<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/NCT03276702</url>
  </required_header>
  <id_info>
    <org_study_id>REBIOP</org_study_id>
    <nct_id>NCT03276702</nct_id>
  </id_info>
  <brief_title>Tumor Rebiopsy in Children and Adolescents With Recurrent or Progressive Solid Malignancies</brief_title>
  <official_title>A Protocol for Prospectively Collecting Fresh Tumor Tissue in Children and Adolescents With Recurrent or Progressive Solid Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Jude Children's Research Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>St. Jude Children's Research Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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>
      It has been shown that the genomic landscape of tumors can dramatically change at the time of&#xD;
      disease progression. This suggests that therapies aimed at treating the tumor at diagnosis&#xD;
      may not be relevant at the time of relapse. Obtaining fresh tissue at the time of relapse&#xD;
      could facilitate the identification of potential targets that have developed through&#xD;
      mutational evolution of the primary tumor and would provide an unprecedented opportunity to&#xD;
      expand the library of patient derived xenografts (PDX) that are available for comprehensive&#xD;
      preclinical testing in the setting of relapsed disease.&#xD;
&#xD;
      The purpose of this observational study is to prospectively collect fresh tumor tissue from&#xD;
      pediatric patients with solid tumors who have recurrent or progressive disease and submit&#xD;
      this tissue for comprehensive genomic analysis using clinically available CLIA-certified&#xD;
      platforms that include WGS, WES and RNAseq, and to assess the reasons for a patient and/or a&#xD;
      parent for making a decision to proceed with or refuse a re-biopsy procedure in the presence&#xD;
      of a recurrent or progressive solid tumor. The data obtained will be used to develop new&#xD;
      novel therapies that incorporate new pharmacological agents in pediatric solid tumors.&#xD;
&#xD;
      PRIMARY OBJECTIVES:&#xD;
&#xD;
        -  To prospectively collect fresh tumor tissue from pediatric patients with solid tumors&#xD;
           who have recurrent or progressive disease and submit this tissue for comprehensive&#xD;
           genomic analysis.&#xD;
&#xD;
        -  To assess the reasons a patient and/or a parent make the decision to proceed with or&#xD;
           refuse a re-biopsy procedure in the presence of a recurrent or progressive solid tumor.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
        -  To estimate refusal and acceptance rates for re-biopsy and the parental/patient&#xD;
           attitudes towards a re-biopsy.&#xD;
&#xD;
        -  To estimate the incidence of complications associated with biopsy.&#xD;
&#xD;
        -  To estimate the percentage of procedures that fail to obtain adequate tissue for genomic&#xD;
           analysis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, non-therapeutic study with two components: biopsy of tumor for genomic&#xD;
      studies and prospective assessment of parental factors related to participation. All patients&#xD;
      at St. Jude Children's Research Hospital (SJCRH) who meet the eligibility criteria will be&#xD;
      approached for study participation. The re-biopsy is not mandatory and will only be performed&#xD;
      after the patient and family have consented. A questionnaire to assess the impact and&#xD;
      perception of an optional/research only biopsy will be administered following the decision&#xD;
      regarding re-biopsy. For those consenting to the re-biopsy, approximately 4-8 weeks after&#xD;
      biopsy, the family and patient will be asked to complete a second questionnaire to assess&#xD;
      decisional regret.&#xD;
&#xD;
      Participants may repeat participation in this trial with subsequent relapses, provided&#xD;
      informed consent is obtained prior to each re-biopsy procedure. For those participants who&#xD;
      consent to repeat participation, all protocol procedures will be repeated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 13, 2017</start_date>
  <completion_date type="Actual">July 31, 2019</completion_date>
  <primary_completion_date type="Actual">July 31, 2019</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>Percent of good quality tumor samples obtained</measure>
    <time_frame>Once at study enrollment</time_frame>
    <description>Good quality of the sampled tumor is defined as greater than 50% viable tumor from which at least 2 µg DNA and 1 µg RNA can be extracted.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">8</enrollment>
  <condition>Tumor, Solid</condition>
  <arm_group>
    <arm_group_label>Participants</arm_group_label>
    <description>St. Jude Children's Research Hospital patients with relapsed or progressive solid tumor will be asked to complete a questionnaire on two occasions and optional re-biopsy of tumor tissue.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Re-biopsy</intervention_name>
    <description>For those participants who agree, a biopsy of their tumor to obtain tissue for genetic analysis will be done at the time of relapse or disease progression.</description>
    <arm_group_label>Participants</arm_group_label>
    <other_name>Tumor tissue biopsy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire</intervention_name>
    <description>Parents or patients will be asked to complete a questionnaire to assess the impact and perception of an optional/research only biopsy. A second questionnaire will be administered approximately 4-8 weeks after biopsy to assess decisional regret.</description>
    <arm_group_label>Participants</arm_group_label>
    <other_name>Assessment</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      DNA will be extracted from the patient's peripheral blood and tumor samples and RNA will be&#xD;
      extracted from the tumor sample and whole genome sequencing (WGS), whole exome sequencing&#xD;
      (WES) and transcriptome sequencing (RNA-Seq) will be performed on Illumina Next Generation&#xD;
      Sequencers. Both somatic and germline variants (single nucleotide variants, structural&#xD;
      variants, insertions/deletions, and copy number variants) will be identified using a&#xD;
      bioinformatics pipeline developed and validated at SJCRH. Separate reports will be generated&#xD;
      for the somatic lesions and germline lesions. In the event that there is not enough fresh&#xD;
      tissue to perform WGS, WES and RNAseq will be performed in FFPE material if available.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        St. Jude Children's Research Hospital patient with a solid tumor malignancy that is&#xD;
        progressive or recurrent.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 2-21 years&#xD;
&#xD;
          -  Patient has been diagnosed with a solid tumor malignancy that is recurrent or&#xD;
             progressive and for whom there is no fresh tumor specimen available.&#xD;
&#xD;
          -  Availability of gross disease amenable to biopsy.&#xD;
&#xD;
          -  Karnofsky ≥ 50% for patients &gt;16 years of age and Lansky ≥ 50 for patients ≤ 16 years&#xD;
             of age.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of a non-solid tumor malignancy.&#xD;
&#xD;
          -  Patient with known coagulopathy that requires replacement therapy.&#xD;
&#xD;
          -  Patient with anesthesia risk that would place the patient at a higher than expected&#xD;
             risk for complications (ASA PS4 and ASA PS5).&#xD;
&#xD;
          -  Karnofsky or Lansky performance score of &lt; 50.&#xD;
&#xD;
          -  BMI for age &gt; 95th percentile.&#xD;
&#xD;
          -  Refusal or inability to provide written informed consent according to institutional&#xD;
             guidelines.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alberto Pappo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>St. Jude Children's Research Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St. Jude Children's Research Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.stjude.org</url>
    <description>St. Jude Children's Research Hospital</description>
  </link>
  <link>
    <url>http://www.stjude.org/protocols</url>
    <description>Clinical Trials Open at St. Jude</description>
  </link>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>September 7, 2017</study_first_submitted>
  <study_first_submitted_qc>September 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 8, 2017</study_first_posted>
  <last_update_submitted>June 5, 2023</last_update_submitted>
  <last_update_submitted_qc>June 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 6, 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>Neoplasms</mesh_term>
  </condition_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/NCT03276702
org study id: REBIOP
nct id: NCT03276702
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
It has been shown that the genomic landscape of tumors can dramatically change at the time of
      disease progression. This suggests that therapies aimed at treating the tumor at diagnosis
      may not be relevant at the time of relapse. Obtaining fresh tissue at the time of relapse
      could facilitate the identification of potential targets that have developed through
      mutational evolution of the primary tumor and would provide an unprecedented opportunity to
      expand the library of patient derived xenografts (PDX) that are available for comprehensive
      preclinical testing in the setting of relapsed disease.

      The purpose of this observational study is to prospectively collect fresh tumor tissue from
      pediatric patients with solid tumors who have recurrent or progressive disease and submit
      this tissue for comprehensive genomic analysis using clinically available CLIA-certified
      platforms that include WGS, WES and RNAseq, and to assess the reasons for a patient and/or a
      parent for making a decision to proceed with or refuse a re-biopsy procedure in the presence
      of a recurrent or progressive solid tumor. The data obtained will be used to develop new
      novel therapies that incorporate new pharmacological agents in pediatric solid tumors.

      PRIMARY OBJECTIVES:

        -  To prospectively collect fresh tumor tissue from pediatric patients with solid tumors
           who have recurrent or progressive disease and submit this tissue for comprehensive
           genomic analysis.

        -  To assess the reasons a patient and/or a parent make the decision to proceed with or
           refuse a re-biopsy procedure in the presence of a recurrent or progressive solid tumor.

      SECONDARY OBJECTIVES:

        -  To estimate refusal and acceptance rates for re-biopsy and the parental/patient
           attitudes towards a re-biopsy.

        -  To estimate the incidence of complications associated with biopsy.

        -  To estimate the percentage of procedures that fail to obtain adequate tissue for genomic
           analysis.
This is a prospective, non-therapeutic study with two components: biopsy of tumor for genomic
      studies and prospective assessment of parental factors related to participation. All patients
      at St. Jude Children's Research Hospital (SJCRH) who meet the eligibility criteria will be
      approached for study participation. The re-biopsy is not mandatory and will only be performed
      after the patient and family have consented. A questionnaire to assess the impact and
      perception of an optional/research only biopsy will be administered following the decision
      regarding re-biopsy. For those consenting to the re-biopsy, approximately 4-8 weeks after
      biopsy, the family and patient will be asked to complete a second questionnaire to assess
      decisional regret.

      Participants may repeat participation in this trial with subsequent relapses, provided
      informed consent is obtained prior to each re-biopsy procedure. For those participants who
      consent to repeat participation, all protocol procedures will be repeated.
observational model: Cohort
time perspective: Prospective
measure: Percent of good quality tumor samples obtained
time frame: Once at study enrollment
description: Good quality of the sampled tumor is defined as greater than 50% viable tumor from which at least 2 µg DNA and 1 µg RNA can be extracted.
arm group label: Participants
description: St. Jude Children's Research Hospital patients with relapsed or progressive solid tumor will be asked to complete a questionnaire on two occasions and optional re-biopsy of tumor tissue.
intervention type: Procedure
intervention name: Re-biopsy
description: For those participants who agree, a biopsy of their tumor to obtain tissue for genetic analysis will be done at the time of relapse or disease progression.
arm group label: Participants
other name: Tumor tissue biopsy
intervention type: Other
intervention name: Questionnaire
description: Parents or patients will be asked to complete a questionnaire to assess the impact and perception of an optional/research only biopsy. A second questionnaire will be administered approximately 4-8 weeks after biopsy to assess decisional regret.
arm group label: Participants
other name: Assessment
DNA will be extracted from the patient's peripheral blood and tumor samples and RNA will be
      extracted from the tumor sample and whole genome sequencing (WGS), whole exome sequencing
      (WES) and transcriptome sequencing (RNA-Seq) will be performed on Illumina Next Generation
      Sequencers. Both somatic and germline variants (single nucleotide variants, structural
      variants, insertions/deletions, and copy number variants) will be identified using a
      bioinformatics pipeline developed and validated at SJCRH. Separate reports will be generated
      for the somatic lesions and germline lesions. In the event that there is not enough fresh
      tissue to perform WGS, WES and RNAseq will be performed in FFPE material if available.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 2 Years
maximum age: 21 Years
healthy volunteers: No
last name: Alberto Pappo, MD
role: Principal Investigator
affiliation: St. Jude Children's Research Hospital
facility: 
country: United States
url: http://www.stjude.org
description: St. Jude Children's Research Hospital
url: http://www.stjude.org/protocols
description: Clinical Trials Open at St. Jude
responsible party type: Sponsor
mesh term: Neoplasms