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/NCT06018688</url>
    </required_header>
    <id_info>
      <org_study_id>NEWCOAST</org_study_id>
      <nct_id>NCT06018688</nct_id>
    </id_info>
    <brief_title>Osimertinib Combined With Aspirin Neoadjuvant Therapy for Resectable EGFR Mutated NSCLC Patients.</brief_title>
    <official_title>A Phase II Study Evaluating Osimertinib Combined With Aspirin Neoadjuvant Therapy for Resectable EGFR Mutated Non-small Cell Lung Cancer (NSCLC)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Daping Hospital and the Research Institute of Surgery of the Third Military Medical University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Daping Hospital and the Research Institute of Surgery of the Third Military Medical 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>
        This is a single-center, prospective, single-arm, phase II study of Osimertinib combined with&#xD;
        Aspirin neoadjuvant therapy for resectable, EGFR mutated non-small cell lung cancer (NSCLC).&#xD;
        It is mainly aimed at the population of patients with primary IIA- IIIA EGFR sensitive&#xD;
        mutations that are intended to be treated with Osimertinib neoadjuvant therapy.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Lung cancer is currently the leading cause of cancer-related deaths in humans, with its&#xD;
        incidence and mortality rates continuously rising. Among them, non-small cell lung cancer&#xD;
        (NSCLC) accounts for the vast majority of lung cancer cases (approximately 80%). About&#xD;
        one-third of NSCLC cases are early-stage and potentially resectable. Curative surgical&#xD;
        resection is the primary treatment approach for these patients. However, even with curative&#xD;
        surgery, the 5-year survival rate of patients still needs improvement. It has been reported&#xD;
        that approximately 30-55% of early-stage NSCLC patients experience recurrence within 5 years&#xD;
        after surgery, indicating the presence of occult micro-metastases in early NSCLC. Neoadjuvant&#xD;
        therapy before surgery can eliminate micro-metastases, downsize tumors, and reduce the risk&#xD;
        of recurrence, thereby improving patient prognosis and extending survival. Previous studies&#xD;
        have shown that neoadjuvant chemotherapy only achieves a 5% improvement in overall survival&#xD;
        (OS) for patients, and the toxic side effects of chemotherapy limit its broad clinical&#xD;
        application. Therefore, there is an urgent need for better neoadjuvant treatment strategies&#xD;
        to enhance patient survival.&#xD;
  &#xD;
        Research has shown that the epidermal growth factor receptor (EGFR) plays a significant role&#xD;
        in the occurrence and progression of non-small cell lung cancer (NSCLC). For resectable stage&#xD;
        IIA to IIIB NSCLC patients without EGFR mutations, the emergence of neoadjuvant immunotherapy&#xD;
        combined with chemotherapy has been found to significantly prolong the patient's&#xD;
        progression-free survival, improve the pathological complete response rate (pCR), and not&#xD;
        increase the incidence of adverse events, thus providing survival benefits to patients. In&#xD;
        the case of resectable stage IIA to IIIB NSCLC patients with EGFR mutations, several targeted&#xD;
        neoadjuvant treatment attempts using third-generation EGFR-TKIs like osimertinib have been&#xD;
        made, with promising data demonstrating favorable outcomes.&#xD;
  &#xD;
        The 2019 World Conference on Lung Cancer (WCLC) reported a phase II clinical study using&#xD;
        osimertinib as neoadjuvant therapy for patients with EGFR mutant NSCLC. Twenty-seven patients&#xD;
        with stage I-IIIA EGFR mutant NSCLC received 1-2 months of osimertinib as neoadjuvant&#xD;
        treatment prior to surgery. The major pathological response rate (MPR) for 6 assessable&#xD;
        patients was 16%, and the objective response rate (ORR) was 66%. Thirty-three percent of&#xD;
        patients achieved pathological downstaging. In an updated efficacy evaluation of 27 patients&#xD;
        presented at the 2023 American Society of Clinical Oncology (ASCO) meeting, the MPR was 15%,&#xD;
        ORR was 48%, R0 resection rate was 89%, median disease-free survival (mDFS) was 32.4 months,&#xD;
        and median overall survival (mOS) was not reached. Another real-world retrospective study&#xD;
        presented at the 2021 WCLC also explored the efficacy and safety of osimertinib in&#xD;
        neoadjuvant therapy for stage I-IIIB patients. Seventeen patients who received osimertinib as&#xD;
        neoadjuvant treatment had an MPR of 23.5%, pathological complete response (pCR) rate of 5.9%,&#xD;
        and ORR of 88.2%. Overall, the treatment was well-tolerated. The mid-term results of the NEOS&#xD;
        study presented at the 2021 ASCO Annual Meeting further confirmed the benefits of osimertinib&#xD;
        as neoadjuvant therapy, although the data is still immature. From October 17, 2018, to June&#xD;
        8, 2021, a total of 88 patients were screened, and 40 patients were ultimately enrolled.&#xD;
        Among the 38 patients who completed 6 weeks of osimertinib neoadjuvant therapy, the ORR was&#xD;
        71.1% , and the disease control rate reached 100%. This indicates that no disease progression&#xD;
        occurred during the neoadjuvant treatment, and 71.1% of patients had significant tumor&#xD;
        shrinkage, creating an opportunity to reduce the extent of surgical resection, decrease the&#xD;
        difficulty of surgery, and improve surgical outcomes. However, among the 28 patients with&#xD;
        assessable pathology, only 11% achieved MPR, and only 1 patient (4%) achieved pCR. It is well&#xD;
        known that pathological response rates are closely related to postoperative recurrence and&#xD;
        survival time. It would be clinically significant to further enhance the pathological&#xD;
        response rate of osimertinib neoadjuvant patients through combination therapy strategies,&#xD;
        which could reduce postoperative recurrence rates and improve overall survival.&#xD;
  &#xD;
        Aspirin, a classic drug known for its antiplatelet effects, exhibits safety, affordability,&#xD;
        and easy accessibility. Its potential role in cancer treatment has been widely explored.&#xD;
        Recent studies have demonstrated the following:1. Women who take aspirin at least three times&#xD;
        a week have a 16% reduced risk of developing breast cancer.2. Aspirin enhances the efficacy&#xD;
        of the anti-tumor drug sorafenib in mouse models of lung cancer and melanoma with RAS gene&#xD;
        mutations.3. By binding to the key amino acid Glu225, aspirin inhibits enzymatic activity of&#xD;
        acetylheparinase, thereby suppressing tumor angiogenesis and metastasis.4. Aspirin boosts the&#xD;
        effectiveness of T-cell therapy and enhances the body's immune response against cancer.5.&#xD;
        Aspirin has received FDA approval for its preventive use in colorectal cancer.Numerous&#xD;
        clinical and basic trials have validated the role of aspirin in cancer prevention and&#xD;
        treatment. Moreover, our earlier research indicated that aspirin improves the&#xD;
        immunosuppressive microenvironment associated with osimertinib, activates cytotoxic T-cell&#xD;
        function, and enhances the killing ability of T cells against tumor cells, ultimately&#xD;
        promoting tumor cell apoptosis. Lung cancer patients inherently experience a hypercoagulable&#xD;
        state and are prone to critical cardiovascular events. Regular low-dose aspirin usage reduces&#xD;
        the incidence of coronary events in lung cancer patients. Therefore, if further evidence&#xD;
        confirms aspirin's ability to overcome osimertinib resistance beyond its antiplatelet&#xD;
        effects, combining osimertinib with aspirin in neoadjuvant therapy for NSCLC patients could&#xD;
        potentially enhance pathological response, reduce postoperative recurrence, and further&#xD;
        improve the overall prognosis of patients eligible for surgical intervention.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 15, 2023</start_date>
    <completion_date type="Anticipated">September 1, 2026</completion_date>
    <primary_completion_date type="Anticipated">March 1, 2026</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Major pathologic response</measure>
      <time_frame>At Surgery approximately 4weeks after last treatment</time_frame>
      <description>MPR refers to the percentage of residual viable tumor cells within the tumor bed after neoadjuvant treatment, with a threshold of ≤10%, regardless of the presence of residual viable tumor cells in the lymph nodes.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Disease 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 60 months.</time_frame>
      <description>DFS was defined as the time from complete surgical resection to recurrence or death due to any reason.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective Response Rate</measure>
      <time_frame>At Surgery approximately 4weeks after last treatment</time_frame>
      <description>Objective response rate (ORR) refers to the proportion of patients in a clinical trial or treatment setting whose tumor size reduces or disappears (partial or complete response) in response to the therapy being administered.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease Control Rate</measure>
      <time_frame>At Surgery approximately 4weeks after last treatment</time_frame>
      <description>Disease control rate (DCR) describes the percentage of patients with advanced cancer whose therapeutic intervention has led to a complete response, partial response, or stable disease.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pathologic complete response</measure>
      <time_frame>At Surgery approximately 4weeks after last treatment</time_frame>
      <description>PCR refers to the absence of residual viable tumor cells in the tumor bed and lymph nodes after neoadjuvant therapy.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">44</enrollment>
    <condition>Non Small Cell Lung Cancer</condition>
    <condition>EGFR Gene Mutation</condition>
    <arm_group>
      <arm_group_label>osimertinib and aspirin</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Osimertinib and Aspirin starting at a dose of 80 mg and 100mg once a day, orally with meals.The participants will undergo a two-month combination therapy, unless there is tumor progression (worsening) or intolerable toxic reactions that necessitate early termination of the drug treatment. Aspirin will be discontinued one week prior to the surgery.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Osimertinib</intervention_name>
      <description>Osimertinib is a 3rd-generation EGFR-TKI used to treat NSCLC patients with resistance to 1st generation EGFR-TKI due to T790M mutation. It has been approved in clinical applications by the FDA in 2015.</description>
      <arm_group_label>osimertinib and aspirin</arm_group_label>
      <other_name>OSI</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Aspirin</intervention_name>
      <description>Aspirin, also known as acetylsalicylic acid (ASA), is a verysafe medication used to treat pain,fever, or inflammation.</description>
      <arm_group_label>osimertinib and aspirin</arm_group_label>
      <other_name>ASP</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Patients with resectable stage IIA-IIIA lung adenocarcinoma.&#xD;
  &#xD;
            2. Patients with EGFR sensitizing mutations (Ex19del or L858R).&#xD;
  &#xD;
            3. Intended neoadjuvant therapy with osimertinib, with an anticipated survival expectancy&#xD;
               of more than 3 months.&#xD;
  &#xD;
            4. ECOG PS 0/1.&#xD;
  &#xD;
            5. Primary lesion diameter of at least 1 cm.&#xD;
  &#xD;
            6. Patients who have previously taken or are currently taking aspirin therapy are&#xD;
               allowed.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Currently receiving other anticoagulant therapy.&#xD;
  &#xD;
            2. Previously treated with systemic therapy for NSCLC.&#xD;
  &#xD;
            3. Other positive driver mutations, including ALK, ROS1, MET14 exon skipping, BRAF, RET,&#xD;
               etc.&#xD;
  &#xD;
            4. Contraindications to the use of osimertinib and aspirin.&#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>He yong</last_name>
      <phone>86-23-68757791</phone>
      <email>heyong8998@126.com</email>
    </overall_contact>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 4, 2023</study_first_submitted>
    <study_first_submitted_qc>August 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 31, 2023</study_first_posted>
    <last_update_submitted>September 15, 2023</last_update_submitted>
    <last_update_submitted_qc>September 15, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Daping Hospital and the Research Institute of Surgery of the Third Military Medical University</investigator_affiliation>
      <investigator_full_name>Yong He</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <keyword>Non-Small Cell Lung Cancer</keyword>
    <keyword>Aspirin</keyword>
    <keyword>Osimertinib</keyword>
    <keyword>EGFR-TKI</keyword>
    <keyword>neoadjuvant therapy</keyword>
    <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>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Aspirin</mesh_term>
      <mesh_term>Osimertinib</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Undecided</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/NCT06018688
  org study id: NEWCOAST
  nct id: NCT06018688
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  This is a single-center, prospective, single-arm, phase II study of Osimertinib combined with
        Aspirin neoadjuvant therapy for resectable, EGFR mutated non-small cell lung cancer (NSCLC).
        It is mainly aimed at the population of patients with primary IIA- IIIA EGFR sensitive
        mutations that are intended to be treated with Osimertinib neoadjuvant therapy.
  Lung cancer is currently the leading cause of cancer-related deaths in humans, with its
        incidence and mortality rates continuously rising. Among them, non-small cell lung cancer
        (NSCLC) accounts for the vast majority of lung cancer cases (approximately 80%). About
        one-third of NSCLC cases are early-stage and potentially resectable. Curative surgical
        resection is the primary treatment approach for these patients. However, even with curative
        surgery, the 5-year survival rate of patients still needs improvement. It has been reported
        that approximately 30-55% of early-stage NSCLC patients experience recurrence within 5 years
        after surgery, indicating the presence of occult micro-metastases in early NSCLC. Neoadjuvant
        therapy before surgery can eliminate micro-metastases, downsize tumors, and reduce the risk
        of recurrence, thereby improving patient prognosis and extending survival. Previous studies
        have shown that neoadjuvant chemotherapy only achieves a 5% improvement in overall survival
        (OS) for patients, and the toxic side effects of chemotherapy limit its broad clinical
        application. Therefore, there is an urgent need for better neoadjuvant treatment strategies
        to enhance patient survival.
  
        Research has shown that the epidermal growth factor receptor (EGFR) plays a significant role
        in the occurrence and progression of non-small cell lung cancer (NSCLC). For resectable stage
        IIA to IIIB NSCLC patients without EGFR mutations, the emergence of neoadjuvant immunotherapy
        combined with chemotherapy has been found to significantly prolong the patient's
        progression-free survival, improve the pathological complete response rate (pCR), and not
        increase the incidence of adverse events, thus providing survival benefits to patients. In
        the case of resectable stage IIA to IIIB NSCLC patients with EGFR mutations, several targeted
        neoadjuvant treatment attempts using third-generation EGFR-TKIs like osimertinib have been
        made, with promising data demonstrating favorable outcomes.
  
        The 2019 World Conference on Lung Cancer (WCLC) reported a phase II clinical study using
        osimertinib as neoadjuvant therapy for patients with EGFR mutant NSCLC. Twenty-seven patients
        with stage I-IIIA EGFR mutant NSCLC received 1-2 months of osimertinib as neoadjuvant
        treatment prior to surgery. The major pathological response rate (MPR) for 6 assessable
        patients was 16%, and the objective response rate (ORR) was 66%. Thirty-three percent of
        patients achieved pathological downstaging. In an updated efficacy evaluation of 27 patients
        presented at the 2023 American Society of Clinical Oncology (ASCO) meeting, the MPR was 15%,
        ORR was 48%, R0 resection rate was 89%, median disease-free survival (mDFS) was 32.4 months,
        and median overall survival (mOS) was not reached. Another real-world retrospective study
        presented at the 2021 WCLC also explored the efficacy and safety of osimertinib in
        neoadjuvant therapy for stage I-IIIB patients. Seventeen patients who received osimertinib as
        neoadjuvant treatment had an MPR of 23.5%, pathological complete response (pCR) rate of 5.9%,
        and ORR of 88.2%. Overall, the treatment was well-tolerated. The mid-term results of the NEOS
        study presented at the 2021 ASCO Annual Meeting further confirmed the benefits of osimertinib
        as neoadjuvant therapy, although the data is still immature. From October 17, 2018, to June
        8, 2021, a total of 88 patients were screened, and 40 patients were ultimately enrolled.
        Among the 38 patients who completed 6 weeks of osimertinib neoadjuvant therapy, the ORR was
        71.1% , and the disease control rate reached 100%. This indicates that no disease progression
        occurred during the neoadjuvant treatment, and 71.1% of patients had significant tumor
        shrinkage, creating an opportunity to reduce the extent of surgical resection, decrease the
        difficulty of surgery, and improve surgical outcomes. However, among the 28 patients with
        assessable pathology, only 11% achieved MPR, and only 1 patient (4%) achieved pCR. It is well
        known that pathological response rates are closely related to postoperative recurrence and
        survival time. It would be clinically significant to further enhance the pathological
        response rate of osimertinib neoadjuvant patients through combination therapy strategies,
        which could reduce postoperative recurrence rates and improve overall survival.
  
        Aspirin, a classic drug known for its antiplatelet effects, exhibits safety, affordability,
        and easy accessibility. Its potential role in cancer treatment has been widely explored.
        Recent studies have demonstrated the following:1. Women who take aspirin at least three times
        a week have a 16% reduced risk of developing breast cancer.2. Aspirin enhances the efficacy
        of the anti-tumor drug sorafenib in mouse models of lung cancer and melanoma with RAS gene
        mutations.3. By binding to the key amino acid Glu225, aspirin inhibits enzymatic activity of
        acetylheparinase, thereby suppressing tumor angiogenesis and metastasis.4. Aspirin boosts the
        effectiveness of T-cell therapy and enhances the body's immune response against cancer.5.
        Aspirin has received FDA approval for its preventive use in colorectal cancer.Numerous
        clinical and basic trials have validated the role of aspirin in cancer prevention and
        treatment. Moreover, our earlier research indicated that aspirin improves the
        immunosuppressive microenvironment associated with osimertinib, activates cytotoxic T-cell
        function, and enhances the killing ability of T cells against tumor cells, ultimately
        promoting tumor cell apoptosis. Lung cancer patients inherently experience a hypercoagulable
        state and are prone to critical cardiovascular events. Regular low-dose aspirin usage reduces
        the incidence of coronary events in lung cancer patients. Therefore, if further evidence
        confirms aspirin's ability to overcome osimertinib resistance beyond its antiplatelet
        effects, combining osimertinib with aspirin in neoadjuvant therapy for NSCLC patients could
        potentially enhance pathological response, reduce postoperative recurrence, and further
        improve the overall prognosis of patients eligible for surgical intervention.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Major pathologic response
  time frame: At Surgery approximately 4weeks after last treatment
  description: MPR refers to the percentage of residual viable tumor cells within the tumor bed after neoadjuvant treatment, with a threshold of ≤10%, regardless of the presence of residual viable tumor cells in the lymph nodes.
  measure: Disease 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 60 months.
  description: DFS was defined as the time from complete surgical resection to recurrence or death due to any reason.
  measure: Objective Response Rate
  time frame: At Surgery approximately 4weeks after last treatment
  description: Objective response rate (ORR) refers to the proportion of patients in a clinical trial or treatment setting whose tumor size reduces or disappears (partial or complete response) in response to the therapy being administered.
  measure: Disease Control Rate
  time frame: At Surgery approximately 4weeks after last treatment
  description: Disease control rate (DCR) describes the percentage of patients with advanced cancer whose therapeutic intervention has led to a complete response, partial response, or stable disease.
  measure: Pathologic complete response
  time frame: At Surgery approximately 4weeks after last treatment
  description: PCR refers to the absence of residual viable tumor cells in the tumor bed and lymph nodes after neoadjuvant therapy.
  arm group label: osimertinib and aspirin
  arm group type: Experimental
  description: Osimertinib and Aspirin starting at a dose of 80 mg and 100mg once a day, orally with meals.The participants will undergo a two-month combination therapy, unless there is tumor progression (worsening) or intolerable toxic reactions that necessitate early termination of the drug treatment. Aspirin will be discontinued one week prior to the surgery.
  intervention type: Drug
  intervention name: Osimertinib
  description: Osimertinib is a 3rd-generation EGFR-TKI used to treat NSCLC patients with resistance to 1st generation EGFR-TKI due to T790M mutation. It has been approved in clinical applications by the FDA in 2015.
  arm group label: osimertinib and aspirin
  other name: OSI
  intervention type: Drug
  intervention name: Aspirin
  description: Aspirin, also known as acetylsalicylic acid (ASA), is a verysafe medication used to treat pain,fever, or inflammation.
  arm group label: osimertinib and aspirin
  other name: ASP
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: He yong
  phone: 86-23-68757791
  email: heyong8998@126.com
  responsible party type: Principal Investigator
  investigator affiliation: Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
  investigator full name: Yong He
  investigator title: Professor
  mesh term: Lung Neoplasms
  mesh term: Carcinoma, Non-Small-Cell Lung
  mesh term: Aspirin
  mesh term: Osimertinib
  sharing ipd: Undecided