<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/NCT04410796</url>
  </required_header>
  <id_info>
    <org_study_id>20-011</org_study_id>
    <nct_id>NCT04410796</nct_id>
  </id_info>
  <brief_title>Osimertinib Alone or With Chemotherapy for EGFR-Mutant Lung Cancers</brief_title>
  <official_title>A Phase 2 Randomized Study of Osimertinib Versus Osimertinib Plus Chemotherapy for Patients With Metastatic EGFR-Mutant Lung Cancers That Have Detectable EGFR-Mutant cfDNA in Plasma After Initiation of Osimertinib</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Guardant Health, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will compare the effectiveness of osimertinib alone with the combination of&#xD;
      osimertinib and chemotherapy (carboplatin and pemetrexed) in people with metastatic lung&#xD;
      cancer that has a change (mutation) in the gene EGFR. Osimertinib alone is the usual&#xD;
      treatment for metastatic EGFR-mutant lung cancer. Researchers think adding chemotherapy to&#xD;
      osimertinib could possibly add to the anticancer effects of the usual treatment and help stop&#xD;
      cancer from growing or spreading.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Screening portion:&#xD;
&#xD;
      Patients will begin on single agent osimertinib obtained commercially at the standard dose of&#xD;
      80mg orally daily. Osimertinib monotherapy is currently standard of care first-line treatment&#xD;
      for patients with metastatic EGFR-mutant lung cancers. During the screening portion of the&#xD;
      study, patients will be treated per standard practice as decided by the treating physician&#xD;
      using the guidance of the osimertinib product label. The patient will proceed with three&#xD;
      cycles (21 days per cycle) of single agent osimertinib. Patients will be seen on C1D1 for&#xD;
      osimertinib start (telemedicine visits for C1D1 assessments are acceptable)&#xD;
&#xD;
      Randomization/treatment portion:&#xD;
&#xD;
      Patients will be randomized to continue osimertinib alone (Arm A) or addition of&#xD;
      carboplatin/pemetrexed chemotherapy to osimertinib (Arm B).Randomization will be accomplished&#xD;
      by the method of random permuted block and patients will be stratified by type of EGFR&#xD;
      mutation (EGFR exon 19/EGFR L858R or other) and presence of CNS metastases (absent, present).&#xD;
      Randomization will occur after data is available to identify the patients with persistent&#xD;
      EGFR ctDNA detected in the C2D1 plasma sample; only patients with persistent EGFR ctDNA will&#xD;
      be randomized. Subject's eligibility prior to randomization will be at the discretion of the&#xD;
      individual sites enrolling the patients. EGFR mutation can be confirmed at outside&#xD;
      institutions: while pathology confirmation will occur at the enrolling institution, the&#xD;
      required documentation of EGFR can occur internal or external to the enrolling institution.&#xD;
      For those patients without detectable ctDNA at C2D1, the end of treatment assessments will&#xD;
      not include CT scan or ctDNA sampling.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 28, 2020</start_date>
  <completion_date type="Anticipated">May 2024</completion_date>
  <primary_completion_date type="Anticipated">May 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>Crossover Assignment</intervention_model>
    <intervention_model_description>A phase 2 randomized study of osimertinib versus osimertinib plus chemotherapy for patients with metastatic EGFR-mutant lung cancers that have detectable EGFR mutant cfDNA in plasma after initiation of osimertinib treatment.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Determine the progression-free survival</measure>
    <time_frame>2 years</time_frame>
    <description>As the primary endpoint for the treatment comparison, it is the duration of time from randomization to the time of disease progression (in the CNS or systemically) or death. In addition, as a secondary endpoint, PFS is measured from the start of treatment to disease progression or death. Intracranial progression-free survival (PFS) is defined as the duration of time from time of randomization to time of progression (in the CNS) or death, whichever occurs first. Overall survival (OS) is defined as the duration of time from first treatment to time of death.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>overall response rate</measure>
    <time_frame>2 years</time_frame>
    <description>Best overall response rate (confirmed partial and complete responses) will be assessed as part of this study. All responses must be confirmed on subsequent scan to be considered a true response. Tumor response will be assessed using RECIST 1.1. For patients enrolled in the randomized treatment portion of study. Confirmation of baseline measurable disease for all patients will be determined via investigator review.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">571</enrollment>
  <condition>Metastatic Non-small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Osimertinib alone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients will receive osimertinib 80mg orally daily. Subjects randomized to Arm A may be dispensed osimertinib for 2 cycles from Cycle 4 onward.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Osimertinib plus Carboplatin and Pemetrexed</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients will receive osimertinib 80mg orally daily. Patients receive Carboplatin (AUC 5 IV q 3 weeks) and Pemetrexed (500mg/m2 IV q 3 weeks) for a total of 4 cycles followed by pemetrexed maintenance from cycle 8 onwards.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Osimertinib</intervention_name>
    <description>80mg orally daily</description>
    <arm_group_label>Osimertinib alone</arm_group_label>
    <arm_group_label>Osimertinib plus Carboplatin and Pemetrexed</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Carboplatin (AUC 5 IV q 3 weeks)</description>
    <arm_group_label>Osimertinib plus Carboplatin and Pemetrexed</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pemetrexed</intervention_name>
    <description>Pemetrexed (500mg/m2 IV q 3 weeks) for a total of 4 cycles</description>
    <arm_group_label>Osimertinib plus Carboplatin and Pemetrexed</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria: Inital&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Biopsy proven metastatic non-small cell lung cancer, confirmed at enrolling&#xD;
             institution&#xD;
&#xD;
          -  Somatic activating mutation in EGFR in pre-treatment tumor biopsy/ cytology from&#xD;
             pleural fluid or cfDNA&#xD;
&#xD;
          -  Either have not started a prior EGFR TKI therapy or may have started osimertinib&#xD;
             within 3 weeks of confirming eligibility and enrollment criteria of measurable disease&#xD;
             per approval of PI, with no prior chemotherapy for treatment of metastatic disease&#xD;
             (adjuvant therapy &gt; 6 months prior to study start is acceptable)&#xD;
&#xD;
          -  Measurable (RECIST 1.1) indicator lesion not previously irradiated with measurable&#xD;
             disease determined per treating investigator. If a patient has already started on&#xD;
             osimertinib there must be available pre-osimertinib baseline tumor assessments, to be&#xD;
             utilized for RECIST 1.1 assessment.&#xD;
&#xD;
          -  Karnofsky performance status (KPS)≥70%,&#xD;
&#xD;
          -  Ability to swallow oral medications&#xD;
&#xD;
          -  Adequate organ function (use of G-CSF and/or transfusion to meet these criteria are&#xD;
             not allowed)&#xD;
&#xD;
               -  Hemoglobin ≥ 9 g/dL&#xD;
&#xD;
               -  Platelets ≥ 150,000mm^3 or 150 x 10^9/L&#xD;
&#xD;
               -  AST, ALT ≤ 2.5 x ULN with no liver metastases or &lt; 5x ULN with the presence of&#xD;
                  liver metastases&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 x ULN if no liver metastases or &lt; 3 x ULN in the presence&#xD;
                  of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver&#xD;
                  metastases&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1500 cells/mm^3&#xD;
&#xD;
               -  Creatinine ≤ ULN OR calculated creatinine clearance ≥ 60ml/min calculated by&#xD;
                  Cockcroft and Gault equation&#xD;
&#xD;
               -  Creatinine clearance ≥ 60 mL/min calculated by Cockcroft and Gault equation&#xD;
&#xD;
          -  Willing to use highly effective contraceptive measures if of child-bearing potential&#xD;
             or if the patient's sexual partner is a woman of child-bearing potential:&#xD;
&#xD;
               -  Female subjects should be using highly effective contraceptive measures, and must&#xD;
                  have a negative pregnancy test and not be breast-feeding prior to start of dosing&#xD;
                  if of child-bearing potential or must have evidence of non-child-bearing&#xD;
                  potential by fulfilling one of the following criteria at screening:&#xD;
&#xD;
               -  Post-menopausal defined as aged more than 50 years and amenorrheic for at least&#xD;
                  12 months following cessation of all exogenous hormonal treatments&#xD;
&#xD;
               -  Women under 50 years old would be consider postmenopausal if they have been&#xD;
                  amenorrheic for 12 months or more following cessation of exogenous hormonal&#xD;
                  treatments and with LH and FSH levels in the post-menopausal range for the&#xD;
                  institution&#xD;
&#xD;
               -  Documentation of irreversible surgical sterilization by hysterectomy, bilateral&#xD;
                  oophorectomy or bilateral salpingectomy but not tubal ligation&#xD;
&#xD;
               -  Male subjects should be willing to use barrier contraception&#xD;
&#xD;
        Exclusion Criteria: Initial&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Any radiotherapy within 1 week prior to starting treatment on protocol. The washout&#xD;
             window only applies for patients who have not started Osimertinib.&#xD;
&#xD;
          -  Any major surgery within 2 weeks of starting treatment on protocol. The washout window&#xD;
             only applies for patients who have not started Osimertinib.&#xD;
&#xD;
          -  Any evidence of clinically significant interstitial lung disease&#xD;
&#xD;
          -  Treatment with an investigational drug within five half-lives of the compound or 3&#xD;
             months, whichever is greater&#xD;
&#xD;
          -  Currently receiving (or unable to stop prior to receiving the first dose of study&#xD;
             treatment) medications or herbal supplements known to be strong inducers of CYP3A4.&#xD;
             All patients must try to avoid concomitant use of any medications, herbal supplements&#xD;
             and/or ingestion of foods with known inducer effects on CYP3A4.&#xD;
&#xD;
          -  Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of&#xD;
             starting study treatment, with the exception of alopecia and grade 2 prior&#xD;
             platinum-therapy- related neuropathy&#xD;
&#xD;
          -  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&#xD;
&#xD;
          -  active infection including hepatitis B, hepatitis C and human immunodeficiency virus&#xD;
             (HIV). Screening for chronic conditions is not required.&#xD;
&#xD;
          -  Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to&#xD;
             swallow the tablets or previous significant bowel resection that would preclude&#xD;
             adequate absorption of osimertinib.&#xD;
&#xD;
          -  Any of the following cardiac criteria:&#xD;
&#xD;
               -  Mean resting corrected QT interval (QTc) &gt; 470 msec where QT interval is&#xD;
                  corrected for heart rate using Frederica's formula (QTcF).&#xD;
&#xD;
               -  Any clinically important abnormalities in rhythm, conduction or morphology of&#xD;
                  resting ECG e.g. complete left bundle branch block, third degree heart block and&#xD;
                  second degree heart block.&#xD;
&#xD;
               -  Patient with any factors that increase the risk of QTc prolongation or risk of&#xD;
                  arrhythmic events such as heart failure, electrolyte abnormalities (including:&#xD;
                  Serum/Plasma potassium &lt;LLN, Serum/Plasma Magnesium &lt;LLN; Serum/Plasma Calcium&#xD;
                  &lt;LLN), congenital long QT syndrome, family history of long QT syndrome or&#xD;
                  unexplained sudden death under 40 years of age in first degree relatives or any&#xD;
                  concomitant medication known to prolong the QT interval and cause Torsades de&#xD;
                  Pointes&#xD;
&#xD;
          -  Past medical history of interstitial lung disease, drug-induced interstitial lung&#xD;
             disease, radiation pneumonitis which required steroid treatment, or any evidence of&#xD;
             clinically active interstitial lung disease.&#xD;
&#xD;
          -  History of hypersensitivity to active or inactive excipients of osimertinib or drugs&#xD;
             with a similar chemical structure or class to osimertinib.&#xD;
&#xD;
          -  Judgment by the investigator that the patient should not participate in the study if&#xD;
             the patient is unlikely to comply with study procedures, restrictions and&#xD;
             requirements.&#xD;
&#xD;
        Inclusion Criteria: Randomization&#xD;
&#xD;
          -  Patients with detectable plasma EGFR mutations at C2D1&#xD;
&#xD;
          -  Karnofsky performance status (KPS) ≥ 70%&#xD;
&#xD;
          -  Adequate organ function&#xD;
&#xD;
               -  Hemoglobin ≥ 9 g/dL&#xD;
&#xD;
               -  Platelets ≥ 100,000mm^3 or 100 x 10^9/L&#xD;
&#xD;
               -  Creatinine ≤ ULN OR calculated creatinine clearance ≥ 60ml/min&#xD;
&#xD;
               -  AST, ALT ≤ 3x ULN with no liver metastases or ≤ 5x ULN with the presence of liver&#xD;
                  metastases&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 x ULN if no liver metastases or ≤ 3 x ULN in the presence&#xD;
                  of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver&#xD;
                  metastases&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1500 cells/mm3Must have at least stable disease&#xD;
                  per RECIST 1.1 assessment prior to initiating chemotherapy at C4D1&#xD;
&#xD;
               -  Eligibility testing (KPS, bloodwork) should be tested at C3D1. If the subject's&#xD;
                  evaluation does not meet eligibility criteria, any result obtained between C3 and&#xD;
                  C4 can be used&#xD;
&#xD;
        Please note: All 'Initial' Exclusion Criteria must be re-confirmed prior to randomization.&#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>Helena Yu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Helena Yu, MD</last_name>
    <phone>646-608-2252</phone>
    <email>yuh@mskcc.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Gregory Riely, MD, PhD</last_name>
    <phone>646-608-3913</phone>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of California San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Collin Blakely, MD</last_name>
      <phone>415-885-3882</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bruna Pellini, MD</last_name>
      <phone>888-663-3488</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>John Hopkins Medical Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital (Data Collection Only)</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Susan Himes, PhD</last_name>
      <phone>617-726-2000</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)</name>
      <address>
        <city>Basking Ridge</city>
        <state>New Jersey</state>
        <zip>07920</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Helen Yu, MD</last_name>
      <phone>646-608-2252</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hackensack Meridian Health</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kaushal Parikh, MD</last_name>
      <phone>551-996-5087</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Monmouth (Limited Protocol Activities)</name>
      <address>
        <city>Middletown</city>
        <state>New Jersey</state>
        <zip>07748</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Helena Yu, MD</last_name>
      <phone>646-608-2252</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Bergen (Limited Protocol Activities)</name>
      <address>
        <city>Montvale</city>
        <state>New Jersey</state>
        <zip>07645</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Helena Yu, MD</last_name>
      <phone>646-608-2252</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Commack (Limited protocol activities)</name>
      <address>
        <city>Commack</city>
        <state>New York</state>
        <zip>11725</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Helena Yu, MD</last_name>
      <phone>646-608-2252</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Westchester (Limited protocol activities)</name>
      <address>
        <city>Harrison</city>
        <state>New York</state>
        <zip>10604</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Helena Yu, MD</last_name>
      <phone>646-608-2252</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>New York University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10010</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joshua Sabari, MD</last_name>
      <phone>212-731-5662</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center (All protocol activities)</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Helena Yu, MD</last_name>
      <phone>646-608-2252</phone>
    </contact>
    <contact_backup>
      <last_name>Gregory Riely, MD, PhD</last_name>
      <phone>646-608-3913</phone>
    </contact_backup>
    <investigator>
      <last_name>Helena Yu, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Nassau (Limited Protocol Activities)</name>
      <address>
        <city>Uniondale</city>
        <state>New York</state>
        <zip>11553</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Helena Yu, MD</last_name>
      <phone>646-608-2252</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Melissa Johnson, MD</last_name>
      <phone>615-329-7274</phone>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org/mskcc/html/44.cfm</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <last_update_submitted>July 27, 2023</last_update_submitted>
  <last_update_submitted_qc>July 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>EGFR-Mutant Lung Cancers</keyword>
  <keyword>Osimertinib</keyword>
  <keyword>Osimertinib Plus Chemotherapy</keyword>
  <keyword>20-011</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>Carboplatin</mesh_term>
    <mesh_term>Pemetrexed</mesh_term>
    <mesh_term>Osimertinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.</ipd_description>
  </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/NCT04410796
org study id: 20-011
nct id: NCT04410796
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
This study will compare the effectiveness of osimertinib alone with the combination of
      osimertinib and chemotherapy (carboplatin and pemetrexed) in people with metastatic lung
      cancer that has a change (mutation) in the gene EGFR. Osimertinib alone is the usual
      treatment for metastatic EGFR-mutant lung cancer. Researchers think adding chemotherapy to
      osimertinib could possibly add to the anticancer effects of the usual treatment and help stop
      cancer from growing or spreading.
Screening portion:

      Patients will begin on single agent osimertinib obtained commercially at the standard dose of
      80mg orally daily. Osimertinib monotherapy is currently standard of care first-line treatment
      for patients with metastatic EGFR-mutant lung cancers. During the screening portion of the
      study, patients will be treated per standard practice as decided by the treating physician
      using the guidance of the osimertinib product label. The patient will proceed with three
      cycles (21 days per cycle) of single agent osimertinib. Patients will be seen on C1D1 for
      osimertinib start (telemedicine visits for C1D1 assessments are acceptable)

      Randomization/treatment portion:

      Patients will be randomized to continue osimertinib alone (Arm A) or addition of
      carboplatin/pemetrexed chemotherapy to osimertinib (Arm B).Randomization will be accomplished
      by the method of random permuted block and patients will be stratified by type of EGFR
      mutation (EGFR exon 19/EGFR L858R or other) and presence of CNS metastases (absent, present).
      Randomization will occur after data is available to identify the patients with persistent
      EGFR ctDNA detected in the C2D1 plasma sample; only patients with persistent EGFR ctDNA will
      be randomized. Subject's eligibility prior to randomization will be at the discretion of the
      individual sites enrolling the patients. EGFR mutation can be confirmed at outside
      institutions: while pathology confirmation will occur at the enrolling institution, the
      required documentation of EGFR can occur internal or external to the enrolling institution.
      For those patients without detectable ctDNA at C2D1, the end of treatment assessments will
      not include CT scan or ctDNA sampling.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: A phase 2 randomized study of osimertinib versus osimertinib plus chemotherapy for patients with metastatic EGFR-mutant lung cancers that have detectable EGFR mutant cfDNA in plasma after initiation of osimertinib treatment.
primary purpose: Treatment
masking: None (Open Label)
measure: Determine the progression-free survival
time frame: 2 years
description: As the primary endpoint for the treatment comparison, it is the duration of time from randomization to the time of disease progression (in the CNS or systemically) or death. In addition, as a secondary endpoint, PFS is measured from the start of treatment to disease progression or death. Intracranial progression-free survival (PFS) is defined as the duration of time from time of randomization to time of progression (in the CNS) or death, whichever occurs first. Overall survival (OS) is defined as the duration of time from first treatment to time of death.
measure: overall response rate
time frame: 2 years
description: Best overall response rate (confirmed partial and complete responses) will be assessed as part of this study. All responses must be confirmed on subsequent scan to be considered a true response. Tumor response will be assessed using RECIST 1.1. For patients enrolled in the randomized treatment portion of study. Confirmation of baseline measurable disease for all patients will be determined via investigator review.
arm group label: Osimertinib alone
arm group type: Experimental
description: All patients will receive osimertinib 80mg orally daily. Subjects randomized to Arm A may be dispensed osimertinib for 2 cycles from Cycle 4 onward.
arm group label: Osimertinib plus Carboplatin and Pemetrexed
arm group type: Experimental
description: All patients will receive osimertinib 80mg orally daily. Patients receive Carboplatin (AUC 5 IV q 3 weeks) and Pemetrexed (500mg/m2 IV q 3 weeks) for a total of 4 cycles followed by pemetrexed maintenance from cycle 8 onwards.
intervention type: Drug
intervention name: Osimertinib
description: 80mg orally daily
arm group label: Osimertinib alone
arm group label: Osimertinib plus Carboplatin and Pemetrexed
intervention type: Drug
intervention name: Carboplatin
description: Carboplatin (AUC 5 IV q 3 weeks)
arm group label: Osimertinib plus Carboplatin and Pemetrexed
intervention type: Drug
intervention name: Pemetrexed
description: Pemetrexed (500mg/m2 IV q 3 weeks) for a total of 4 cycles
arm group label: Osimertinib plus Carboplatin and Pemetrexed
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Helena Yu, MD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
last name: Helena Yu, MD
phone: 646-608-2252
email: yuh@mskcc.org
last name: Gregory Riely, MD, PhD
phone: 646-608-3913
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country: United States
url: http://www.mskcc.org/mskcc/html/44.cfm
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carboplatin
mesh term: Pemetrexed
mesh term: Osimertinib
sharing ipd: Yes
ipd description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.