xml: <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/NCT06041776</url>
    </required_header>
    <id_info>
      <org_study_id>BD-BF-III01</org_study_id>
      <nct_id>NCT06041776</nct_id>
    </id_info>
    <brief_title>Postoperative Adjuvant Therapy of Befotertinib vs Icotinib in Stage IB-IIIB Non-small Cell Lung Cancer With Positive EGFR Sensitive Mutations</brief_title>
    <official_title>A Multicenter, Randomized, Controlled, Double Blind, Double Simulated, Phase III Clinical Study of Befotertinib vs Icotinib for Postoperative Adjuvant Treatment of IB-IIIB (T3N2M0) Stage Non Small Cell Lung Cancer With Positive EGFR Sensitive Mutations</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Betta Pharmaceuticals Co., Ltd.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Betta Pharmaceuticals Co., Ltd.</source>
    <oversight_info>
      <has_dmc>Yes</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 multicenter, randomized, controlled, double-blind, double-simulated, Phase III study is&#xD;
        designed to evaluate the efficacy and safety of Befotertinib compared with Icotinib as&#xD;
        adjuvant treatment in EGFR-sensitive mutation-positive stage IB-IIIB (T3N2M0) non-small cell&#xD;
        lung cancer after surgical resection.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">April 30, 2023</start_date>
    <completion_date type="Anticipated">November 30, 2029</completion_date>
    <primary_completion_date type="Anticipated">April 30, 2028</primary_completion_date>
    <phase>Phase 3</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Disease free survival (DFS) evaluated by investigator in patients with stage II-IIIB (T3N2M0)</measure>
      <time_frame>up to 5 years</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>DFS evaluated by investigator in patients with stage IB-IIIB (T3N2M0)</measure>
      <time_frame>up to 5 years</time_frame>
    </secondary_outcome>
    <other_outcome>
      <measure>DFS rate at 2 years</measure>
      <time_frame>Assessed at 2 years</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>DFS rate at 3 years</measure>
      <time_frame>Assessed at 3 years</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>DFS rate at 5 years</measure>
      <time_frame>Assessed at 5 years</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>Assessed at 5 years</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>OS rate at 5 years</measure>
      <time_frame>up to 5 years</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Treatment-Emergent Adverse Event (TEAE)</measure>
      <time_frame>Until 28 days after the last dosing</time_frame>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">570</enrollment>
    <condition>Non-Small Cell Lung Cancer；EGFR Sensitive Mutation；Adjuvant Therapy</condition>
    <arm_group>
      <arm_group_label>Befotertinib + Icotinib placebo</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Befotertinib (75 mg or 100 mg orally, once daily) and Icotinib placebo(125 mg orally, three times daily)，in accordance with the randomization schedule</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Icotinib + Befotertinib placebo</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Icotinib (125 mg orally, three times daily) and Befotertinib placebo (75 mg or 100 mg orally, once daily)，in accordance with the randomization schedule</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Befotertinib + Icotinib placebo</intervention_name>
      <description>The initial dose of Befotertinib is 75 mg orally once daily (QD) for 21 days, and then increased to 100 mg orally QD in the absence of serious side effects , CTCAE grade ≥ 2 headache or thrombocytopenia during the 21 days.&#xD;
  Befotertinib can be taken on an empty stomach or after meals, and the medication is used until the disease relapses or intolerable toxicity occurs, or the treatment lasts for 3 years (disease recurrence includes local recurrence and/or distant metastasis)&#xD;
  Icotinib placebo 125 mg three times daily, on an empty stomach or in combination with food, use medication until the disease relapses or intolerable toxicity occurs or treatment lasts for 2 years (disease recurrence includes local recurrence and/or distant metastasis).</description>
      <arm_group_label>Befotertinib + Icotinib placebo</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Icotinib + Befotertinib placebo</intervention_name>
      <description>Icotinib 125 mg three times daily, on an empty stomach or in combination with food, use medication until the disease relapses or intolerable toxicity occurs or treatment lasts for 2 years (disease recurrence includes local recurrence and/or distant metastasis).&#xD;
  The initial dose of Befotertinib placebo is 75 mg orally once daily (QD) for 21 days, and then increased to 100 mg orally QD in the absence of serious side effects , CTCAE grade ≥ 2 headache or thrombocytopenia during the 21 days.&#xD;
  Befotertinib placebo can be taken on an empty stomach or after meals, and the medication is used until the disease relapses or intolerable toxicity occurs, or the treatment lasts for 3 years (disease recurrence includes local recurrence and/or distant metastasis.</description>
      <arm_group_label>Icotinib + Befotertinib placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Willingness to sign informed consent prior to any study specific procedures, and&#xD;
               ability to with scheduled visits, treatment plans, laboratory tests, and other study&#xD;
               procedures.&#xD;
  &#xD;
            2. Male or female, aged at least 18 years.&#xD;
  &#xD;
            3. Histologically confirmed primary NSCLC, and mainly non-squamous cell carcinoma&#xD;
               (including mixed type carcinoma mainly composed of adenocarcinoma components).&#xD;
  &#xD;
            4. MRI or CT scan of the brain must be done prior to surgery，and it must be confirmed&#xD;
               that there is no brain metastasis. For subjects who have not been examined before&#xD;
               surgery, if brain MRI or CT scans are performed before the first use of the&#xD;
               investigational drug and it is confirmed that there is no brain metastasis, they can&#xD;
               still be enrolled.&#xD;
  &#xD;
            5. Complete resection of histologically confirmed Stage IB, II, IIIA or IIIB(T3N2M0)&#xD;
               according to the TNM staging system for lung cancer (AJCC/UICC 8th edition), with&#xD;
               negative margins.&#xD;
  &#xD;
            6. Confirmation by the central laboratory that the tumor harbors one of the 2 common EGFR&#xD;
               mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either&#xD;
               alone or in combination with other EGFR mutations including T790M.&#xD;
  &#xD;
            7. Patients who fully recover from surgery during randomization (any surgery must achieve&#xD;
               complete postoperative wound healing) and should receive adjuvant treatment within&#xD;
               4-10 weeks after surgery.&#xD;
  &#xD;
            8. ECOG-PS score of 0 or 1 and did not deteriorate 2 weeks before the first&#xD;
               administration of the investigational drug, with a minimum expected survival greater&#xD;
               than 12 weeks.&#xD;
  &#xD;
            9. Female subjects with fertility need to have a negative serum pregnancy test during&#xD;
               screening.&#xD;
  &#xD;
           10. Female subjects who have possibility of becoming pregnant, as well as male subjects&#xD;
               whose partners are women of childbearing age, must use a highly effective&#xD;
               contraceptive method (such as oral contraceptives, intrauterine devices, abstinence or&#xD;
               barrier contraception combined with spermicides) throughout the study and continue to&#xD;
               use contraception for 3 months after the end of treatment.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. There are unresectable or metastatic diseases, pathological reports showing positive&#xD;
               surgical margins under the microscope or extranodal invasion, or lesions left after&#xD;
               surgery, or suspicious lesions determined by imaging after surgery. Subjects receiving&#xD;
               only wedge resection.&#xD;
  &#xD;
            2. Upper lung groove cancer.&#xD;
  &#xD;
            3. Patient with complete resection of the right lung with NSCLC.&#xD;
  &#xD;
            4. Malignancies other than NSCLC within 5 years prior to first dosage, except for&#xD;
               malignant tumors that can be cured after treatment (including but not limited to fully&#xD;
               treated thyroid cancer, cervical carcinoma in situ, basal or squamous cell skin&#xD;
               cancer, or breast ductal carcinoma in situ treated with radical surgery).&#xD;
  &#xD;
            5. Received systematic anti-tumor therapy, including chemotherapy, radiotherapy or&#xD;
               targeted therapy (including but not limited to monoclonal antibodies, small molecule&#xD;
               tyrosine kinase inhibitors), immunotherapy, investigational therapy, etc., before&#xD;
               being enrolled in this study.&#xD;
  &#xD;
            6. Within 3 weeks prior to the first administration of the investigational drug, the&#xD;
               patient underwent major surgery (including primary tumor surgery, craniotomy,&#xD;
               thoracotomy, or laparotomy, excluding vascular pathway establishment procedures).&#xD;
  &#xD;
            7. Within 14 days prior to first dose of the investigational drug, Traditional Chinese&#xD;
               medicine with anti-tumor indications have been received.&#xD;
  &#xD;
            8. After the start of the study, any form of systemic or local anti-tumor treatment&#xD;
               (including maintenance therapy with another drug, radiotherapy, and/or surgical&#xD;
               resection) is still required.&#xD;
  &#xD;
            9. Clinically significant cardiovascular diseases, including:&#xD;
  &#xD;
                 1. QTcF interval &gt;450 ms (men) or &gt;470 ms (women), symptomatic bradycardia (&lt;45&#xD;
                    beats /min), or other significant ECG abnormalities as determined by the&#xD;
                    investigator (e.g., complete left bundle branch block, third-degree heart block,&#xD;
                    second-degree heart block, PR interval &gt;250 msec).&#xD;
  &#xD;
                 2. Echocardiography showed LVEF &lt;50%.&#xD;
  &#xD;
                 3. Hypertension was clinically uncontrollable (e.g., blood pressure &gt;160/100 mmHg;&#xD;
                    Except that isolated elevated readings that were determined by the investigators&#xD;
                    to be clinically insignificant or controllable hypertension.)&#xD;
  &#xD;
               Within 6 months before the first medication, there were the following situations:&#xD;
  &#xD;
                 1. Congestive heart failure (New York Heart Association rating III or IV).&#xD;
  &#xD;
                 2. Arrhythmias or conduction abnormalities that require medication treatment. Note:&#xD;
                    Patients with drug-controlled atrial fibrillation/flutter, as well as those with&#xD;
                    pacemaker controlled arrhythmia, can be selected.&#xD;
  &#xD;
                 3. Severe/unstable angina, coronary artery/peripheral bypass grafting, or myocardial&#xD;
                    infarction (Note: Severe angina is classified as Grade III or IV by the Canadian&#xD;
                    Society of Cardiology).&#xD;
  &#xD;
                 4. Cerebrovascular accidents or transient ischemic attacks, transient myocardial&#xD;
                    ischemia.&#xD;
  &#xD;
           10. Previous history of concomitant interstitial lung disease (ILD), drug-induced ILD,&#xD;
               radiation pneumonia requiring hormone therapy, or clinical evidence of concomitant&#xD;
               active interstitial lung disease.&#xD;
  &#xD;
           11. Patients who have a history of thrombosis or are currently present with thrombosis or&#xD;
               have a potential risk of thrombosis assessed by the investigator.&#xD;
  &#xD;
           12. Any clinical evidence of a serious active infection, or any serious concomitant&#xD;
               disease that may affect the subject's acceptance of investigational drugs, such as&#xD;
               active bleeding predisposition, active hepatitis B, hepatitis C, or tuberculosis,&#xD;
               syphilis, or HIV antibody positive.&#xD;
  &#xD;
           13. There are serious gastrointestinal functional abnormalities in clinical practice that&#xD;
               may affect drug intake, transportation, or absorption, such as inability to take&#xD;
               medication orally, uncontrollable nausea or vomiting, history of extensive&#xD;
               gastrointestinal resection, untreated recurrent diarrhea, atrophic gastritis,&#xD;
               untreated stomach diseases requiring long-term use of proton pump inhibitors,&#xD;
               gastrointestinal obstruction, active diverticulitis, Crohn's disease, ulcerative&#xD;
               colitis, etc.&#xD;
  &#xD;
           14. Any of the following laboratory indicators are abnormal:&#xD;
  &#xD;
                 1. Absolute neutrophil count (ANC)&lt;1.5 × 10^9/L&#xD;
  &#xD;
                 2. Platelet count (PLT)&lt;100 × 10^9/L&#xD;
  &#xD;
                 3. Hemoglobin (Hb) &lt; 90g/L (Note: to meet the required hemoglobin level, blood&#xD;
                    transfusion is allowed, but it must be completed at least 14 days before&#xD;
                    screening)&#xD;
  &#xD;
                 4. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST)&gt;2.5 times the&#xD;
                    upper limit of normal value (ULN)&#xD;
  &#xD;
                 5. Total bilirubin&gt;1.5 times ULN&#xD;
  &#xD;
                 6. Serum creatinine (SCr)&gt;1.5 times ULN or creatinine clearance rate&lt;50ml/min&#xD;
  &#xD;
                 7. International standardized ratio (INR) or activated partial thromboplastin time&#xD;
                    (APTT)&gt;1.5 times ULN&#xD;
  &#xD;
           15. History of hypersensitivity to the investigational drug Befotertinib, icotinib and&#xD;
               their inactive excipients.&#xD;
  &#xD;
           16. Within one week before the first administration of the investigational drug, it is&#xD;
               currently in use or needs to be combined with CYP3A strong inhibitors or inducers&#xD;
               during the study period.&#xD;
  &#xD;
           17. Patients who are still using warfarin within 7 days prior to initial dosing (low&#xD;
               molecular weight heparin sodium is allowed).&#xD;
  &#xD;
           18. Participating in clinical research and receiving treatment with the study drug or&#xD;
               research device, or participating in clinical research and receiving treatment with&#xD;
               the study drug or research device within 4 weeks before the first administration, or&#xD;
               planning to participate in any other clinical trial during this study period.&#xD;
  &#xD;
           19. Inoculate with a live vaccine within 180 days before the first medication.&#xD;
  &#xD;
           20. Researchers believe that it may affect protocol compliance or affect the signing of&#xD;
               informed consent forms by participants (such as a history of mental illness or drug&#xD;
               abuse, alcoholism or other addiction), or any other clinically significant disease or&#xD;
               condition that is not suitable for participation in this clinical trial (such as&#xD;
               laboratory abnormal results, clinically active diverticulitis, abdominal abscess).&#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_official>
      <last_name>Shun Lu, M.D.</last_name>
      <role>Study Chair</role>
      <affiliation>Shanghai Chest Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Lihong Tian, Master</last_name>
      <phone>+86 15011392991</phone>
      <email>lihong.tian@bettapharma.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Peking University International Hospital</name>
        <address>
          <city>Beijing</city>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>Jiangsu Cancer Hospital</name>
        <address>
          <city>Nanjing</city>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>Shanghai chest hospital</name>
        <address>
          <city>Shanghai</city>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 12, 2023</study_first_submitted>
    <study_first_submitted_qc>September 12, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 18, 2023</study_first_posted>
    <last_update_submitted>September 12, 2023</last_update_submitted>
    <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</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>
      <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
      <mesh_term>Hypersensitivity</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06041776
  org study id: BD-BF-III01
  nct id: NCT06041776
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This multicenter, randomized, controlled, double-blind, double-simulated, Phase III study is
        designed to evaluate the efficacy and safety of Befotertinib compared with Icotinib as
        adjuvant treatment in EGFR-sensitive mutation-positive stage IB-IIIB (T3N2M0) non-small cell
        lung cancer after surgical resection.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Disease free survival (DFS) evaluated by investigator in patients with stage II-IIIB (T3N2M0)
  time frame: up to 5 years
  measure: DFS evaluated by investigator in patients with stage IB-IIIB (T3N2M0)
  time frame: up to 5 years
  measure: DFS rate at 2 years
  time frame: Assessed at 2 years
  measure: DFS rate at 3 years
  time frame: Assessed at 3 years
  measure: DFS rate at 5 years
  time frame: Assessed at 5 years
  measure: Overall survival (OS)
  time frame: Assessed at 5 years
  measure: OS rate at 5 years
  time frame: up to 5 years
  measure: Treatment-Emergent Adverse Event (TEAE)
  time frame: Until 28 days after the last dosing
  arm group label: Befotertinib + Icotinib placebo
  arm group type: Experimental
  description: Befotertinib (75 mg or 100 mg orally, once daily) and Icotinib placebo(125 mg orally, three times daily)，in accordance with the randomization schedule
  arm group label: Icotinib + Befotertinib placebo
  arm group type: Active Comparator
  description: Icotinib (125 mg orally, three times daily) and Befotertinib placebo (75 mg or 100 mg orally, once daily)，in accordance with the randomization schedule
  intervention type: Drug
  intervention name: Befotertinib + Icotinib placebo
  description: The initial dose of Befotertinib is 75 mg orally once daily (QD) for 21 days, and then increased to 100 mg orally QD in the absence of serious side effects , CTCAE grade ≥ 2 headache or thrombocytopenia during the 21 days.
  Befotertinib can be taken on an empty stomach or after meals, and the medication is used until the disease relapses or intolerable toxicity occurs, or the treatment lasts for 3 years (disease recurrence includes local recurrence and/or distant metastasis)
  Icotinib placebo 125 mg three times daily, on an empty stomach or in combination with food, use medication until the disease relapses or intolerable toxicity occurs or treatment lasts for 2 years (disease recurrence includes local recurrence and/or distant metastasis).
  arm group label: Befotertinib + Icotinib placebo
  intervention type: Drug
  intervention name: Icotinib + Befotertinib placebo
  description: Icotinib 125 mg three times daily, on an empty stomach or in combination with food, use medication until the disease relapses or intolerable toxicity occurs or treatment lasts for 2 years (disease recurrence includes local recurrence and/or distant metastasis).
  The initial dose of Befotertinib placebo is 75 mg orally once daily (QD) for 21 days, and then increased to 100 mg orally QD in the absence of serious side effects , CTCAE grade ≥ 2 headache or thrombocytopenia during the 21 days.
  Befotertinib placebo can be taken on an empty stomach or after meals, and the medication is used until the disease relapses or intolerable toxicity occurs, or the treatment lasts for 3 years (disease recurrence includes local recurrence and/or distant metastasis.
  arm group label: Icotinib + Befotertinib placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Shun Lu, M.D.
  role: Study Chair
  affiliation: Shanghai Chest Hospital
  last name: Lihong Tian, Master
  phone: +86 15011392991
  email: lihong.tian@bettapharma.com
  facility: 
  status: Recruiting
  facility: 
  status: Recruiting
  facility: 
  status: Recruiting
  country: China
  responsible party type: Sponsor
  mesh term: Lung Neoplasms
  mesh term: Carcinoma, Non-Small-Cell Lung
  mesh term: Hypersensitivity
  sharing ipd: No