<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/NCT04447651</url>
  </required_header>
  <id_info>
    <org_study_id>J1940</org_study_id>
    <nct_id>NCT04447651</nct_id>
  </id_info>
  <brief_title>Patient Response to Immunotherapy Using Spliceosome Mutational Markers (PRISMM)</brief_title>
  <acronym>PRISMM</acronym>
  <official_title>A Remote-Directed &quot;Virtual&quot; Clinical Trial in Metastatic Solid Tumors to Determine Feasibility of Evaluating Patient Response to Immunotherapy Using Spliceosome Mutational Markers (PRISMM)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Vanderbilt University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is being done to see if patients with metastatic solid tumors (hematologic&#xD;
      malignancies and lymphoma excluded) who have a specific genetic mutation in patients' tumor&#xD;
      (the SF3B1, U2AF1 or SRSF2 mutation), are more likely to respond to immunotherapy agents that&#xD;
      are now commercially available.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a non-therapeutic study, meaning that while Johns Hopkins is providing a treatment&#xD;
      recommendation based on participants' genetic information, participants and participants'&#xD;
      oncologist will decide ultimately what to do, and participants' oncologist will monitor&#xD;
      participants' day to day care while on therapy. Participation involves allowing the&#xD;
      investigators access to participants' sequencing report and medical records, providing a&#xD;
      blood sample (about 8 tablespoons) at baseline and possibly again after three months, and&#xD;
      answering questionnaires. If participants join the study, a panel of experts (Johns Hopkins&#xD;
      Molecular Tumor Board) will review participants' genetic information participants entered and&#xD;
      make a determination regarding treatment recommendation. Blood will be collected at baseline&#xD;
      irrespective of what treatment is recommended. If immunotherapy is recommended, the&#xD;
      investigators may collect blood again at 3 months. Participants and participants' oncologist&#xD;
      will ultimately decide if participants proceed with the recommend treatment or not; the&#xD;
      recommendation made from Johns Hopkins is not binding in any way. Participants' oncologist&#xD;
      will continue with usual care according to standard practices while participants are on&#xD;
      therapy. The investigators will get health information and conduct questionnaires with&#xD;
      participants and participants' oncologist to assess how participants are doing on therapy.&#xD;
      The main risks are the discomforts of the blood draw (which are expected to be minor and not&#xD;
      last), boredom from completing questionnaires and the risk that information may become known&#xD;
      to people outside of the study. Participants may or may not benefit directly from being in&#xD;
      the study and there is no payment for participation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 17, 2020</start_date>
  <completion_date type="Anticipated">August 2025</completion_date>
  <primary_completion_date type="Anticipated">August 2023</primary_completion_date>
  <study_type>Observational [Patient Registry]</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>
  <target_duration>3 Years</target_duration>
  <primary_outcome>
    <measure>Feasibility of study as assessed by completion of study accrual within study time frame</measure>
    <time_frame>2 years</time_frame>
    <description>To evaluate the feasibility of conducting a prospective study using online recruitment tools to involve patients and physicians who are not usually served by clinical trials. Measured by enrolling 60 patients over 2 years.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility of study as assessed by physician responses</measure>
    <time_frame>1 year</time_frame>
    <description>To evaluate the feasibility of conducting a prospective study using online recruitment tools to involve patients and physicians who are not usually served by clinical trials. Measured by obtaining responses from 80 percent of physicians within 1 year of enrollment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Feasibility of case review as assessed by time to issuance of recommendations</measure>
    <time_frame>4 weeks from consent</time_frame>
    <description>To evaluate the feasibility of real-time case review by a centralized specialized cancer tumor board to assist in therapeutic decision making. Measured by time (days) to issuance of recommendations within 4 weeks from consent for at least 80 percent of patients.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Metastatic Solid Tumor</condition>
  <condition>SF3B1 Gene Mutation</condition>
  <condition>Spliceosome Mutation</condition>
  <condition>U2AF1 Gene Mutation</condition>
  <condition>SRSF2 Gene Mutation</condition>
  <arm_group>
    <arm_group_label>Patients with SF3B1, U2AF1 or SRSF2 mutation</arm_group_label>
    <description>Metastatic solid tumor patients that have a SF3B1, U2AF1 or SRSF2 mutation</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Recommendation for treatment with immunotherapy</intervention_name>
    <description>Patients with a SF3B1, U2AF1 or SRSF2 mutation will be reviewed by the molecular tumor board and treatment recommendations will be given to the patient's treating oncologist.</description>
    <arm_group_label>Patients with SF3B1, U2AF1 or SRSF2 mutation</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood samples will be collected to:&#xD;
&#xD;
        -  Evaluate whether mutations detected in tumor tissue using various Clinical Laboratory&#xD;
           Improvement Amendments (CLIA)-certified next-generation sequencing assays correlate with&#xD;
           those found in plasma tumor DNA (ptDNA).&#xD;
&#xD;
        -  To evaluate changes in ptDNA from baseline to 3 months in patients with spliceosome&#xD;
           mutations receiving immune checkpoint inhibitors (ICI)&#xD;
&#xD;
        -  To evaluate changes in circulating immune cells (PBMCs) from baseline to 3 months in&#xD;
           patients with spliceosome mutations receiving ICI&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Metastatic solid tumor patients with a SF3B1,U2AF1 or SRSF2 mutation.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Performance status eligible for immune checkpoint blockade as determined by local&#xD;
             physician&#xD;
&#xD;
          -  Able to demonstrate histologically proven locally advanced or metastatic solid tumors&#xD;
             (hematologic malignancies and lymphoma excluded)&#xD;
&#xD;
          -  genomic testing demonstrating a spliceosome mutation (SF3B1, U2AF1 or SRSF2)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Local physician determines has known psychiatric or substance abuse disorders that&#xD;
             would interfere with cooperation with the requirements of the trial&#xD;
&#xD;
          -  Local physician determines the patient has a history or current evidence of any&#xD;
             condition, therapy, or laboratory abnormality that might confound the results of the&#xD;
             trial, interfere with the subject's participation for the full duration of the trial,&#xD;
             or is not in the best interest of the subject to participate&#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>Cesar Santa-Maria, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hopkins Breast Trials</last_name>
    <phone>410-614-1361</phone>
    <email>PRISMM@jhmi.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21236</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>HopkinsBreastTrials</last_name>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>June 22, 2020</study_first_submitted>
  <study_first_submitted_qc>June 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 25, 2020</study_first_posted>
  <last_update_submitted>September 8, 2022</last_update_submitted>
  <last_update_submitted_qc>September 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>sequencing</keyword>
  <keyword>metastatic solid tumor</keyword>
  <keyword>spliceosome mutation</keyword>
  <keyword>immune checkpoint inhibition</keyword>
  <keyword>immunotherapy</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunomodulating Agents</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04447651
org study id: J1940
nct id: NCT04447651
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
This study is being done to see if patients with metastatic solid tumors (hematologic
      malignancies and lymphoma excluded) who have a specific genetic mutation in patients' tumor
      (the SF3B1, U2AF1 or SRSF2 mutation), are more likely to respond to immunotherapy agents that
      are now commercially available.
This is a non-therapeutic study, meaning that while Johns Hopkins is providing a treatment
      recommendation based on participants' genetic information, participants and participants'
      oncologist will decide ultimately what to do, and participants' oncologist will monitor
      participants' day to day care while on therapy. Participation involves allowing the
      investigators access to participants' sequencing report and medical records, providing a
      blood sample (about 8 tablespoons) at baseline and possibly again after three months, and
      answering questionnaires. If participants join the study, a panel of experts (Johns Hopkins
      Molecular Tumor Board) will review participants' genetic information participants entered and
      make a determination regarding treatment recommendation. Blood will be collected at baseline
      irrespective of what treatment is recommended. If immunotherapy is recommended, the
      investigators may collect blood again at 3 months. Participants and participants' oncologist
      will ultimately decide if participants proceed with the recommend treatment or not; the
      recommendation made from Johns Hopkins is not binding in any way. Participants' oncologist
      will continue with usual care according to standard practices while participants are on
      therapy. The investigators will get health information and conduct questionnaires with
      participants and participants' oncologist to assess how participants are doing on therapy.
      The main risks are the discomforts of the blood draw (which are expected to be minor and not
      last), boredom from completing questionnaires and the risk that information may become known
      to people outside of the study. Participants may or may not benefit directly from being in
      the study and there is no payment for participation.
observational model: Cohort
time perspective: Prospective
measure: Feasibility of study as assessed by completion of study accrual within study time frame
time frame: 2 years
description: To evaluate the feasibility of conducting a prospective study using online recruitment tools to involve patients and physicians who are not usually served by clinical trials. Measured by enrolling 60 patients over 2 years.
measure: Feasibility of study as assessed by physician responses
time frame: 1 year
description: To evaluate the feasibility of conducting a prospective study using online recruitment tools to involve patients and physicians who are not usually served by clinical trials. Measured by obtaining responses from 80 percent of physicians within 1 year of enrollment.
measure: Feasibility of case review as assessed by time to issuance of recommendations
time frame: 4 weeks from consent
description: To evaluate the feasibility of real-time case review by a centralized specialized cancer tumor board to assist in therapeutic decision making. Measured by time (days) to issuance of recommendations within 4 weeks from consent for at least 80 percent of patients.
arm group label: Patients with SF3B1, U2AF1 or SRSF2 mutation
description: Metastatic solid tumor patients that have a SF3B1, U2AF1 or SRSF2 mutation
intervention type: Other
intervention name: Recommendation for treatment with immunotherapy
description: Patients with a SF3B1, U2AF1 or SRSF2 mutation will be reviewed by the molecular tumor board and treatment recommendations will be given to the patient's treating oncologist.
arm group label: Patients with SF3B1, U2AF1 or SRSF2 mutation
Blood samples will be collected to:

        -  Evaluate whether mutations detected in tumor tissue using various Clinical Laboratory
           Improvement Amendments (CLIA)-certified next-generation sequencing assays correlate with
           those found in plasma tumor DNA (ptDNA).

        -  To evaluate changes in ptDNA from baseline to 3 months in patients with spliceosome
           mutations receiving immune checkpoint inhibitors (ICI)

        -  To evaluate changes in circulating immune cells (PBMCs) from baseline to 3 months in
           patients with spliceosome mutations receiving ICI
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Cesar Santa-Maria, MD
role: Principal Investigator
affiliation: Johns Hopkins University
last name: Hopkins Breast Trials
phone: 410-614-1361
email: PRISMM@jhmi.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor
mesh term: Immunomodulating Agents