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/NCT06031688</url>
    </required_header>
    <id_info>
      <org_study_id>S1900K</org_study_id>
      <secondary_id>NCI-2023-04727</secondary_id>
      <secondary_id>S1900K</secondary_id>
      <secondary_id>S1900K</secondary_id>
      <secondary_id>U10CA180888</secondary_id>
      <nct_id>NCT06031688</nct_id>
    </id_info>
    <brief_title>Targeted Treatment for Advanced Non-Small Cell Lung Cancer That Has a MET Exon 14 Skipping Gene Change (An Expanded Lung-MAP Treatment Trial)</brief_title>
    <official_title>A Randomized Phase II Study of Tepotinib With or Without Ramucirumab in Participants With MET Exon 14 Skipping Positive Stage IV or Recurrent Non-Small Cell Lung Cancer (LUNG-MAP SUB-STUDY)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>SWOG Cancer Research Network</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Cancer Institute (NCI)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>SWOG Cancer Research Network</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This phase II Expanded Lung-MAP treatment trial tests tepotinib with or without ramucirumab&#xD;
        for the treatment of patients with advanced non-small cell lung cancer that has spread from&#xD;
        where it first started (primary site) to other places in the body (stage IV) or that has come&#xD;
        back after a period of improvement (recurrent). Tepotinib is used in patients whose cancer&#xD;
        has a mutated (changed) form of a gene called MET. It is in a class of medications called&#xD;
        kinase inhibitors. It works by blocking the action of the abnormal MET protein that signals&#xD;
        tumor cells to multiply. This helps slow or stop the spread of tumor cells. Ramucirumab is a&#xD;
        monoclonal antibody that may prevent the growth of new blood vessels that tumors need to&#xD;
        grow. Giving tepotinib with ramucirumab may lower the chance of the cancer from growing or&#xD;
        spreading in patients with stage IV or recurrent non-small cell lung cancer.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        PRIMARY OBJECTIVE:&#xD;
  &#xD;
        I. To compare the response rate (confirmed or unconfirmed, complete or impartial) between&#xD;
        participants with MET exon 14 skipping positive non-small cell lung cancer (NSCLC) randomized&#xD;
        to tepotinib with or without ramucirumab.&#xD;
  &#xD;
        SECONDARY OBJECTIVES:&#xD;
  &#xD;
        I. To compare the frequency of all-grade treatment- related peripheral edema as defined by&#xD;
        Common Terminology Criteria for Adverse Events (CTCAE) between the arms.&#xD;
  &#xD;
        II. To evaluate the frequency and severity of toxicities within each arm. III. To compare&#xD;
        progression-free survival between the arms. IV. To compare overall survival between the arms.&#xD;
        V. To estimate the duration of response (DoR) among responders within each arm.&#xD;
  &#xD;
        TRANSLATIONAL MEDICINE OBJECTIVE:&#xD;
  &#xD;
        I. To establish a tissue/blood repository for participants with MET exon 14 skipping&#xD;
        non-small cell lung cancer (NSCLC).&#xD;
  &#xD;
        OUTLINE: Patients are randomized to 1 of 2 arms.&#xD;
  &#xD;
        ARM A: Patients receive ramucirumab intravenously (IV) over 30-60 minutes on day 1 of each&#xD;
        cycle and tepotinib orally (PO) once daily (QD) on days 1-21 of each cycle. Cycles repeat&#xD;
        every 21 days in the absence of disease progression or unacceptable toxicity.&#xD;
  &#xD;
        ARM B: Patients receive tepotinib PO QD on days 1-21 of each cycle. Cycles repeat every 21&#xD;
        days in the absence of disease progression or unacceptable toxicity.&#xD;
  &#xD;
        Patients undergo lymphoscintigraphy scan and computed tomography (CT) scan and/or magnetic&#xD;
        resonance imaging (MRI) throughout the trial. Patients also undergo blood sample collection&#xD;
        while on study.&#xD;
  &#xD;
        After completion of study treatment, patients are followed-up every 12 weeks or more often as&#xD;
        clinically indicated until progression and then every 6 months for 2 years and at the end of&#xD;
        3 years from date of sub-study randomization.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 6, 2024</start_date>
    <completion_date type="Anticipated">May 31, 2029</completion_date>
    <primary_completion_date type="Anticipated">May 31, 2028</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>Response rate</measure>
      <time_frame>Up to 3 years from date of sub-study randomization</time_frame>
      <description>Rates will be compared using a chi-squared test at the 1-sided 10% level and also presented as the difference in response rates with the associated 80% confidence interval for the difference, Further, response rates and associated 80% confidence interval will be estimated for each arm.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Frequency of treatment-related peripheral edema</measure>
      <time_frame>Up to 3 years from date of sub-study randomization</time_frame>
      <description>The frequency of peripheral edema will be compared using a 2-sided 10% level test of proportions. All-grade peripheral edema will be estimated along with 90% confidence intervals. Data from lymphoscintigraphy imaging will be summarized for baseline and among those with peripheral edema.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v5.0</measure>
      <time_frame>Up to 3 years from date of sub-study randomization</time_frame>
      <description>The number of participants with treatment-related adverse events as assessed by CTCAE v5.0 within each treatment arm will be evaluated.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival</measure>
      <time_frame>From date of sub-study randomization to date of first documentation of progression or death due to any cause, assessed up to 3 years</time_frame>
      <description>Will be estimated using the method of Kaplan-Meier. Will be compared between the arms using a 1-sided 10% level log-rank test. Medians and associated 80% confidence intervals will be estimated using the Brookmeyer-Crowley method.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>Up to 3 years from date of sub-study randomization</time_frame>
      <description>Will be estimated using the method of Kaplan-Meier. Medians and associated 80% confidence intervals will be estimated using the Brookmeyer-Crowley method.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of response</measure>
      <time_frame>From date of first documentation of response (complete response [CR] or partial response [PR]) to date of first documentation of progression or death due to any cause among participants who achieve a response (CR or PR), assessed up to 3 years</time_frame>
      <description>Will be estimated using the method of Kaplan-Meier. Medians and associated 80% confidence intervals will be estimated using the Brookmeyer-Crowley method.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">56</enrollment>
    <condition>Recurrent Lung Non-Small Cell Carcinoma</condition>
    <condition>Stage IV Lung Cancer AJCC v8</condition>
    <arm_group>
      <arm_group_label>Arm A: (Ramucirumab and tepotinib)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients receive ramucirumab IV over 30-60 minutes on day 1 of each cycle and tepotinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo lymphoscintigraphy scan and CT scan and/or MRI throughout the trial. Patients also undergo blood sample collection while on study.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm B: (Tepotinib)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Patients receive tepotinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo lymphoscintigraphy scan and CT scan and/or MRI throughout the trial. Patients also undergo blood sample collection while on study.</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Biospecimen Collection</intervention_name>
      <description>Undergo blood sample collection</description>
      <arm_group_label>Arm A: (Ramucirumab and tepotinib)</arm_group_label>
      <arm_group_label>Arm B: (Tepotinib)</arm_group_label>
      <other_name>Biological Sample Collection</other_name>
      <other_name>Biospecimen Collected</other_name>
      <other_name>Specimen Collection</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Computed Tomography</intervention_name>
      <description>Undergo CT scan</description>
      <arm_group_label>Arm A: (Ramucirumab and tepotinib)</arm_group_label>
      <arm_group_label>Arm B: (Tepotinib)</arm_group_label>
      <other_name>CAT</other_name>
      <other_name>CAT Scan</other_name>
      <other_name>Computed Axial Tomography</other_name>
      <other_name>Computerized Axial Tomography</other_name>
      <other_name>Computerized axial tomography (procedure)</other_name>
      <other_name>Computerized Tomography</other_name>
      <other_name>CT</other_name>
      <other_name>CT Scan</other_name>
      <other_name>tomography</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Lymphoscintigraphy</intervention_name>
      <description>Undergo lymphoscintigraphy scan</description>
      <arm_group_label>Arm A: (Ramucirumab and tepotinib)</arm_group_label>
      <arm_group_label>Arm B: (Tepotinib)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Magnetic Resonance Imaging</intervention_name>
      <description>Undergo MRI</description>
      <arm_group_label>Arm A: (Ramucirumab and tepotinib)</arm_group_label>
      <arm_group_label>Arm B: (Tepotinib)</arm_group_label>
      <other_name>Magnetic Resonance</other_name>
      <other_name>Magnetic resonance imaging (procedure)</other_name>
      <other_name>Magnetic Resonance Imaging Scan</other_name>
      <other_name>Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance</other_name>
      <other_name>MR</other_name>
      <other_name>MR Imaging</other_name>
      <other_name>MRI</other_name>
      <other_name>MRI Scan</other_name>
      <other_name>NMR Imaging</other_name>
      <other_name>NMRI</other_name>
      <other_name>Nuclear Magnetic Resonance Imaging</other_name>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Ramucirumab</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Arm A: (Ramucirumab and tepotinib)</arm_group_label>
      <other_name>Anti-VEGFR-2 Fully Human Monoclonal Antibody IMC-1121B</other_name>
      <other_name>Cyramza</other_name>
      <other_name>IMC-1121B</other_name>
      <other_name>LY3009806</other_name>
      <other_name>Monoclonal Antibody HGS-ETR2</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tepotinib</intervention_name>
      <description>Given PO</description>
      <arm_group_label>Arm A: (Ramucirumab and tepotinib)</arm_group_label>
      <arm_group_label>Arm B: (Tepotinib)</arm_group_label>
      <other_name>c-Met Inhibitor MSC2156119J</other_name>
      <other_name>EMD 1214063</other_name>
      <other_name>EMD-1214063</other_name>
      <other_name>EMD1214063</other_name>
      <other_name>MSC2156119J</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Participants must have been assigned to S1900K by the Southwest Oncology Group (SWOG)&#xD;
               Statistics and Data Management Center (SDMC). Assignment to S1900K is determined by&#xD;
               the LUNGMAP protocol&#xD;
  &#xD;
            -  Participants must have documentation of NSCLC with a MET exon 14 skipping mutation&#xD;
               determined by tissue-based or blood-based (circulating tumor DNA [ctDNA]) next&#xD;
               generation sequencing (NGS) assay done within a laboratory with Clinical Laboratory&#xD;
               Improvement Act (CLIA), International Organization for Standardization (ISO)/&#xD;
               International Electrotechnical Commission (IEC), College of American Pathologists&#xD;
               (CAP), or similar certification. Documentation must either be:&#xD;
  &#xD;
                 -  NGS test results from tissue submitted for LUNGMAP screening, or&#xD;
  &#xD;
                 -  Submitted documentation in the LUNGMAP Rave Electronic Data Capture System of a&#xD;
                    MET exon 14 skipping mutation from a previously completed tissue or blood-based&#xD;
                    NGS test NOTE: Participants previously tested for and determined to have a MET&#xD;
                    exon 14 skipping mutation, outside of LUNGMAP, must also submit tissue for&#xD;
                    central Foundation Medicine (FMI) testing on the LUNGMAP screening protocol, if&#xD;
                    available&#xD;
  &#xD;
            -  Participants must have measurable disease documented by CT or MRI. The CT from a&#xD;
               combined positron emission tomography (PET)/CT may be used to document measurable&#xD;
               disease ONLY if it is of diagnostic quality, otherwise, it may be used to document&#xD;
               non-measurable disease only. Measurable disease must be assessed within 28 days prior&#xD;
               to sub-study randomization. Pleural effusions, ascites and laboratory parameters are&#xD;
               not acceptable as the only evidence of disease. Non-measurable disease must be&#xD;
               assessed within 42 days prior to sub-study randomization. All known sites of disease&#xD;
               must be assessed and documented on the Baseline Tumor Assessment Form. Participants&#xD;
               whose only measurable disease is within a previous radiation therapy port must&#xD;
               demonstrate clearly progressive disease (in the opinion of the treating investigator)&#xD;
               prior to sub-study randomization to be considered measurable&#xD;
  &#xD;
            -  Participants must have a CT or MRI scan of the brain to evaluate for central nervous&#xD;
               system (CNS) disease within 42 days prior to sub-study randomization&#xD;
  &#xD;
            -  Participants must not have leptomeningeal disease, spinal cord compression or brain&#xD;
               metastases unless:&#xD;
  &#xD;
                 -  Metastases have been locally treated and have remained clinically controlled and&#xD;
                    asymptomatic for at least 3 days following the stereotactic radiation and/or 14&#xD;
                    days following whole brain radiation, and prior to sub-study randomization, AND&#xD;
  &#xD;
                 -  Participant has no residual neurological dysfunction and has been off&#xD;
                    corticosteroids for at least 24 hours prior to sub-study randomization&#xD;
  &#xD;
            -  Participants must not have other known actionable oncogenic alterations, such as (but&#xD;
               not limited to) EGFR sensitizing mutations, EGFR T790M mutation, ALK gene fusion, ROS1&#xD;
               gene rearrangement, RET gene rearrangement, NTRK rearrangement, HER2 mutation, KRAS&#xD;
               activating mutations, and BRAF V600E mutation&#xD;
  &#xD;
            -  Participants must have progressed (in the opinion of the treating physician) following&#xD;
               the most recent line of therapy&#xD;
  &#xD;
            -  Participants must have received at least one line of systemic treatment for Stage IV&#xD;
               or recurrent NSCLC&#xD;
  &#xD;
            -  Participants must have recovered (=&lt; grade 1) from any side effects of prior therapy&#xD;
               except alopecia and vitiligo&#xD;
  &#xD;
            -  Participants must not have received any prior systemic therapy (systemic chemotherapy,&#xD;
               immunotherapy or investigational drug) within 21 days prior to sub-study randomization&#xD;
  &#xD;
            -  Participants must not have received treatment with prior MET inhibitor therapies&#xD;
               (e.g., crizotinib, tivantinib, savolitinib, tepotinib, cabozantinib, and foretinib).&#xD;
  &#xD;
            -  Participants must not have received treatment with prior angiogenesis inhibitor&#xD;
               therapies (including but not limited to bevacizumab and ramucirumab)&#xD;
  &#xD;
            -  Participants must not have a history of interstitial lung disease that required&#xD;
               steroid treatment&#xD;
  &#xD;
            -  Participants must not have received any radiation therapy within 7 days prior to&#xD;
               sub-study randomization with the exceptions of&#xD;
  &#xD;
                 -  Stereotactic radiation to CNS metastases which must have been completed at least&#xD;
                    3 days prior to sub-study randomization and&#xD;
  &#xD;
                 -  Palliative radiotherapy to bone metastases which must have been completed at&#xD;
                    least 1 day prior to sub-study randomization&#xD;
  &#xD;
            -  Participants must not be planning to receive any concurrent chemotherapy,&#xD;
               immunotherapy, biologic or hormonal therapy for cancer treatment while receiving&#xD;
               treatment on this study&#xD;
  &#xD;
            -  Participants must not have had a major surgery within 14 days prior to sub-study&#xD;
               randomization. Participants must have fully recovered from the effects of prior&#xD;
               surgery in the opinion of the treating investigator&#xD;
  &#xD;
            -  Participants must not have a prior or concurrent malignancy whose natural history or&#xD;
               treatment (in the opinion of the treating physician) has the potential to interfere&#xD;
               with the safety or efficacy assessment of the investigational regimen&#xD;
  &#xD;
            -  Participants must be able to swallow tablets whole&#xD;
  &#xD;
            -  Absolute neutrophil count &gt;= 1.5 x 10^3/uL (within 28 days prior to sub-study&#xD;
               randomization)&#xD;
  &#xD;
            -  Hemoglobin &gt;= 9.0 g/dL (within 28 days prior to sub-study randomization)&#xD;
  &#xD;
            -  Platelets &gt;= 100 x 10^3/uL (within 28 days prior to sub-study randomization)&#xD;
  &#xD;
            -  Total bilirubin =&lt; 1.5 x institutional upper limit of normal (ULN) unless history of&#xD;
               Gilbert's disease. Participants with history of Gilbert's disease must have total&#xD;
               bilirubin =&lt; 5 x institutional ULN (within 28 days prior to sub-study randomization)&#xD;
  &#xD;
            -  Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) =&lt; 2.5 ×&#xD;
               institutional ULN. Participants with history of liver metastasis must have AST =&lt; 5 x&#xD;
               ULN (within 28 days prior to sub-study randomization)&#xD;
  &#xD;
            -  Participants must have a serum creatinine =&lt; the institutional upper limit of normal&#xD;
               (IULN) or calculated creatinine clearance &gt;= 30 mL/min using the following&#xD;
               Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28&#xD;
               days prior to sub-study randomization&#xD;
  &#xD;
            -  Participants must have a cystatin C test performed to obtain baseline value within 28&#xD;
               days prior to sub-study randomization&#xD;
  &#xD;
            -  Participants' most recent Zubrod performance status must be 0-1 and be documented&#xD;
               within 28 days prior to sub-study randomization&#xD;
  &#xD;
            -  Participants must have a completed medical history and physical exam within 28 days&#xD;
               prior to sub-study randomization&#xD;
  &#xD;
            -  Participants must have adequate cardiac function. Participants with known history or&#xD;
               current symptoms of cardiac disease, or history of treatment with cardiotoxic agents,&#xD;
               must have a clinical risk assessment of cardiac function using the New York Heart&#xD;
               Association Functional Classification. To be eligible for this trial, participants&#xD;
               must be class 2B or better&#xD;
  &#xD;
            -  Participants with known human immunodeficiency virus (HIV)-infection must be on&#xD;
               effective anti-retroviral therapy and have undetectable viral load test on the most&#xD;
               recent test results obtained within 6 months prior to sub-study randomization&#xD;
  &#xD;
            -  Participants with evidence of chronic hepatitis B virus (HBV) infection must have&#xD;
               undetectable HBV viral load while on suppressive therapy on the most recent test&#xD;
               results obtained within 6 months prior to sub-study randomization, if indicated&#xD;
  &#xD;
            -  Participants with a history of hepatitis C virus (HCV) infection must have been&#xD;
               treated and cured. Participants currently being treated for HCV infection must have&#xD;
               undetectable HCV viral load test on the most recent test results obtained within 6&#xD;
               months prior to sub-study randomization, if indicated by the treating investigator&#xD;
  &#xD;
            -  Participants must not have cirrhosis at a level of Child-Pugh B (or worse) OR any&#xD;
               degree of cirrhosis AND a history of hepatic encephalopathy or clinically meaningful&#xD;
               ascites resulting from cirrhosis&#xD;
  &#xD;
            -  Participants must not have grade &lt; 0 of peripheral edema within 28 days prior to&#xD;
               sub-study randomization&#xD;
  &#xD;
            -  Participants must not have experienced any arterial thromboembolic events, including&#xD;
               but not limited to transient ischemic attack or cerebrovascular accident within 6&#xD;
               months prior to sub-study randomization&#xD;
  &#xD;
            -  Participants must not have uncontrolled blood pressure and hypertension within 28 days&#xD;
               prior to sub-study randomization&#xD;
  &#xD;
            -  Participants must not be pregnant or breastfeeding (nursing includes breast milk fed&#xD;
               to an infant by any means, including from the breast, milk expressed by hand, or&#xD;
               pumped). Individuals who are of reproductive potential must have agreed to use an&#xD;
               effective contraceptive method with details provided as a part of the consent process.&#xD;
               A person who has had menses at any time in the preceding 12 consecutive months or who&#xD;
               has semen likely to contain sperm is considered to be of &quot;reproductive potential.&quot; In&#xD;
               addition to routine contraceptive methods, &quot;effective contraception&quot; also includes&#xD;
               refraining from sexual activity that might result in pregnancy and surgery intended to&#xD;
               prevent pregnancy (or with a side-effect of pregnancy prevention) including&#xD;
               hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and&#xD;
               vasectomy with testing showing no sperm in the semen&#xD;
  &#xD;
            -  Participants must have a Lymphoscintigraphy scan performed within 28 days prior to&#xD;
               sub-study randomization&#xD;
  &#xD;
            -  Participants must also be offered participation in specimen banking. With participant&#xD;
               consent, specimens must be collected and submitted via the SWOG Specimen Tracking&#xD;
               System&#xD;
  &#xD;
            -  Participants must be informed of the investigational nature of this study and must&#xD;
               sign and give informed consent in accordance with institutional and federal guidelines&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>N/A</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Paul K Paik</last_name>
      <role>Principal Investigator</role>
      <affiliation>SWOG Cancer Research Network</affiliation>
    </overall_official>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 28, 2023</study_first_submitted>
    <study_first_submitted_qc>September 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 11, 2023</study_first_posted>
    <last_update_submitted>September 7, 2023</last_update_submitted>
    <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lung Neoplasms</mesh_term>
      <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Antineoplastic Agents, Immunological</mesh_term>
      <mesh_term>Ramucirumab</mesh_term>
      <mesh_term>Tepotinib</mesh_term>
      <mesh_term>Antibodies</mesh_term>
      <mesh_term>Immunoglobulins</mesh_term>
      <mesh_term>Antibodies, Monoclonal</mesh_term>
      <mesh_term>Lexatumumab</mesh_term>
    </intervention_browse>
    <!-- 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/NCT06031688
  org study id: S1900K
  secondary id: NCI-2023-04727
  secondary id: S1900K
  secondary id: S1900K
  secondary id: U10CA180888
  nct id: NCT06031688
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This phase II Expanded Lung-MAP treatment trial tests tepotinib with or without ramucirumab
        for the treatment of patients with advanced non-small cell lung cancer that has spread from
        where it first started (primary site) to other places in the body (stage IV) or that has come
        back after a period of improvement (recurrent). Tepotinib is used in patients whose cancer
        has a mutated (changed) form of a gene called MET. It is in a class of medications called
        kinase inhibitors. It works by blocking the action of the abnormal MET protein that signals
        tumor cells to multiply. This helps slow or stop the spread of tumor cells. Ramucirumab is a
        monoclonal antibody that may prevent the growth of new blood vessels that tumors need to
        grow. Giving tepotinib with ramucirumab may lower the chance of the cancer from growing or
        spreading in patients with stage IV or recurrent non-small cell lung cancer.
  PRIMARY OBJECTIVE:
  
        I. To compare the response rate (confirmed or unconfirmed, complete or impartial) between
        participants with MET exon 14 skipping positive non-small cell lung cancer (NSCLC) randomized
        to tepotinib with or without ramucirumab.
  
        SECONDARY OBJECTIVES:
  
        I. To compare the frequency of all-grade treatment- related peripheral edema as defined by
        Common Terminology Criteria for Adverse Events (CTCAE) between the arms.
  
        II. To evaluate the frequency and severity of toxicities within each arm. III. To compare
        progression-free survival between the arms. IV. To compare overall survival between the arms.
        V. To estimate the duration of response (DoR) among responders within each arm.
  
        TRANSLATIONAL MEDICINE OBJECTIVE:
  
        I. To establish a tissue/blood repository for participants with MET exon 14 skipping
        non-small cell lung cancer (NSCLC).
  
        OUTLINE: Patients are randomized to 1 of 2 arms.
  
        ARM A: Patients receive ramucirumab intravenously (IV) over 30-60 minutes on day 1 of each
        cycle and tepotinib orally (PO) once daily (QD) on days 1-21 of each cycle. Cycles repeat
        every 21 days in the absence of disease progression or unacceptable toxicity.
  
        ARM B: Patients receive tepotinib PO QD on days 1-21 of each cycle. Cycles repeat every 21
        days in the absence of disease progression or unacceptable toxicity.
  
        Patients undergo lymphoscintigraphy scan and computed tomography (CT) scan and/or magnetic
        resonance imaging (MRI) throughout the trial. Patients also undergo blood sample collection
        while on study.
  
        After completion of study treatment, patients are followed-up every 12 weeks or more often as
        clinically indicated until progression and then every 6 months for 2 years and at the end of
        3 years from date of sub-study randomization.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Response rate
  time frame: Up to 3 years from date of sub-study randomization
  description: Rates will be compared using a chi-squared test at the 1-sided 10% level and also presented as the difference in response rates with the associated 80% confidence interval for the difference, Further, response rates and associated 80% confidence interval will be estimated for each arm.
  measure: Frequency of treatment-related peripheral edema
  time frame: Up to 3 years from date of sub-study randomization
  description: The frequency of peripheral edema will be compared using a 2-sided 10% level test of proportions. All-grade peripheral edema will be estimated along with 90% confidence intervals. Data from lymphoscintigraphy imaging will be summarized for baseline and among those with peripheral edema.
  measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
  time frame: Up to 3 years from date of sub-study randomization
  description: The number of participants with treatment-related adverse events as assessed by CTCAE v5.0 within each treatment arm will be evaluated.
  measure: Progression-free survival
  time frame: From date of sub-study randomization to date of first documentation of progression or death due to any cause, assessed up to 3 years
  description: Will be estimated using the method of Kaplan-Meier. Will be compared between the arms using a 1-sided 10% level log-rank test. Medians and associated 80% confidence intervals will be estimated using the Brookmeyer-Crowley method.
  measure: Overall survival
  time frame: Up to 3 years from date of sub-study randomization
  description: Will be estimated using the method of Kaplan-Meier. Medians and associated 80% confidence intervals will be estimated using the Brookmeyer-Crowley method.
  measure: Duration of response
  time frame: From date of first documentation of response (complete response [CR] or partial response [PR]) to date of first documentation of progression or death due to any cause among participants who achieve a response (CR or PR), assessed up to 3 years
  description: Will be estimated using the method of Kaplan-Meier. Medians and associated 80% confidence intervals will be estimated using the Brookmeyer-Crowley method.
  arm group label: Arm A: (Ramucirumab and tepotinib)
  arm group type: Experimental
  description: Patients receive ramucirumab IV over 30-60 minutes on day 1 of each cycle and tepotinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo lymphoscintigraphy scan and CT scan and/or MRI throughout the trial. Patients also undergo blood sample collection while on study.
  arm group label: Arm B: (Tepotinib)
  arm group type: Active Comparator
  description: Patients receive tepotinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo lymphoscintigraphy scan and CT scan and/or MRI throughout the trial. Patients also undergo blood sample collection while on study.
  intervention type: Procedure
  intervention name: Biospecimen Collection
  description: Undergo blood sample collection
  arm group label: Arm A: (Ramucirumab and tepotinib)
  arm group label: Arm B: (Tepotinib)
  other name: Biological Sample Collection
  other name: Biospecimen Collected
  other name: Specimen Collection
  intervention type: Procedure
  intervention name: Computed Tomography
  description: Undergo CT scan
  arm group label: Arm A: (Ramucirumab and tepotinib)
  arm group label: Arm B: (Tepotinib)
  other name: CAT
  other name: CAT Scan
  other name: Computed Axial Tomography
  other name: Computerized Axial Tomography
  other name: Computerized axial tomography (procedure)
  other name: Computerized Tomography
  other name: CT
  other name: CT Scan
  other name: tomography
  intervention type: Procedure
  intervention name: Lymphoscintigraphy
  description: Undergo lymphoscintigraphy scan
  arm group label: Arm A: (Ramucirumab and tepotinib)
  arm group label: Arm B: (Tepotinib)
  intervention type: Procedure
  intervention name: Magnetic Resonance Imaging
  description: Undergo MRI
  arm group label: Arm A: (Ramucirumab and tepotinib)
  arm group label: Arm B: (Tepotinib)
  other name: Magnetic Resonance
  other name: Magnetic resonance imaging (procedure)
  other name: Magnetic Resonance Imaging Scan
  other name: Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  other name: MR
  other name: MR Imaging
  other name: MRI
  other name: MRI Scan
  other name: NMR Imaging
  other name: NMRI
  other name: Nuclear Magnetic Resonance Imaging
  intervention type: Biological
  intervention name: Ramucirumab
  description: Given IV
  arm group label: Arm A: (Ramucirumab and tepotinib)
  other name: Anti-VEGFR-2 Fully Human Monoclonal Antibody IMC-1121B
  other name: Cyramza
  other name: IMC-1121B
  other name: LY3009806
  other name: Monoclonal Antibody HGS-ETR2
  intervention type: Drug
  intervention name: Tepotinib
  description: Given PO
  arm group label: Arm A: (Ramucirumab and tepotinib)
  arm group label: Arm B: (Tepotinib)
  other name: c-Met Inhibitor MSC2156119J
  other name: EMD 1214063
  other name: EMD-1214063
  other name: EMD1214063
  other name: MSC2156119J
  criteria: 
  gender: All
  minimum age: N/A
  maximum age: N/A
  healthy volunteers: No
  last name: Paul K Paik
  role: Principal Investigator
  affiliation: SWOG Cancer Research Network
  responsible party type: Sponsor
  mesh term: Lung Neoplasms
  mesh term: Carcinoma, Non-Small-Cell Lung
  mesh term: Antineoplastic Agents, Immunological
  mesh term: Ramucirumab
  mesh term: Tepotinib
  mesh term: Antibodies
  mesh term: Immunoglobulins
  mesh term: Antibodies, Monoclonal
  mesh term: Lexatumumab