&#xD;
             or adrenaline replacement therapy at a dose of &lt;10 mg/day prednisone were allowed in&#xD;
             the absence of active autoimmune disease；&#xD;
&#xD;
         15. Any active infection requiring systemic anti-infective treatment occurred within 14&#xD;
             days prior to the first administration of the study drug；&#xD;
&#xD;
         16. Radiotherapy, chemotherapy, surgical treatment or other targeted therapy for&#xD;
             pancreatic cancer had been received within 1 week before the first administration of&#xD;
             the study drug and had not progressed from previous treatment;&#xD;
&#xD;
         17. Major surgery was performed within 28 days before the first administration. The&#xD;
             definition of major surgery in this study is that recovery time of at least 3 weeks&#xD;
             after surgery is required to be able to accept the surgery treated in this study.Tumor&#xD;
             aspiration or lymph node biopsy allowed enrollment；&#xD;
&#xD;
         18. Subjects received radical radiotherapy within 3 months before the first administration&#xD;
             of the study drug;&#xD;
&#xD;
         19. Other anti tumor treatments may be received during the study interval.Such as&#xD;
             chemotherapy or radiotherapy (except palliative radiotherapy);&#xD;
&#xD;
         20. Subjects have previously received anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or&#xD;
             anti-CTLA-4 antibody treatment, or any other antibody or T cell co-stimulation drugs&#xD;
             or any drugs that target immune checkpoint;&#xD;
&#xD;
         21. Participating in other clinical studies or planning to start this study is less than&#xD;
             14 days from the end of treatment in a previous clinical study;&#xD;
&#xD;
         22. Severe allergy to any monoclonal antibody or study drug excipient;&#xD;
&#xD;
         23. Women who are pregnant or breastfeeding, those with fertility who are unwilling or&#xD;
             unable to take effective contraception;&#xD;
&#xD;
         24. Known history of psychotropic drug abuse or drug use. Subjects who have stopped&#xD;
             drinking can be enrolled；&#xD;
&#xD;
         25. The investigator judged that the subjects had other factors that could lead to the&#xD;
             forced termination of the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Wangxia Lv, Master</last_name>
    <phone>+8613757141026</phone>
    <email>lvwangxia@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Zhejiang Cancer Hospital</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wangxia Lv, Master</last_name>
      <phone>+8613757141026</phone>
      <email>lvwangxia@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>June 2, 2020</last_update_submitted>
  <last_update_submitted_qc>June 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 4, 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>Pancreatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apatinib</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/NCT04415385
org study id: ChiECRCT20200088
nct id: NCT04415385
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This is an single arm, open-label, phase II trial to evaluate safety and efficacy of using
      the combination of Camrelizumab with apatinib as second-line therapy for advanced PDAC.
PD-1 antibody Camrelizumab is a humanized monoclonal antibody, and the heavy chain is
      immunoglobulin G4 (IgG4), the light chain is immunoglobulin κ (IgK). Camrelizumab
      specifically binds to PD-1 and blocks the interaction of PD-1 with its ligand (PD-L1),
      allowing T cells to recover against tumor immune responses.

      Response rate, progression-free survival, overall survival, duration of response，disease
      control rate, drugs related side effects were recorded and analyzed, to assess the
      combination treatment could or couldn't benefit the patients with advanced pancreatic cancer.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: ORR
time frame: Through study completion, an average of 2 years.
description: ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
measure: PFS
time frame: Through study completion, an average of 2 years.
description: Progression-free survival is defined as the duration from date of enrollment to the first occurrence of progression of disease or death from any cause
measure: OS
time frame: Through study completion, an average of 2 years.
description: Overall survival is defined as the duration from date of enrollment to the date of death from any cause.
measure: DoR
time frame: Through study completion, an average of 2 years.
description: DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.
measure: DCR
time frame: Through study completion, an average of 2 years.
description: DCR is defined as the percentage of participants in the analysis population who have a CR, PR or stable disease (SD) per RECIST 1.1.
measure: Incidence of Adverse Events (AEs) in the treatment of Camrelizumab in combination with apatinib
time frame: Through study completion, an average of 2 years.
description: Number of participants with adverse events occurring up to 30 days after the last administration are evaluated and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0
arm group label: Camrelizumab + Apatinib
arm group type: Experimental
description: Participants receive Camrelizumab 200mg intravenously every 2 weeks and apatinib 250mg orally once daily until disease progression or unacceptable toxicity
intervention type: Drug
intervention name: Camrelizumab
description: 200mg, intravenous infusion for 30 minutes (including the time of the tube, the overall infusion time is not shorter than 20 minutes, no longer than 60 minutes), once every 2 weeks.
arm group label: Camrelizumab + Apatinib
other name: SHR-1210
intervention type: Drug
intervention name: Apatinib
description: 250 mg, orally once a day. Take about half an hour after a meal with warm water.
arm group label: Camrelizumab + Apatinib
other name: Apatinib Mesylate
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Wangxia Lv, Master
phone: +8613757141026
email: lvwangxia@163.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Pancreatic Neoplasms
mesh term: Apatinib
sharing ipd: No