<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/NCT03240549</url>
  </required_header>
  <id_info>
    <org_study_id>121-2016007</org_study_id>
    <nct_id>NCT03240549</nct_id>
  </id_info>
  <brief_title>Effectiveness and Safety of Adding Bevacizumab to First Line Chemotherapy in Lung Cancer Patients With Stable Disease</brief_title>
  <official_title>Effectiveness and Safety of Adding Bevacizumab to Chemotherapy in Patients With Advanced Lung Adenocarcinoma With Stable Disease After 2 Cycles of First Line Combination Chemotherapy: a Multicenter, Prospective Cohort Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beijing Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Beijing Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Previous studies have shown that the addition of bevacizumab to the standard first-line&#xD;
      platinum-based combination therapy can improve the objective response rate of patients with&#xD;
      advanced non-squamous non-small cell lung cancer by 20% to 28% and improve survival. Data&#xD;
      from these published literatures suggest that the improvement in objective response rates is&#xD;
      due mainly to patients with stable disease of chemotherapy. It has been reported that 15% of&#xD;
      patients achieved objective remission after continuing treatment with the regimen after&#xD;
      receiving 2 cycles of platinum-based combination chemotherapy. Therefore, the use of 2 cycles&#xD;
      of chemotherapy after stabilization of patients with bevacizumab, hoping to improve the&#xD;
      objective response rate of such patients 20%, and may improve survival. For the above&#xD;
      reasons, design this study to validate our hypothesis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Previous studies have shown that the addition of bevacizumab to the standard first-line&#xD;
      platinum-based combination therapy can improve the objective response rate of patients with&#xD;
      advanced non-squamous non-small cell lung cancer by 20% to 28% and improve survival. Data&#xD;
      from these published literatures suggest that the improvement in objective response rates is&#xD;
      due mainly to patients with stable disease of chemotherapy. It has been reported that 15% of&#xD;
      patients achieved objective remission after continuing treatment with the regimen after&#xD;
      receiving 2 cycles of platinum-based combination chemotherapy. Therefore, the use of 2 cycles&#xD;
      of chemotherapy after stabilization of patients with bevacizumab, hoping to improve the&#xD;
      objective response rate of such patients 20%, and may improve survival. For the above&#xD;
      reasons, design this study to validate our hypothesis.&#xD;
&#xD;
      So a prospective cohort study has been designed to confirm this hypothesis, patients with&#xD;
      advanced pulmonary adenocarcinoma who are stable after two cycles of platinum-based&#xD;
      combination chemotherapy are objects of this study, and they can choose to continue the&#xD;
      previous treatment regimen according to the guideline or adding bevacizumab to the regimen&#xD;
      independently until the progression or intolerance of toxicity, or 4 to 6 cycles of&#xD;
      chemotherapy in stable disease. The objective response rate in these two groups who received&#xD;
      different treatment is the primary endpoint and the toxicity, quality of life, the&#xD;
      progression free survival are the second endpoints.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">August 2017</start_date>
  <completion_date type="Anticipated">September 30, 2019</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2018</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>Factorial Assignment</intervention_model>
    <intervention_model_description>Prospective cohort study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective Response Rate</measure>
    <time_frame>Assessment of the response should be done from the written consent to the 3 month after the last patient inrolled in the study, assessed up to 24 months.</time_frame>
    <description>The percentage of patients who was assessed as complete response and partial response according RECIST (Response Evaluation In Solid Tumors).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of Response Duration of Response</measure>
    <time_frame>The start point was the first remission until the date of first documented progression or date of death from any cause, which came first, assessed up to 30 months.</time_frame>
    <description>The duration in responsive patients from the first remission to the progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival.</measure>
    <time_frame>The progression free survival was start from the written consent to the date of first documented progression or date of death from any cause, which came first,assessed up to 30 months.</time_frame>
    <description>The time from the day written consent to the first date of objective progression or death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Effects.</measure>
    <time_frame>Assessment should be done from the written consent to the date 28 days after the last chemotherapy, assessed up to 24 months.</time_frame>
    <description>The adverse effects of the treatment especially in hematology,cardiovascular system and renal system according the CTCAE 4.0, and the SAE(serious adverse events) in the treatment and follow up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life.</measure>
    <time_frame>Assessment should be done from the written consent to the finish of this study, assessed up to 36 months.</time_frame>
    <description>The quality of life should be assessed in the study using FACT-L(Functional Assessment of Cancer Therapy - Lung).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">159</enrollment>
  <condition>Non-small Cell Lung Cancer Metastatic</condition>
  <arm_group>
    <arm_group_label>conventional therapy group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Treatment with previous regimen of combined chemotherapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>bevacizumab group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Adding bevacizumab to the previous regimen of combined chemotherapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>bevacizumab</intervention_name>
    <description>The patients in conventional group continued the previous chemotherapy,and the patients in experimental group received adding bevacizumab to previous chemotherapy regimen.</description>
    <arm_group_label>bevacizumab group</arm_group_label>
    <other_name>avastin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent;&#xD;
&#xD;
          2. Age ≥18 years old, ≤75 years old;&#xD;
&#xD;
          3. Histologically or cytologically confirmed lung adenocarcinoma that can not treated&#xD;
             with surgery with locally advanced (stage IIIb) or metastatic (IV) disease. Do not&#xD;
             accept the diagnosis of lung adenocarcinoma alone based on sputum cytology;&#xD;
&#xD;
          4. Patients who have undergone targeted therapy for stage of disease (stage III, stage&#xD;
             IV, stage IV) have not received treatment for advanced disease chemotherapy for&#xD;
             patients with mutations associated with driving genes (eg, EGFR(epidermal growth&#xD;
             factor receptor) mutations, ALK(anaplastic lymphoma kinase) gene fusion, etc.) could&#xD;
             be included;&#xD;
&#xD;
          5. Patients who have received adjuvant or neoadjuvant therapy for non-metastatic lesions&#xD;
             can be enrolled for more than 12 months at the beginning of the study treatment;&#xD;
&#xD;
          6. Patients who have measurable lesions according to RECIST 1.1;&#xD;
&#xD;
          7. First line chemotherapy is platinum combined with pemetrexed or paclitaxel;&#xD;
&#xD;
          8. Stable disease after 2 cycles chemotherapy;&#xD;
&#xD;
          9. Eastern Cooperative Oncology Group performance Status of 0 or 1;&#xD;
&#xD;
         10. Life expectancy ≥12 weeks;&#xD;
&#xD;
         11. There was no dose adjustment due to toxicity during the previous 2 cycles of&#xD;
             combination chemotherapy;&#xD;
&#xD;
         12. The time delay is not more than 2 weeks due to toxicity of previous chemotherapy;&#xD;
&#xD;
         13. Adequate hematological function:ANC≥1.5 x 109/L，PLT≥100 x 109/L，Hb≥9 g/dL；&#xD;
&#xD;
         14. Adequate liver function:&#xD;
&#xD;
               -  Total bilirubin &lt;1.5x ULN(the upper limit of the normal value), and&#xD;
&#xD;
               -  for patients without liver metastases, aspartate aminotransferase (AST) and&#xD;
                  alanine aminotransferase (ALT) less than 2.5 times ULN; for patients with liver&#xD;
                  metastases, both were less than 5 times ULN;&#xD;
&#xD;
         15. Adequate renal function:&#xD;
&#xD;
             serum creatinine is equal to or less than 1.5 times ULN (upper limit of normal), - or&#xD;
             creatinine clearance calculated value is greater than or equal to 60ml/min, and&#xD;
&#xD;
             - routine urine urine protein negative or 24 hour urinary protein quantity is less&#xD;
             than or equal to 1g;&#xD;
&#xD;
         16. Within 7 days before treatment, the international normalized ratio (INR) is less or&#xD;
             equal to 1.5 times ULN, and partial thromboplastin time (PTT or aPTT) less than 1.5&#xD;
             times ULN;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Mixed non-small cell and small cell carcinoma, large cell carcinoma, adenosquamous&#xD;
             carcinoma;&#xD;
&#xD;
          2. Within 3 months before the election has a clear history of hemoptysis, that is, a&#xD;
             single hemoptysis more than 2ml blood;&#xD;
&#xD;
          3. Images show signs of tumor invasion into the large blood vessels;&#xD;
&#xD;
          4. Patients with symptomatic central nervous system metastasis or intratumoral&#xD;
             hemorrhage, the patient can not be selected regardless of whether or not to receive&#xD;
             the relevant treatment;&#xD;
&#xD;
          5. Received chest radiotherapy within 28 days prior to enrollment;&#xD;
&#xD;
          6. Received a large number of surgical operations (including thoracotomy biopsy) or have&#xD;
             a major trauma within 28 days prior to enrollment;&#xD;
&#xD;
          7. Current or resent (within the first 10 days of receiving the first dose bevacizumab)&#xD;
             using aspirin (&gt; 325 mg / day);&#xD;
&#xD;
          8. Current or recent (within the first 10 days of receiving the first dose bevacizumab)&#xD;
             the use of full dose oral or parenteral anticoagulant or thrombolytic therapy.Allow&#xD;
             prophylactic use of anticoagulants;&#xD;
&#xD;
          9. Medical history or examination results indicate that patients with hereditary bleeding&#xD;
             tendency or coagulopathy may increase the risk of bleeding;&#xD;
&#xD;
         10. Uncontrolled hypertension (systolic blood pressure&gt; 150 mmHg and / or diastolic blood&#xD;
             pressure&gt; 100 mmHg);&#xD;
&#xD;
         11. Previous hypertensive crisis or hypertensive encephalopathy patients;&#xD;
&#xD;
         12. Cardiovascular disease with clinical significance, including but not limited to&#xD;
             CVA(cerebral vascular accident) or TIA（transient ischemic attack） (≤ 6 months before&#xD;
             admission), myocardial infarction (≤ 6 months before enrollment), unstable angina, New&#xD;
             York Heart Association classification ≥ Class II Congestive heart failure, need to be&#xD;
             treated during the study and may interfere with the study of treatment, or drug can&#xD;
             not control the serious arrhythmia;&#xD;
&#xD;
         13. Significant vascular disease (including but not limited to aortic aneurysm or proximal&#xD;
             arterial thrombosis requiring surgery repair) within 6 months prior to enrollment;&#xD;
&#xD;
         14. Non-curative wounds, active peptic ulcers or fractures;&#xD;
&#xD;
         15. There was a history of abdominal fistula, gastrointestinal perforation, or&#xD;
             intraperitoneal abscess within 6 months of enrollment;&#xD;
&#xD;
         16. Women who had a complete uterus (except for menopausal status over the last 24 months)&#xD;
             during the six months after the study and at the last administration of bevacizumab,&#xD;
             but did not use effective contraceptive methods (no contraindications to use&#xD;
             background chemotherapy Drugs in the case of oral contraceptives, intrauterine&#xD;
             devices, barrier contraceptives combined with spermicidal gels or sterilization&#xD;
             surgery). During the study period and the last administration of bevacizumab within 90&#xD;
             days, men who did not agree to use effective contraceptive methods;&#xD;
&#xD;
         17. Pregnant and lactating women;&#xD;
&#xD;
         18. Received any other test medication or participated in another clinical trial within 28&#xD;
             days prior to enrollment;&#xD;
&#xD;
         19. Known hypersensitivity to bevacizumab or any of its excipients and any&#xD;
             chemotherapeutic ingredients;&#xD;
&#xD;
         20. Signs of persistent or active infection requiring intravenous antibiotic therapy;&#xD;
             other diseases, neurological or metabolic dysfunction; contraindications in the&#xD;
             results of medical examination or laboratory findings or the use of a study drug or a&#xD;
             patient at a high risk of treating the high risk associated with complications&#xD;
             Suspicious disease or symptoms;&#xD;
&#xD;
         21. Tracheal - esophageal fistula or bronchial - pleural fistula;&#xD;
&#xD;
         22. Malignant tumor other than NSCLC within 5 years before enrollment, except for the&#xD;
             adequately treated cervical carcinoma in situ, basal cell or squamous cell skin&#xD;
             cancer, localized prostate cancer and ductal carcinoma in situ after radical&#xD;
             resection;&#xD;
&#xD;
         23. Medical history or examination results showed thrombotic disease within 6 months&#xD;
             before enrollment;&#xD;
&#xD;
         24. Patients with mental illness or no self-judgment.&#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_official>
    <last_name>Yixin Zeng, Doctor</last_name>
    <role>Study Chair</role>
    <affiliation>Beijing Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Bin Ai, Docter</last_name>
    <phone>+86 10 85132542</phone>
    <email>docaibin@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Xu Li, Master</last_name>
    <phone>+86 10 85136714</phone>
    <email>li-xu@vip.sina.com</email>
  </overall_contact_backup>
  <reference>
    <citation>Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14;355(24):2542-50. doi: 10.1056/NEJMoa061884. Erratum In: N Engl J Med. 2007 Jan 18;356(3):318.</citation>
    <PMID>17167137</PMID>
  </reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>July 20, 2017</study_first_submitted>
  <study_first_submitted_qc>August 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2017</study_first_posted>
  <last_update_submitted>August 2, 2017</last_update_submitted>
  <last_update_submitted_qc>August 2, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 7, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Beijing Hospital</investigator_affiliation>
    <investigator_full_name>Bin Ai</investigator_full_name>
    <investigator_title>Deputy chief physician</investigator_title>
  </responsible_party>
  <keyword>advanced pulmonary adenocarcinoma</keyword>
  <keyword>Bevacizumab</keyword>
  <keyword>First line chemotherapy</keyword>
  <keyword>Stable disease</keyword>
  <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>Bevacizumab</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/NCT03240549
org study id: 121-2016007
nct id: NCT03240549
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Previous studies have shown that the addition of bevacizumab to the standard first-line
      platinum-based combination therapy can improve the objective response rate of patients with
      advanced non-squamous non-small cell lung cancer by 20% to 28% and improve survival. Data
      from these published literatures suggest that the improvement in objective response rates is
      due mainly to patients with stable disease of chemotherapy. It has been reported that 15% of
      patients achieved objective remission after continuing treatment with the regimen after
      receiving 2 cycles of platinum-based combination chemotherapy. Therefore, the use of 2 cycles
      of chemotherapy after stabilization of patients with bevacizumab, hoping to improve the
      objective response rate of such patients 20%, and may improve survival. For the above
      reasons, design this study to validate our hypothesis.
Previous studies have shown that the addition of bevacizumab to the standard first-line
      platinum-based combination therapy can improve the objective response rate of patients with
      advanced non-squamous non-small cell lung cancer by 20% to 28% and improve survival. Data
      from these published literatures suggest that the improvement in objective response rates is
      due mainly to patients with stable disease of chemotherapy. It has been reported that 15% of
      patients achieved objective remission after continuing treatment with the regimen after
      receiving 2 cycles of platinum-based combination chemotherapy. Therefore, the use of 2 cycles
      of chemotherapy after stabilization of patients with bevacizumab, hoping to improve the
      objective response rate of such patients 20%, and may improve survival. For the above
      reasons, design this study to validate our hypothesis.

      So a prospective cohort study has been designed to confirm this hypothesis, patients with
      advanced pulmonary adenocarcinoma who are stable after two cycles of platinum-based
      combination chemotherapy are objects of this study, and they can choose to continue the
      previous treatment regimen according to the guideline or adding bevacizumab to the regimen
      independently until the progression or intolerance of toxicity, or 4 to 6 cycles of
      chemotherapy in stable disease. The objective response rate in these two groups who received
      different treatment is the primary endpoint and the toxicity, quality of life, the
      progression free survival are the second endpoints.
allocation: Non-Randomized
intervention model: Factorial Assignment
intervention model description: Prospective cohort study
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate
time frame: Assessment of the response should be done from the written consent to the 3 month after the last patient inrolled in the study, assessed up to 24 months.
description: The percentage of patients who was assessed as complete response and partial response according RECIST (Response Evaluation In Solid Tumors).
measure: Duration of Response Duration of Response
time frame: The start point was the first remission until the date of first documented progression or date of death from any cause, which came first, assessed up to 30 months.
description: The duration in responsive patients from the first remission to the progression.
measure: Progression Free Survival.
time frame: The progression free survival was start from the written consent to the date of first documented progression or date of death from any cause, which came first,assessed up to 30 months.
description: The time from the day written consent to the first date of objective progression or death from any cause.
measure: Adverse Effects.
time frame: Assessment should be done from the written consent to the date 28 days after the last chemotherapy, assessed up to 24 months.
description: The adverse effects of the treatment especially in hematology,cardiovascular system and renal system according the CTCAE 4.0, and the SAE(serious adverse events) in the treatment and follow up.
measure: Quality of Life.
time frame: Assessment should be done from the written consent to the finish of this study, assessed up to 36 months.
description: The quality of life should be assessed in the study using FACT-L(Functional Assessment of Cancer Therapy - Lung).
arm group label: conventional therapy group
arm group type: No Intervention
description: Treatment with previous regimen of combined chemotherapy
arm group label: bevacizumab group
arm group type: Experimental
description: Adding bevacizumab to the previous regimen of combined chemotherapy
intervention type: Drug
intervention name: bevacizumab
description: The patients in conventional group continued the previous chemotherapy,and the patients in experimental group received adding bevacizumab to previous chemotherapy regimen.
arm group label: bevacizumab group
other name: avastin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Yixin Zeng, Doctor
role: Study Chair
affiliation: Beijing Hospital
last name: Bin Ai, Docter
phone: +86 10 85132542
email: docaibin@163.com
last name: Xu Li, Master
phone: +86 10 85136714
email: li-xu@vip.sina.com
citation: Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14;355(24):2542-50. doi: 10.1056/NEJMoa061884. Erratum In: N Engl J Med. 2007 Jan 18;356(3):318.
PMID: 17167137
responsible party type: Principal Investigator
investigator affiliation: Beijing Hospital
investigator full name: Bin Ai
investigator title: Deputy chief physician
mesh term: Lung Neoplasms
mesh term: Bevacizumab
sharing ipd: No