<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/NCT04425187</url>
  </required_header>
  <id_info>
    <org_study_id>BEVA-FLFX-001</org_study_id>
    <nct_id>NCT04425187</nct_id>
  </id_info>
  <brief_title>Bevacizumab Combined With Gefitinib in the Treatment of Advanced NSCLC</brief_title>
  <official_title>Bevacizumab Combined With Gefitinib in the Treatment of Advanced NSCLC Clinical Study of L858R Positive Mutation Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fudan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fudan University</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>
      To compare the efficacy and safety of gefitinib combined with bevacizumab and gefitinib in&#xD;
      the treatment of L858R positive mutation in exon 21 of EGFR gene in advanced NSCLC.&#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">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel 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>From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months</time_frame>
    <description>The PFS of gefitinib combined with bevacizumab and gefitinib alone were compared in patients with L858R mutation in exon 21 of EGFR gene in stage IIIB-IV local advanced, recurrent or metastatic NSCLC.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>PFS</condition>
  <arm_group>
    <arm_group_label>gefitinib</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>gefitinib&amp;bevacizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gefitinib</intervention_name>
    <description>gefitinib 250mg (1 tablet), once a day，PO</description>
    <arm_group_label>gefitinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bevacizumab Combined With Gefitinib</intervention_name>
    <description>Bevacizumab Combined With Gefitinib</description>
    <arm_group_label>gefitinib&amp;bevacizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 years old, gender unlimited.&#xD;
&#xD;
          2. NSCLC was confirmed by histology or cytology, and it was evaluated as stage IIIB-IV&#xD;
             local advanced, recurrent or metastatic patients who could not be treated surgically.&#xD;
             Note: ① the diagnosis result of NSCLC based on sputum cytology needs to be confirmed&#xD;
             by immunohistochemistry; ② the current disease should be treated by radiotherapy as&#xD;
             the first choice The subjects whose treatment strategy or follow-up target focus&#xD;
             judged by the researchers should take radiotherapy as the first treatment strategy&#xD;
             should not be selected.&#xD;
&#xD;
          3. No systemic anti-tumor therapy was received for locally advanced, recurrent or&#xD;
             metastatic NSCLC.&#xD;
&#xD;
          4. According to the method of second-generation sequencing, L858R point mutation in exon&#xD;
             21 of EGFR gene was found in primary NSCLC with or without any other coexisting&#xD;
             mutations.&#xD;
&#xD;
          5. Within 28 days before randomization, at least one measurable lesion was selected&#xD;
             according to the RECIST v1.1 standard (see Appendix 1); for the lesions that had&#xD;
             previously received radiotherapy, only when there was clear disease progression 3&#xD;
             months after the end of radiotherapy, can they be selected as target lesions.&#xD;
&#xD;
          6. ECoG general condition score is 0-1 (see Appendix 2).&#xD;
&#xD;
          7. Expected survival ≥ 12 weeks.&#xD;
&#xD;
          8. Patients receiving radiotherapy can be included in the group if they meet the&#xD;
             following conditions:&#xD;
&#xD;
             There was no history of lung disease radiotherapy within 28 days before randomization;&#xD;
             L. for radiotherapy outside the chest area, the interval from the end of final&#xD;
             radiotherapy to at least 28 days before randomization, and all toxic reactions have&#xD;
             recovered.&#xD;
&#xD;
          9. Good blood function within 14 days before randomization:&#xD;
&#xD;
        L. the absolute neutrophil count (ANC) was ≥ 1.5 × 109 / L (without the support of&#xD;
        granulocyte colony stimulating factor) and; L lymphocyte count ≥ 0.5 × 109 / L and; 1.&#xD;
        Platelet count ≥ 100 × 109 / L and; Hemoglobin ≥ 9 g / dl (in order to reach this standard,&#xD;
        patients can receive blood transfusion).&#xD;
&#xD;
        10. Good liver function within 14 days before randomization: L) total bilirubin ≤ 1.5 ×&#xD;
        upper normal limit (ULN) and;&#xD;
&#xD;
        1. Ast, ALT and ALP of patients without liver metastasis were less than 2.5 × ULN; ast, ALT&#xD;
        and ALP of patients with liver metastasis were less than 5 × ULN.&#xD;
&#xD;
        11. Good renal function within 14 days before randomization:&#xD;
&#xD;
        1. Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance ≥ 45 ml / min and; The&#xD;
        urine test paper of urine protein was less than 2 +. If the baseline urine analysis of&#xD;
        proteinuria patients is ≥ 2 +, 24-hour urine sample collection must be completed, and&#xD;
        24-hour urine protein ≤ 1 g; serum albumin ≥ 25 g / L.&#xD;
&#xD;
        12. Within 14 days before randomization, INR ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN. 13. Heart&#xD;
        function meets the requirement of left ventricular ejection fraction (LVEF) ≥ 50%.&#xD;
&#xD;
        14. Fertile women: during the treatment period and within 6 months after the last&#xD;
        administration, they agreed to abstinence (no heterosexual sexual intercourse) or use&#xD;
        contraceptive methods (contraceptive methods with a failure rate of less than 1%). If a&#xD;
        postmenopausal woman has not reached the postmenopausal state (menopausal time ≥ 12 months,&#xD;
        no other reason except menopause) and has not undergone sterilization (removal of ovaries&#xD;
        and / or uterus), she is defined as a woman with fertility.&#xD;
&#xD;
        15. Male: for male patients with fertility of female partners or pregnancy of female&#xD;
        partners, they agree to abstinence (no heterosexual sexual intercourse) or use condoms&#xD;
        within 6 months after the last administration, and agree not to donate sperm.&#xD;
&#xD;
        16. Sign the informed consent voluntarily. 17. The researchers judged that they could&#xD;
        comply with the research plan.&#xD;
&#xD;
        -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Histology or cytology confirmed mixed adenocarcinoma with squamous cells as the main&#xD;
             component (the proportion of squamous cells ≥ 10%).&#xD;
&#xD;
          2. There was a history of malignancy (except NSCLC) in the first 5 years before&#xD;
             randomization, except for malignancies with negligible risk of metastasis or death&#xD;
             (e.g., 5-year OS rate &gt; 90%), such as cervical carcinoma in situ, non melanoma skin&#xD;
             cancer, localized prostate cancer, ductal carcinoma in situ or stage I uterine cancer,&#xD;
             which were treated appropriately.&#xD;
&#xD;
          3. Previous hypertensive crisis, hypertensive encephalopathy, or uncontrolled&#xD;
             hypertension (blood pressure: systolic pressure &gt; 150 mmHg and / or diastolic pressure&#xD;
             &gt; 100 mmHg).&#xD;
&#xD;
          4. The tumor invades the main blood vessels. Researchers or local radiologists must rule&#xD;
             out evidence that the tumor is completely adjacent to, surrounding, or extending into&#xD;
             the lumen of a major artery, such as the pulmonary artery or superior vena cava.&#xD;
&#xD;
          5. Any other disease, neurological or metabolic dysfunction; medical examination or&#xD;
             laboratory finding that a disease or condition is suspected, which prohibits the use&#xD;
             of the test drug or exposes the patient to a high risk of treatment-related&#xD;
             complications.&#xD;
&#xD;
          6. It is highly suspected that there are patients with idiopathic pulmonary fibrosis,&#xD;
             organic pneumonia, drug-related pneumonia, idiopathic pneumonia, active pneumonia or&#xD;
             active tuberculosis.&#xD;
&#xD;
          7. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated&#xD;
             drainage (once a month or more frequently) allows patients to retain catheters.&#xD;
&#xD;
          8. History of hereditary bleeding constitution or coagulation disorder or other evidence&#xD;
             of increased bleeding risk.&#xD;
&#xD;
          9. There are non healing wounds, active ulcers or fractures.&#xD;
&#xD;
         10. Patients with tracheoesophageal fistula, gastrointestinal perforation or&#xD;
             gastrointestinal fistula, and intraperitoneal abscess in the first 6 months were&#xD;
             randomly assigned.&#xD;
&#xD;
         11. Cardiovascular diseases with clinical significance (such as active), including but not&#xD;
             limited to TIA (within 6 months before screening), myocardial infarction (within 6&#xD;
             months before screening), unstable angina, congestive heart failure with New York&#xD;
             Heart Association classification ≥ level II (see Appendix 3), and serious arrhythmias&#xD;
             beyond the control of drugs.&#xD;
&#xD;
         12. Within 3 months before randomization, there was a history of hemoptysis ≥ 2 levels,&#xD;
             that is, the blood volume of each bleeding event was &gt; 2.5ml.&#xD;
&#xD;
         13. Evidence of central nervous system metastasis, except for patients without any&#xD;
             symptoms or patients with symptoms but stable condition, at least 28 days after&#xD;
             treatment of central nervous system metastasis.&#xD;
&#xD;
         14. Major surgery (including open biopsy) or severe trauma was performed within 28 days&#xD;
             prior to randomization, or was expected to be performed during study treatment.&#xD;
&#xD;
        Severe infections occurring within 28 days prior to randomization, including but not&#xD;
        limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.&#xD;
&#xD;
        16 aspirin (325 mg / day) or other non steroidal anti-inflammatory drugs known to inhibit&#xD;
        platelet function are currently or recently used (within 10 days before bevacizumab was&#xD;
        first used).&#xD;
&#xD;
        17 full dose oral or parenteral anticoagulants or thrombolytic agents are currently or&#xD;
        recently used (within 10 days prior to the first use of bevacizumab). Preventive use of&#xD;
        anticoagulants is permitted.&#xD;
&#xD;
        18. Core biopsies or other minor operations were performed within 7 days prior to&#xD;
        randomization, but vascular access devices were not included. Vascular access devices&#xD;
        should be placed at least 2 days before the start of study treatment.&#xD;
&#xD;
        19. Those who are known to be allergic to bevacizumab, gefitinib and their excipients, or&#xD;
        to Chinese hamster ovarian cell products or other recombinant human or humanized&#xD;
        antibodies.&#xD;
&#xD;
        20. Those who were confirmed to be HCV positive, HIV positive, syphilis positive, or HBsAg&#xD;
        positive during the screening period, and whose HBV DNA titer in the peripheral blood was ≥&#xD;
        1000 copies / L.&#xD;
&#xD;
        21. Pregnancy or lactation, or pregnancy planning during the study. 22. Those who&#xD;
        participated in any other clinical trial and took the trial drug treatment within 30 days&#xD;
        before randomization.&#xD;
&#xD;
        23. The investigator determined that the risk of the subject was greater than any other&#xD;
        benefit.&#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_contact>
    <last_name>wang jia lei, doctor</last_name>
    <phone>18017312369</phone>
    <email>haitunqiao@hotmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Cancer hospital Fudan University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>wang jia lei, PD</last_name>
      <phone>18017312689</phone>
      <email>haitunqiao@hotmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>June 10, 2020</last_update_submitted>
  <last_update_submitted_qc>June 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fudan University</investigator_affiliation>
    <investigator_full_name>Jialei Wang</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bevacizumab</mesh_term>
    <mesh_term>Gefitinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</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/NCT04425187
org study id: BEVA-FLFX-001
nct id: NCT04425187
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
To compare the efficacy and safety of gefitinib combined with bevacizumab and gefitinib in
      the treatment of L858R positive mutation in exon 21 of EGFR gene in advanced NSCLC.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free survival (PFS)
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 18 months
description: The PFS of gefitinib combined with bevacizumab and gefitinib alone were compared in patients with L858R mutation in exon 21 of EGFR gene in stage IIIB-IV local advanced, recurrent or metastatic NSCLC.
arm group label: gefitinib
arm group type: Active Comparator
arm group label: gefitinib&bevacizumab
arm group type: Experimental
intervention type: Drug
intervention name: Gefitinib
description: gefitinib 250mg (1 tablet), once a day，PO
arm group label: gefitinib
intervention type: Drug
intervention name: Bevacizumab Combined With Gefitinib
description: Bevacizumab Combined With Gefitinib
arm group label: gefitinib&bevacizumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: wang jia lei, doctor
phone: 18017312369
email: haitunqiao@hotmail.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Fudan University
investigator full name: Jialei Wang
investigator title: Principal Investigator
mesh term: Bevacizumab
mesh term: Gefitinib
sharing ipd: Yes