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/NCT05994339</url>
    </required_header>
    <id_info>
      <org_study_id>20220808</org_study_id>
      <nct_id>NCT05994339</nct_id>
    </id_info>
    <brief_title>Radiotherapy Combined With Almonertinib for Stage III EGFR-Mutated Lung Cancer</brief_title>
    <official_title>Radiotherapy Combined With Almonertinib for Stage III EGFR-Mutated Lung Cancer：A Randomized Controlled Clinical Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Laibin People's Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Laibin People's Hospital</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>
        Study Object: Stage III lung cancer with epidermal growth factor receptor (EGFR) sensitive&#xD;
        mutation.&#xD;
  &#xD;
        Study Method: The study subjects will be randomly assigned to the intervention group and the&#xD;
        control group. The intervention group will receive radiotherapy combined with erlotinib&#xD;
        treatment, while the control group will receive concurrent radiotherapy combined with&#xD;
        chemotherapy. The differences in short-term efficacy, long-term efficacy, and incidence of&#xD;
        adverse reactions between the two groups will be observed.&#xD;
  &#xD;
        Observation Indicators: Short-term efficacy indicators: Complete remission (CR) rate, partial&#xD;
        remission (PR) rate, and objective response rate (ORR). Long-term efficacy indicators:&#xD;
        Overall survival (OS) and progression-free survival (PFS). Adverse reaction indicators:&#xD;
        Incidence of lung toxicity, hematological toxicity, and gastrointestinal reactions.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The following tasks need to be completed at the time of enrollment: screening, signing the&#xD;
        informed consent form, random assignment according to the randomization table, detailed&#xD;
        patient medical history, physical examination, and collection of baseline chest-enhanced CT&#xD;
        as imaging data before treatment.&#xD;
  &#xD;
        All eligible patients who meet the baseline inclusion criteria will be enrolled using an&#xD;
        online central randomization system, with the following stratification factors: disease&#xD;
        staging at the beginning of the study treatment (ⅢA vs ⅢB vs ⅢC), histology (adenocarcinoma&#xD;
        vs. others), and EGFR mutation status (exon 19 vs. exon 21). Patients will be randomly&#xD;
        assigned in a 1:1 ratio.&#xD;
  &#xD;
        In the intervention group，Radiotherapy was administered using Intensity-Modulated Radiation&#xD;
        Therapy (IMRT) technique, with a prescribed dose of 60 Gy in 30 fractions. Ametinib was&#xD;
        orally administered at 110 mg per day, starting from the first day of radiotherapy and&#xD;
        continued for 42 days until the completion of radiotherapy, followed by continuous medication&#xD;
        until disease progression. In the control group，Radiotherapy was administered using&#xD;
        Intensity-Modulated Radiation Therapy (IMRT) technique, with a prescribed dose of 60 Gy in 30&#xD;
        fractions. Chemotherapy with paclitaxel at 135 mg/m2 and cisplatin at 70 mg/m2 was&#xD;
        intravenously infused for two cycles during the 1st and 4th weeks. After the completion of&#xD;
        radiotherapy, there was a rest period of 4 weeks, followed by continuation of the TP regimen&#xD;
        for consolidation chemotherapy for 4 cycles.&#xD;
  &#xD;
        Follow-up will take place from August 30, 2023, to December 30, 2025, based on the time of&#xD;
        death. Chest and upper abdominal enhanced CT, cervical supraclavicular lymph node color&#xD;
        Doppler ultrasound, head MRI, whole-body bone scan, and other examinations will be performed&#xD;
        at treatment completion, 1 month after treatment completion, 3 months after treatment&#xD;
        completion, every 3 months within 2 years, and every 6 months in the 3rd year for efficacy&#xD;
        and survival evaluation.&#xD;
  &#xD;
        Statistical Analysis:&#xD;
  &#xD;
        ① Stratified (based on disease stage at the beginning of the study treatment, histology, and&#xD;
        EGFR mutation status) and unstratified log-rank tests will be used to compare&#xD;
        Progression-Free Survival (PFS) and Overall Survival (OS) at a two-sided significance level&#xD;
        of 0.05. The median PFS and corresponding 95% confidence intervals (CI) for both groups will&#xD;
        be calculated.&#xD;
  &#xD;
        ② Cox proportional hazards models will be used to estimate Hazard Ratios (HRs) and 95% CI for&#xD;
        PFS and OS. PFS and OS curves will be estimated using the Kaplan-Meier method.&#xD;
  &#xD;
        ③ Fisher's exact test will be used to compare the difference in Objective Response Rate (ORR)&#xD;
        between the two groups. The difference in ORR and its 95% CI will be presented together using&#xD;
        the normal approximation method.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">December 8, 2025</completion_date>
    <primary_completion_date type="Anticipated">August 8, 2025</primary_completion_date>
    <phase>Phase 2/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>Triple (Participant, Care Provider, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>overall survival(OS)</measure>
      <time_frame>2 years</time_frame>
      <description>the duration from treatment initiation to mortality resulting from any reason.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>progression-free survival (PFS)</measure>
      <time_frame>2 years</time_frame>
      <description>the period from treatment initiation to the first documented progressive disease (PD) or death.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective Response Rate (ORR):</measure>
      <time_frame>3 months</time_frame>
      <description>Complete Remission (CR) is defined as complete disappearance of lesions and maintained for more than 1 month; Partial Remission (PR) is defined as more than 50% reduction in lesion volume and maintained for more than 1 month; Effective rate (ORR) is calculated as CR + PR.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Lung Cancer Stage III</condition>
    <arm_group>
      <arm_group_label>Radiotherapy Combined with Almonertinib</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Radiotherapy was administered using Intensity-Modulated Radiation Therapy (IMRT) technique, with a prescribed dose of 60 Gy in 30 fractions. Almonertinib was orally administered at 110 mg per day, starting from the first day of radiotherapy and continued for 42 days until the completion of radiotherapy, followed by continuous medication until disease progression.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Radiotherapy Combined with Chemotherapy</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Radiotherapy was administered using Intensity-Modulated Radiation Therapy (IMRT) technique, with a prescribed dose of 60 Gy in 30 fractions. Chemotherapy with paclitaxel at 135 mg/m2 and cisplatin at 70 mg/m2 was intravenously infused for two cycles during the 1st and 4th weeks. After the completion of radiotherapy, there was a rest period of 4 weeks, followed by continuation of the TP regimen for consolidation chemotherapy for 4 cycles.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Almonertinib</intervention_name>
      <description>Radiotherapy was administered using Intensity-Modulated Radiation Therapy (IMRT) technique, with a prescribed dose of 60 Gy in 30 fractions. Almonertinib was orally administered at 110 mg per day, starting from the first day of radiotherapy and continued for 42 days until the completion of radiotherapy, followed by continuous medication until disease progression.</description>
      <arm_group_label>Radiotherapy Combined with Almonertinib</arm_group_label>
      <arm_group_label>Radiotherapy Combined with Chemotherapy</arm_group_label>
      <other_name>Intensity-Modulated Radiation Therapy(IMRT)</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients initially diagnosed with lung cancer through imaging and pathological&#xD;
               examination.&#xD;
  &#xD;
                 -  Genetic testing confirms EGFR-sensitive mutations.&#xD;
  &#xD;
                      -  Staging according to the international eighth edition of lung cancer TNM is&#xD;
                         between stage ⅢA to ⅢC.&#xD;
  &#xD;
                           -  Age between 18 to 80 years old, without severe organ diseases such as&#xD;
                              heart, liver, kidney, etc.&#xD;
  &#xD;
                              ⑤ General condition assessed with a performance status (PS) score of ≤2&#xD;
                              points.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  ① Patients with upper gastrointestinal physiological disorders, malabsorption&#xD;
               syndrome, intolerance to oral medications, or peptic ulcers.&#xD;
  &#xD;
                 -  Patients who have received previous radiotherapy or chemotherapy for lung&#xD;
                    conditions.&#xD;
  &#xD;
                      -  Patients with concomitant chronic obstructive pulmonary disease,&#xD;
                         atelectasis, or other conditions that cause difficulties in lesion&#xD;
                         measurements.&#xD;
  &#xD;
                           -  Patients with active pulmonary tuberculosis. ⑤ Patients with&#xD;
                              respiratory failure. ⑥ Patients with allergies to the investigational&#xD;
                              drugs used in this study. ⑦ Pregnant or lactating women. ⑧ Patients&#xD;
                              with any other diseases, neurological or metabolic disorders, physical&#xD;
                              examination or laboratory findings that may raise reasonable suspicions&#xD;
                              of certain diseases or conditions, which would either disqualify the&#xD;
                              use of the investigational drugs or place the subjects at high risk of&#xD;
                              treatment-related complications.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 8, 2023</study_first_submitted>
    <study_first_submitted_qc>August 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 16, 2023</study_first_posted>
    <last_update_submitted>August 28, 2023</last_update_submitted>
    <last_update_submitted_qc>August 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 29, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Laibin People's Hospital</investigator_affiliation>
      <investigator_full_name>Liu Gang</investigator_full_name>
      <investigator_title>Deputy Director of the Department of Oncology</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lung Neoplasms</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/NCT05994339
  org study id: 20220808
  nct id: NCT05994339
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Study Object: Stage III lung cancer with epidermal growth factor receptor (EGFR) sensitive
        mutation.
  
        Study Method: The study subjects will be randomly assigned to the intervention group and the
        control group. The intervention group will receive radiotherapy combined with erlotinib
        treatment, while the control group will receive concurrent radiotherapy combined with
        chemotherapy. The differences in short-term efficacy, long-term efficacy, and incidence of
        adverse reactions between the two groups will be observed.
  
        Observation Indicators: Short-term efficacy indicators: Complete remission (CR) rate, partial
        remission (PR) rate, and objective response rate (ORR). Long-term efficacy indicators:
        Overall survival (OS) and progression-free survival (PFS). Adverse reaction indicators:
        Incidence of lung toxicity, hematological toxicity, and gastrointestinal reactions.
  The following tasks need to be completed at the time of enrollment: screening, signing the
        informed consent form, random assignment according to the randomization table, detailed
        patient medical history, physical examination, and collection of baseline chest-enhanced CT
        as imaging data before treatment.
  
        All eligible patients who meet the baseline inclusion criteria will be enrolled using an
        online central randomization system, with the following stratification factors: disease
        staging at the beginning of the study treatment (ⅢA vs ⅢB vs ⅢC), histology (adenocarcinoma
        vs. others), and EGFR mutation status (exon 19 vs. exon 21). Patients will be randomly
        assigned in a 1:1 ratio.
  
        In the intervention group，Radiotherapy was administered using Intensity-Modulated Radiation
        Therapy (IMRT) technique, with a prescribed dose of 60 Gy in 30 fractions. Ametinib was
        orally administered at 110 mg per day, starting from the first day of radiotherapy and
        continued for 42 days until the completion of radiotherapy, followed by continuous medication
        until disease progression. In the control group，Radiotherapy was administered using
        Intensity-Modulated Radiation Therapy (IMRT) technique, with a prescribed dose of 60 Gy in 30
        fractions. Chemotherapy with paclitaxel at 135 mg/m2 and cisplatin at 70 mg/m2 was
        intravenously infused for two cycles during the 1st and 4th weeks. After the completion of
        radiotherapy, there was a rest period of 4 weeks, followed by continuation of the TP regimen
        for consolidation chemotherapy for 4 cycles.
  
        Follow-up will take place from August 30, 2023, to December 30, 2025, based on the time of
        death. Chest and upper abdominal enhanced CT, cervical supraclavicular lymph node color
        Doppler ultrasound, head MRI, whole-body bone scan, and other examinations will be performed
        at treatment completion, 1 month after treatment completion, 3 months after treatment
        completion, every 3 months within 2 years, and every 6 months in the 3rd year for efficacy
        and survival evaluation.
  
        Statistical Analysis:
  
        ① Stratified (based on disease stage at the beginning of the study treatment, histology, and
        EGFR mutation status) and unstratified log-rank tests will be used to compare
        Progression-Free Survival (PFS) and Overall Survival (OS) at a two-sided significance level
        of 0.05. The median PFS and corresponding 95% confidence intervals (CI) for both groups will
        be calculated.
  
        ② Cox proportional hazards models will be used to estimate Hazard Ratios (HRs) and 95% CI for
        PFS and OS. PFS and OS curves will be estimated using the Kaplan-Meier method.
  
        ③ Fisher's exact test will be used to compare the difference in Objective Response Rate (ORR)
        between the two groups. The difference in ORR and its 95% CI will be presented together using
        the normal approximation method.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Triple (Participant, Care Provider, Investigator)
  measure: overall survival(OS)
  time frame: 2 years
  description: the duration from treatment initiation to mortality resulting from any reason.
  measure: progression-free survival (PFS)
  time frame: 2 years
  description: the period from treatment initiation to the first documented progressive disease (PD) or death.
  measure: Objective Response Rate (ORR):
  time frame: 3 months
  description: Complete Remission (CR) is defined as complete disappearance of lesions and maintained for more than 1 month; Partial Remission (PR) is defined as more than 50% reduction in lesion volume and maintained for more than 1 month; Effective rate (ORR) is calculated as CR + PR.
  arm group label: Radiotherapy Combined with Almonertinib
  arm group type: Experimental
  description: Radiotherapy was administered using Intensity-Modulated Radiation Therapy (IMRT) technique, with a prescribed dose of 60 Gy in 30 fractions. Almonertinib was orally administered at 110 mg per day, starting from the first day of radiotherapy and continued for 42 days until the completion of radiotherapy, followed by continuous medication until disease progression.
  arm group label: Radiotherapy Combined with Chemotherapy
  arm group type: Active Comparator
  description: Radiotherapy was administered using Intensity-Modulated Radiation Therapy (IMRT) technique, with a prescribed dose of 60 Gy in 30 fractions. Chemotherapy with paclitaxel at 135 mg/m2 and cisplatin at 70 mg/m2 was intravenously infused for two cycles during the 1st and 4th weeks. After the completion of radiotherapy, there was a rest period of 4 weeks, followed by continuation of the TP regimen for consolidation chemotherapy for 4 cycles.
  intervention type: Drug
  intervention name: Almonertinib
  description: Radiotherapy was administered using Intensity-Modulated Radiation Therapy (IMRT) technique, with a prescribed dose of 60 Gy in 30 fractions. Almonertinib was orally administered at 110 mg per day, starting from the first day of radiotherapy and continued for 42 days until the completion of radiotherapy, followed by continuous medication until disease progression.
  arm group label: Radiotherapy Combined with Almonertinib
  arm group label: Radiotherapy Combined with Chemotherapy
  other name: Intensity-Modulated Radiation Therapy(IMRT)
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  healthy volunteers: No
  responsible party type: Principal Investigator
  investigator affiliation: Laibin People's Hospital
  investigator full name: Liu Gang
  investigator title: Deputy Director of the Department of Oncology
  mesh term: Lung Neoplasms
  sharing ipd: No