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/NCT06020989</url>
    </required_header>
    <id_info>
      <org_study_id>4-2023-0795</org_study_id>
      <nct_id>NCT06020989</nct_id>
    </id_info>
    <brief_title>Lazertinib and Chemotherapy Combination in EGFR-mutant NSCLC Patients Without ctDNA Clearance After lead-in Lazertinib Monotherapy</brief_title>
    <acronym>CHAMELEON</acronym>
    <official_title>A Randomized, Phase 2 Trial of Lazertinib and Chemotherapy Combination in EGFR-mutant NSCLC Patients Without ctDNA Clearance After lead-in Lazertinib Monotherapy (CHAMELEON)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Yonsei University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Yonsei 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>
        Lazertinib is an oral third-generation irreversible tyrosine kinase inhibitor (TKI) that has&#xD;
        proved to selectively inhibit EGFR-TKI sensitizing mutations (exon 19 deletion or exon 21&#xD;
        L858R) and be effective in patients with central nervous system (CNS) metastases. However,&#xD;
        all patients eventually experience disease progression. For patients with MRD, lazertinib&#xD;
        plus cytotoxic anticancer drug can prolong the duration of response or even induce complete&#xD;
        cure, indicating this combined treatment strategy is considered the safest and most&#xD;
        effective.&#xD;
  &#xD;
        The objective of this phase 2 prospective two-arm clinical trial is to evaluate the safety&#xD;
        and efficacy of lazertinib alone or in combination with cytotoxic chemotherapy in EGFR-mutant&#xD;
        (exon 19 deletion or exon 21 L858R) NSCLC patients without ctDNA clearance after lead-in&#xD;
        lazertinib. If anticancer drugs are used only for patients with MRD, the risk of resistance&#xD;
        development will decrease, improving PFS.&#xD;
  &#xD;
        Hypothesis: to evaluate the efficacy defined as the PFS rate of lazertinib alone or in&#xD;
        combination with a cytotoxic anticancer drug in EGFR-mutant NSCLC patients without ctDNA&#xD;
        clearance after lead-in lazertinib monotherapy.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">December 2025</completion_date>
    <primary_completion_date type="Anticipated">September 2024</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</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 100 months</time_frame>
      <description>PFS is measured from the date of start of study to the date of disease progression or death from any cause.</description>
    </primary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">129</enrollment>
    <condition>Non Small Cell Lung Cancer</condition>
    <arm_group>
      <arm_group_label>A</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Lazertinib + chemotherapy combination</description>
    </arm_group>
    <arm_group>
      <arm_group_label>B</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Lazertinib monotherapy</description>
    </arm_group>
    <arm_group>
      <arm_group_label>C</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Lazertinib monotherapy</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Lazertinib+Pemetrexed+Carboplatin</intervention_name>
      <description>Arm A will receive Lazertinib and Pemetrexed, Carboplatin combination. Lazertinib will be given 240 mg once a day daily PO until disease progression or unacceptable toxicity. Pemetrexed(500 mg/m2) will be administered IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity. Carboplatin(AUC5) will be administered IV infusions on Day 1 of each 21-day cycle until 4 cycles.</description>
      <arm_group_label>A</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Lazertinib</intervention_name>
      <description>Lazertinib will be given 240 mg once a day daily PO until disease progression or unacceptable toxicity.</description>
      <arm_group_label>B</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Lazertinib</intervention_name>
      <description>Lazertinib will be given 240 mg once a day daily PO until disease progression or unacceptable toxicity.</description>
      <arm_group_label>C</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Patients with histologically confirmed recurrent or metastatic non-squamous NSCLC&#xD;
               without previous treatment experience&#xD;
  &#xD;
            2. Presence of the sensitising EGFR-mutation (exon 19 deletion and/or L858R) detected by&#xD;
               an accredited laboratory.&#xD;
  &#xD;
            3. Measurable disease as defined according to RECIST v1.1&#xD;
  &#xD;
            4. Age ≥19 years&#xD;
  &#xD;
            5. ECOG performance status 0-2&#xD;
  &#xD;
            6. Life expectancy ≥12 months&#xD;
  &#xD;
            7. Adequate haematological function:&#xD;
  &#xD;
                 1. Haemoglobin ≥90 g/L&#xD;
  &#xD;
                 2. Absolute neutrophil count (ANC) ≥ 1.5× 109/L&#xD;
  &#xD;
                 3. Platelet count ≥100× 109/L&#xD;
  &#xD;
            8. Adequate renal function:&#xD;
  &#xD;
                 1. Serum creatinine ≤1.5x ULN or creatinine clearance ≥50 mL/min (calculated&#xD;
                    according to Cockcroft-Gault formula, see below).&#xD;
  &#xD;
                 2. Confirmation of creating clearance is only required when serum creatinine is&#xD;
                    &gt;1.5x ULN.&#xD;
  &#xD;
               Cockcroft-Gault formula:&quot;mL&quot; /&quot;min&quot; &quot;=&quot; (&quot;140-age&quot; [&quot;years&quot; ])&quot;×actual body weight &quot;&#xD;
               [&quot;kg&quot; ]/(&quot;72×&quot; 〖&quot;Creatinine&quot; 〗_&quot;serum&quot; &quot; &quot; (&quot;mg&quot; /&quot;dL&quot; ) ) &quot;(×0.85 if female)&quot;&#xD;
  &#xD;
            9. Adequate liver function:&#xD;
  &#xD;
                 1. ALT and AST ≤2.5× ULN. If the patient has liver metastases, ALT and AST must be&#xD;
                    ≤5× ULN&#xD;
  &#xD;
                 2. Total serum bilirubin ≤1.5× ULN. If the patient has documented Gilbert's syndrome&#xD;
                    (unconjugated hyperbilirubinaemia) ≤3× ULN.&#xD;
  &#xD;
           10. Women of childbearing potential, including women who had their last menstruation in&#xD;
               the last 2 years, must have a negative urinary or serum pregnancy test within 7 days&#xD;
               before enrolment.&#xD;
  &#xD;
           11. Written IC for protocol treatment must be signed and dated by the patient and the&#xD;
               investigator prior to any trial-related intervention.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Presence of leptomeningeal metastases&#xD;
  &#xD;
            2. Symptomatic spinal cord compression&#xD;
  &#xD;
            3. Currently receiving (or unable to stop use prior to receiving the first dose of&#xD;
               lazertinib treatment) medications or herbal supplements known to be potent CYP3A4&#xD;
               inducers that cannot be stopped before enrolment and for the duration of the trial.&#xD;
  &#xD;
            4. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled&#xD;
               hypertension and active bleeding diatheses, which in the investigator's opinion makes&#xD;
               it undesirable for the patient to participate in the trial or which would jeopardise&#xD;
               compliance with the protocol, or active infection including hepatitis B, hepatitis C&#xD;
               and human immunodeficiency virus (HIV). Screening for chronic conditions is not&#xD;
               required.&#xD;
  &#xD;
            5. Patients with a resolved or chronic HBV infection are eligible if they are:&#xD;
  &#xD;
                 1. Negative for HBsAg and positive for hepatitis B core antibody [anti-HBc IgG]; or&#xD;
  &#xD;
                 2. Positive for HBsAg, negative for HBeAg but for &gt;6 months have had transaminases&#xD;
                    levels below ULN and HBV DNA levels below 2000 IU/mL (i.e., are in an inactive&#xD;
                    carrier state).&#xD;
  &#xD;
            6. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to&#xD;
               swallow the formulated product or previous significant bowel resection that would&#xD;
               preclude adequate absorption of lazertinib&#xD;
  &#xD;
            7. Any of the following cardiac criteria:&#xD;
  &#xD;
                 1. QTcF &gt;470 msec obtained from 3 ECGs, using the screening clinic ECG machine&#xD;
                    derived QTc value (QTcF: corrected QT interval using Fridericia's formula).&#xD;
  &#xD;
                 2. Any clinically important abnormalities in rhythm, conduction or morphology of&#xD;
                    resting ECG (e.g., complete left bundle branch block, third degree heart block or&#xD;
                    second-degree heart block).&#xD;
  &#xD;
                 3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic&#xD;
                    events such as heart failure, hypokalaemia, congenital long QT syndrome, family&#xD;
                    history of long QT syndrome or unexplained sudden death under 40 years of age in&#xD;
                    first degree relatives or any concomitant medication known to prolong the QT&#xD;
                    interval and cause Torsades de Pointes (TdP).&#xD;
  &#xD;
            8. Past medical history of ILD, drug induced ILD, interstitial pneumonitis which required&#xD;
               steroid treatment, or any evidence of clinically active ILD&#xD;
  &#xD;
            9. History of hypersensitivity to active or inactive excipients of lazertinib or drugs&#xD;
               with a similar chemical structure or class to lazertinib.&#xD;
  &#xD;
           10. Patients who should not participate in the trial at the investigator's discretion as&#xD;
               they are unlikely to comply with trial procedures, restrictions, and requirements for&#xD;
               pregnant or lactation women.&#xD;
  &#xD;
           11. Both sexually active men and women of childbearing potential who are not willing to&#xD;
               use an effective contraceptive method (Please refer to 8.3 for highly effective&#xD;
               contraceptive methods) during the trial and up to 6 months after discontinuing&#xD;
               lazertinib treatment.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>19 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Sun Min Lim</last_name>
      <role>Principal Investigator</role>
      <affiliation>Yonsei University Health System, Severance Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Sun Min Lim</last_name>
      <phone>+82-2227-8068</phone>
      <email>limlove2008@yuhs.ac</email>
    </overall_contact>
    <location>
      <facility>
        <name>Yonsei University Health System, Severance Hospital</name>
        <address>
          <city>Seoul</city>
          <country>Korea, Republic of</country>
        </address>
      </facility>
      <contact>
        <last_name>Sun Min Lim</last_name>
        <phone>+82-2227-8068</phone>
        <email>limlove2008@yuhs.ac</email>
      </contact>
    </location>
    <location_countries>
      <country>Korea, Republic of</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 27, 2023</study_first_submitted>
    <study_first_submitted_qc>August 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 1, 2023</study_first_posted>
    <last_update_submitted>August 31, 2023</last_update_submitted>
    <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 1, 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>Carcinoma, Non-Small-Cell Lung</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carboplatin</mesh_term>
      <mesh_term>Pemetrexed</mesh_term>
      <mesh_term>Lazertinib</mesh_term>
    </intervention_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/NCT06020989
  org study id: 4-2023-0795
  nct id: NCT06020989
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Lazertinib is an oral third-generation irreversible tyrosine kinase inhibitor (TKI) that has
        proved to selectively inhibit EGFR-TKI sensitizing mutations (exon 19 deletion or exon 21
        L858R) and be effective in patients with central nervous system (CNS) metastases. However,
        all patients eventually experience disease progression. For patients with MRD, lazertinib
        plus cytotoxic anticancer drug can prolong the duration of response or even induce complete
        cure, indicating this combined treatment strategy is considered the safest and most
        effective.
  
        The objective of this phase 2 prospective two-arm clinical trial is to evaluate the safety
        and efficacy of lazertinib alone or in combination with cytotoxic chemotherapy in EGFR-mutant
        (exon 19 deletion or exon 21 L858R) NSCLC patients without ctDNA clearance after lead-in
        lazertinib. If anticancer drugs are used only for patients with MRD, the risk of resistance
        development will decrease, improving PFS.
  
        Hypothesis: to evaluate the efficacy defined as the PFS rate of lazertinib alone or in
        combination with a cytotoxic anticancer drug in EGFR-mutant NSCLC patients without ctDNA
        clearance after lead-in lazertinib monotherapy.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Progression-free survival
  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 100 months
  description: PFS is measured from the date of start of study to the date of disease progression or death from any cause.
  arm group label: A
  arm group type: Experimental
  description: Lazertinib + chemotherapy combination
  arm group label: B
  arm group type: Active Comparator
  description: Lazertinib monotherapy
  arm group label: C
  arm group type: Active Comparator
  description: Lazertinib monotherapy
  intervention type: Drug
  intervention name: Lazertinib+Pemetrexed+Carboplatin
  description: Arm A will receive Lazertinib and Pemetrexed, Carboplatin combination. Lazertinib will be given 240 mg once a day daily PO until disease progression or unacceptable toxicity. Pemetrexed(500 mg/m2) will be administered IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity. Carboplatin(AUC5) will be administered IV infusions on Day 1 of each 21-day cycle until 4 cycles.
  arm group label: A
  intervention type: Drug
  intervention name: Lazertinib
  description: Lazertinib will be given 240 mg once a day daily PO until disease progression or unacceptable toxicity.
  arm group label: B
  intervention type: Drug
  intervention name: Lazertinib
  description: Lazertinib will be given 240 mg once a day daily PO until disease progression or unacceptable toxicity.
  arm group label: C
  criteria: 
  gender: All
  minimum age: 19 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Sun Min Lim
  role: Principal Investigator
  affiliation: Yonsei University Health System, Severance Hospital
  last name: Sun Min Lim
  phone: +82-2227-8068
  email: limlove2008@yuhs.ac
  facility: 
  contact: 
  country: Korea, Republic of
  responsible party type: Sponsor
  mesh term: Carcinoma, Non-Small-Cell Lung
  mesh term: Carboplatin
  mesh term: Pemetrexed
  mesh term: Lazertinib
  sharing ipd: No