<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/NCT03833934</url>
  </required_header>
  <id_info>
    <org_study_id>ALCMI-011</org_study_id>
    <nct_id>NCT03833934</nct_id>
  </id_info>
  <brief_title>Study of Plasma NGS for Assessment, Characterization, Evaluation of Patients With ALK Resistance</brief_title>
  <acronym>SPACEWALK</acronym>
  <official_title>ALCMI-011: Study of Plasma Next Generation Sequencing for Assessment, Characterization, Evaluation of Patients With ALK Resistance (SPACEWALK)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Addario Lung Cancer Medical Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Dana-Farber Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Addario Lung Cancer Medical Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      ALK-positive lung cancer is a subtype of lung cancer which carries a change in a gene called&#xD;
      ALK (anaplastic lymphoma kinase). There are now many drugs for patients with ALK-positive&#xD;
      lung cancer that slow cancer growth. However, after some time, just as bacteria evolve&#xD;
      resistance to antibiotics, ALK-positive lung cancers evolve ways to avoid the therapies by&#xD;
      developing new mutations so the drugs lost their effectiveness. These new mutations can&#xD;
      potentially be treated with a different drug. For these new therapies, the range of mutations&#xD;
      that can develop at resistance is not well understood.&#xD;
&#xD;
      It is now possible to detect the presence of mutations or changes in the genetic structure in&#xD;
      lung cancer by analyzing a patient's blood for bits of material shed by tumor. This approach&#xD;
      is often called a liquid biopsy. Recently, researchers have shown that looking at tumor&#xD;
      molecules through liquid biopsies can provide doctors with some of the same information that&#xD;
      tissue biopsies provide. For example, liquid biopsies can be used to detect mutations that&#xD;
      cause drug resistance. Obtaining liquid biopsies on patients with ALK-positive lung cancers&#xD;
      at resistance to therapy may help better understand the different mutations that develop and&#xD;
      guide therapy decisions.&#xD;
&#xD;
      In this research study, a blood specimen will be collected and submitted for liquid biopsy&#xD;
      analysis at a commercial diagnostic company. This company specializes in analyzing tumor&#xD;
      material found in blood. Specifically, it will look for genetic changes in the ALK gene that&#xD;
      could help understand why a cancer has developed drug resistance.&#xD;
&#xD;
      This research study is for lung cancer patients with ALK-positive lung cancer who had been on&#xD;
      a newer ALK targeted treatment (such as ceritinib, alectinib, brigatinib, or lorlatinib) to&#xD;
      determine whether they have developed ALK resistance mutations. The investigators will&#xD;
      collect a blood sample to examine these mutations. Participants will not have to have a&#xD;
      tissue biopsy to participate in this study. Participants do not have to visit Dana-Farber&#xD;
      Cancer Institute (DFCI) to participate. All study procedures will be performed remotely.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      SPACEWALK is an innovative remote consent and participation study using next-generation&#xD;
      sequencing (NGS) of plasma cell-free DNA (cfDNA) to characterize resistance mechanisms&#xD;
      arising in ALK-positive non-small cell lung cancer (NSCLC) after progression while on a next&#xD;
      generation ALK tyrosine kinase inhibitor (TKI). Additionally, the study will capture the&#xD;
      potential of genomic-driven resistance therapy approach for effecting outcomes in patients&#xD;
      with advanced ALK-positive NSCLC and TKI resistance. Finally, the study will assess the role&#xD;
      of repeat plasma NGS in evaluating drug response.&#xD;
&#xD;
      The study will accrue patients with advanced ALK-positive NSCLC on systemic progression&#xD;
      (outside the brain) while on treatment with a next-generation ALK TKI. Any patient interested&#xD;
      in the study will find information about the study on the study website. The patient will&#xD;
      consent remotely through the study website and documentation of advanced ALK-positive NSCLC&#xD;
      and systemic progression while on a next-generation ALK TKI. The study team will then reach&#xD;
      out to the patient to confirm eligibility and send a blood collection kit. In the study kit&#xD;
      the study participants will find all the necessary materials for local blood draws and&#xD;
      collected specimens will be sent directly to the central study laboratory (Resolution&#xD;
      Bioscience) for plasma NGS.&#xD;
&#xD;
      Plasma NGS of cfDNA will involve sequencing of 19 genes, including ALK, permitting remote&#xD;
      tumor genotyping. Plasma NGS analysis and results will be done following standard procedures&#xD;
      of the Resolution Bioscience CLIA-certified laboratory. Results will take 1-2 weeks to be&#xD;
      sent back to study participants, their physicians and study team. Those plasma NGS reports&#xD;
      will not include any specific treatment recommendations but will describe the presence of an&#xD;
      ALK rearrangement, ALK resistance mutation, or other relevant mutations.&#xD;
&#xD;
      Study participants are then followed remotely. The study coordinator will contact the&#xD;
      participants weekly for 4 weeks after enrolled into the study to learn of any new treatment&#xD;
      initiation and to release an additional plasma collection kit 2-4 weeks after starting&#xD;
      treatment. Study participants will then be remotely contacted every 3 months to follow&#xD;
      clinical outcomes on therapy for up to 2 years. If the cancer begins to grow again on the&#xD;
      participant's new treatment, the patient will have the option to provide a third blood&#xD;
      specimen. Medical records and local imaging will be collected and studied.&#xD;
&#xD;
      The primary objective of the study is to characterize ALK TKI resistance to next-generation&#xD;
      ALK TKIs in patients with advanced ALK-positive NSCLC. Secondarily, the investigators will&#xD;
      assess the potential of plasma NGS to impact outcome on treatment by studying time to&#xD;
      treatment discontinuation (TTD). Serial plasma NGS will also be assessed as a response&#xD;
      biomarker. A total of 300 patients will be enrolled, with the expectation that approximately&#xD;
      200 will have tumor-related mutations detected in plasma NGS.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 23, 2019</start_date>
  <completion_date type="Anticipated">March 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">October 30, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Prevalence of ALK resistance mutations after different ALK targeted therapies</measure>
    <time_frame>32 months</time_frame>
    <description>To study the relationship between specific ALK resistance mutations measured through plasma NGS and a specific next gneration ALK TKI received before progression and/or the number of ALK TKIs received</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Sensitivity of plasma NGS for ALK TKI resistance</measure>
    <time_frame>32 months</time_frame>
    <description>To study the feasibility, sensitivity, and turnaround time of plasma NGS in lung cancer patients with ALK TKI resistance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time until treatment discontinuation on subsequent therapy</measure>
    <time_frame>32 months</time_frame>
    <description>To study the survival data of patients with ALK TKI resistance mechanism detected and subsequent therapy received.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">120</enrollment>
  <condition>Non-Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Plasma Next Generation Sequencing (NGS)</arm_group_label>
    <description>Subjects will be sent blood collection kits with the necessary materials for local draws and those specimens will be sent directly by the subjects to the central laboratory (Resolution Bioscience) for plasma NGS. Plasma NGS results will be returned to the subject, their treating physician and study team, aiming to return results within 2 weeks by Resolution Bioscience.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Plasma Next Generation Sequencing (NGS)</intervention_name>
    <description>Liquid biospys</description>
    <arm_group_label>Plasma Next Generation Sequencing (NGS)</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood specimens will be tested for genetic mutations in ALK and other genes that may be&#xD;
      important for lung cancer. The participant and their doctor will receive a copy of the test&#xD;
      results. The test results will describe the gene alterations that are detected in the blood&#xD;
      sample. The assay covers a region of the ALK gene and other lung cancer genes where&#xD;
      resistance alterations can occur.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        This research study is for lung cancer patients with ALK-positive lung cancer who had been&#xD;
        on a newer ALK targeted treatment (such as ceritinib, alectinib, brigatinib, or&#xD;
        larlatinib).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men or women older than 18 years at the time of consent.&#xD;
&#xD;
          -  Demonstration of having advanced ALK positive NSCLC.&#xD;
&#xD;
          -  Systemic progression (not CNS only progression) within the past 30 days while&#xD;
             receiving a next generation ALK TKI.&#xD;
&#xD;
          -  Patient must not have started a new line of therapy before signing the informed&#xD;
             consent form.&#xD;
&#xD;
          -  Willingness to provide a blood specimen prior to the initiation of a new line of&#xD;
             treatment.&#xD;
&#xD;
          -  Willing to provide clinical and medical information to the study team as required.&#xD;
&#xD;
          -  Ability to read, write and communicate in English.&#xD;
&#xD;
          -  Ability to sign a web-based informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants who are unable to provide informed consent.&#xD;
&#xD;
          -  Participants who are 18 years of age or younger.&#xD;
&#xD;
          -  Participants who are unable to comply with the study procedures.&#xD;
&#xD;
          -  Known existence of an uncontrolled intercurrent illness including, but not limited to,&#xD;
             psychiatric illness or social situations that would impair compliance with study&#xD;
             requirements.&#xD;
&#xD;
          -  Participants who have previously enrolled to the study&#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>Geoffrey R Oxnard, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dana-Farber Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>January 28, 2019</study_first_submitted>
  <study_first_submitted_qc>February 6, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 7, 2019</study_first_posted>
  <last_update_submitted>January 26, 2023</last_update_submitted>
  <last_update_submitted_qc>January 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ALK positive</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03833934
org study id: ALCMI-011
nct id: NCT03833934
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
ALK-positive lung cancer is a subtype of lung cancer which carries a change in a gene called
      ALK (anaplastic lymphoma kinase). There are now many drugs for patients with ALK-positive
      lung cancer that slow cancer growth. However, after some time, just as bacteria evolve
      resistance to antibiotics, ALK-positive lung cancers evolve ways to avoid the therapies by
      developing new mutations so the drugs lost their effectiveness. These new mutations can
      potentially be treated with a different drug. For these new therapies, the range of mutations
      that can develop at resistance is not well understood.

      It is now possible to detect the presence of mutations or changes in the genetic structure in
      lung cancer by analyzing a patient's blood for bits of material shed by tumor. This approach
      is often called a liquid biopsy. Recently, researchers have shown that looking at tumor
      molecules through liquid biopsies can provide doctors with some of the same information that
      tissue biopsies provide. For example, liquid biopsies can be used to detect mutations that
      cause drug resistance. Obtaining liquid biopsies on patients with ALK-positive lung cancers
      at resistance to therapy may help better understand the different mutations that develop and
      guide therapy decisions.

      In this research study, a blood specimen will be collected and submitted for liquid biopsy
      analysis at a commercial diagnostic company. This company specializes in analyzing tumor
      material found in blood. Specifically, it will look for genetic changes in the ALK gene that
      could help understand why a cancer has developed drug resistance.

      This research study is for lung cancer patients with ALK-positive lung cancer who had been on
      a newer ALK targeted treatment (such as ceritinib, alectinib, brigatinib, or lorlatinib) to
      determine whether they have developed ALK resistance mutations. The investigators will
      collect a blood sample to examine these mutations. Participants will not have to have a
      tissue biopsy to participate in this study. Participants do not have to visit Dana-Farber
      Cancer Institute (DFCI) to participate. All study procedures will be performed remotely.
SPACEWALK is an innovative remote consent and participation study using next-generation
      sequencing (NGS) of plasma cell-free DNA (cfDNA) to characterize resistance mechanisms
      arising in ALK-positive non-small cell lung cancer (NSCLC) after progression while on a next
      generation ALK tyrosine kinase inhibitor (TKI). Additionally, the study will capture the
      potential of genomic-driven resistance therapy approach for effecting outcomes in patients
      with advanced ALK-positive NSCLC and TKI resistance. Finally, the study will assess the role
      of repeat plasma NGS in evaluating drug response.

      The study will accrue patients with advanced ALK-positive NSCLC on systemic progression
      (outside the brain) while on treatment with a next-generation ALK TKI. Any patient interested
      in the study will find information about the study on the study website. The patient will
      consent remotely through the study website and documentation of advanced ALK-positive NSCLC
      and systemic progression while on a next-generation ALK TKI. The study team will then reach
      out to the patient to confirm eligibility and send a blood collection kit. In the study kit
      the study participants will find all the necessary materials for local blood draws and
      collected specimens will be sent directly to the central study laboratory (Resolution
      Bioscience) for plasma NGS.

      Plasma NGS of cfDNA will involve sequencing of 19 genes, including ALK, permitting remote
      tumor genotyping. Plasma NGS analysis and results will be done following standard procedures
      of the Resolution Bioscience CLIA-certified laboratory. Results will take 1-2 weeks to be
      sent back to study participants, their physicians and study team. Those plasma NGS reports
      will not include any specific treatment recommendations but will describe the presence of an
      ALK rearrangement, ALK resistance mutation, or other relevant mutations.

      Study participants are then followed remotely. The study coordinator will contact the
      participants weekly for 4 weeks after enrolled into the study to learn of any new treatment
      initiation and to release an additional plasma collection kit 2-4 weeks after starting
      treatment. Study participants will then be remotely contacted every 3 months to follow
      clinical outcomes on therapy for up to 2 years. If the cancer begins to grow again on the
      participant's new treatment, the patient will have the option to provide a third blood
      specimen. Medical records and local imaging will be collected and studied.

      The primary objective of the study is to characterize ALK TKI resistance to next-generation
      ALK TKIs in patients with advanced ALK-positive NSCLC. Secondarily, the investigators will
      assess the potential of plasma NGS to impact outcome on treatment by studying time to
      treatment discontinuation (TTD). Serial plasma NGS will also be assessed as a response
      biomarker. A total of 300 patients will be enrolled, with the expectation that approximately
      200 will have tumor-related mutations detected in plasma NGS.
observational model: Cohort
time perspective: Prospective
measure: Prevalence of ALK resistance mutations after different ALK targeted therapies
time frame: 32 months
description: To study the relationship between specific ALK resistance mutations measured through plasma NGS and a specific next gneration ALK TKI received before progression and/or the number of ALK TKIs received
measure: Sensitivity of plasma NGS for ALK TKI resistance
time frame: 32 months
description: To study the feasibility, sensitivity, and turnaround time of plasma NGS in lung cancer patients with ALK TKI resistance.
measure: Time until treatment discontinuation on subsequent therapy
time frame: 32 months
description: To study the survival data of patients with ALK TKI resistance mechanism detected and subsequent therapy received.
arm group label: Plasma Next Generation Sequencing (NGS)
description: Subjects will be sent blood collection kits with the necessary materials for local draws and those specimens will be sent directly by the subjects to the central laboratory (Resolution Bioscience) for plasma NGS. Plasma NGS results will be returned to the subject, their treating physician and study team, aiming to return results within 2 weeks by Resolution Bioscience.
intervention type: Diagnostic Test
intervention name: Plasma Next Generation Sequencing (NGS)
description: Liquid biospys
arm group label: Plasma Next Generation Sequencing (NGS)
Blood specimens will be tested for genetic mutations in ALK and other genes that may be
      important for lung cancer. The participant and their doctor will receive a copy of the test
      results. The test results will describe the gene alterations that are detected in the blood
      sample. The assay covers a region of the ALK gene and other lung cancer genes where
      resistance alterations can occur.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Geoffrey R Oxnard, MD
role: Principal Investigator
affiliation: Dana-Farber Cancer Institute
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
sharing ipd: No