<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/NCT03748927</url>
  </required_header>
  <id_info>
    <org_study_id>190021</org_study_id>
    <secondary_id>19-C-0021</secondary_id>
    <nct_id>NCT03748927</nct_id>
  </id_info>
  <brief_title>Natural History Study of Children and Adults With Fibrolamellar Hepatocellular Carcinoma</brief_title>
  <official_title>A Natural History Study of Children and Adults With Fibrolamellar Hepatocellular Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      Fibrolamellar Hepatocellular Carcinoma (FL-HCC) is a rare liver cancer. It usually occurs in&#xD;
      young people who have no history of liver disease. Currently the only effective treatment&#xD;
      option is surgery that removes the tumor and part of the liver. Researchers want to study the&#xD;
      course of the disease to learn more about it.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To collect samples from people with FL-HCC to learn more about the disease and help develop&#xD;
      new treatments.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      People any age with FL-HCC&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants must be enrolled on another NIH protocol.&#xD;
&#xD;
      Participants will have at least 1 study visit. They will have:&#xD;
&#xD;
        -  A medical and cancer history&#xD;
&#xD;
        -  A physical exam&#xD;
&#xD;
        -  A review of their symptoms and their ability to do normal activities&#xD;
&#xD;
        -  Tests to produce images of the body. They may have a scan (CT) that uses a small amount&#xD;
           of radiation. Or they may have a scan (MRI) that uses a magnetic field. These will&#xD;
           examine the chest, abdomen, and pelvis.&#xD;
&#xD;
        -  Blood tests&#xD;
&#xD;
      Researchers will study previous tumor samples if they are available.&#xD;
&#xD;
      If participants come to NIH for visits on other studies, data will be collected about their&#xD;
      disease, tests, treatments, and responses. Tumor tissue will be collected if participants are&#xD;
      having it taken for a procedure.&#xD;
&#xD;
      All other participants will be contacted to collect this data. They will be contacted once a&#xD;
      month for 1 year and 2 times a year after that.&#xD;
&#xD;
      Participants will be asked to contact researchers when their health changes. They may come in&#xD;
      for more tests.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
        -  Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare hepatocellular carcinoma&#xD;
           accounting for 0.5-9% of primary liver cancer in various case series, which is usually&#xD;
           not associated with elevated serum alpha fetoprotein (AFP) levels, is enriched in&#xD;
           younger age groups, and is not associated with underlying liver disease.&#xD;
&#xD;
        -  Reports on the characteristics of patients with FL-HCC as well as predictors of&#xD;
           recurrence and survival are scarce, largely due to the rarity of this tumor. The only&#xD;
           potentially curative treatment option for FL-HCC patients who have resectable disease is&#xD;
           surgery: either liver resection (LR) or liver transplantation (LT). However, disease&#xD;
           recurrence after complete surgical resection is high, ranging from 33-100%. The clinical&#xD;
           outcome of patients with unresectable disease is suboptimal with median survival of less&#xD;
           than 12 months and no patient surviving beyond 5 years.&#xD;
&#xD;
        -  The role of neoadjuvant and adjuvant therapies, including systemic chemotherapy, remains&#xD;
           poorly defined and has been reported to have only a modest or no therapeutic effect.&#xD;
           Platinum-based chemotherapy in pediatric patients with FL-HCC resulted a partial&#xD;
           response in 31% of patients on imaging but a 3-year survival of only 22%. To date no&#xD;
           targeted therapy has been shown to be of any value in this disease.&#xD;
&#xD;
        -  The natural history of FL-HCC varies greatly with most patients surviving only months&#xD;
           while others can live with the disease for years. While one cannot exclude an immune or&#xD;
           other host component as responsible for the diverse clinical courses, it is also&#xD;
           possible that there may be a genetic basis for this phenomenon. A novel somatic&#xD;
           recurrent 400 kb deletion on the short arm of chromosome 19, giving rise to an in-frame&#xD;
           DNAJB1 PRKACA gene fusion was found in FL-HCC. mTOR signaling is significantly activated&#xD;
           in FL-HCC compared to other liver malignancies. A bio-specimen repository will be a&#xD;
           major step towards more comprehensive studies of this very rare and unusual tumor and&#xD;
           allow us to begin to characterize subgroups within the disease.&#xD;
&#xD;
        -  Patients with rare tumors seek expert advice in the management of their care. A natural&#xD;
           history study would establish a more formal mechanism for such referrals, while allowing&#xD;
           the systematic collection of epidemiologic data as well as much needed tumor samples.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      - Characterize the natural history of Fibrolamellar hepatocellular carcinoma (FL-HCC),&#xD;
      including clinical presentation, family history, patterns of disease progression, response or&#xD;
      lack of response to therapeutic interventions, disease recurrence and overall survival.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      - Subjects of all ages with histologically or cytologically proven FL-HCC.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Participants will undergo a comprehensive study entry evaluation including clinical&#xD;
           phenotyping and imaging of tumor sites. Computed tomography scans of the thorax, abdomen&#xD;
           and pelvis may be performed if clinically indicated; occasionally, magnetic resonance&#xD;
           imaging may be performed for the visualization of lesions in the liver, spine, or other&#xD;
           anatomic sites if clinically indicated.&#xD;
&#xD;
        -  Medical histories will be documented, and participants will be followed throughout the&#xD;
           course of their illnesses, with attention to patterns of disease recurrence and&#xD;
           progression, response to therapies and duration of responses. As part of this natural&#xD;
           history study, growth rates of target tumor lesions will also be calculated throughout&#xD;
           the course of the disease whenever available.&#xD;
&#xD;
        -  Blood and tumor samples will be obtained at study entry and while on study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    slow/insufficient accrual&#xD;
  </why_stopped>
  <start_date type="Actual">April 8, 2019</start_date>
  <completion_date type="Actual">March 23, 2020</completion_date>
  <primary_completion_date type="Actual">March 23, 2020</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>Characterize the natural history of Fibrolamellar hepatocellular carcinoma (FL- HCC), including clinical presentation, family history, patterns of disease progression, response or lack of response to therapeutic interventions, disease recurre...</measure>
    <time_frame>10 years</time_frame>
    <description>Characterize the natural history of Fibrolamellar hepatocellular carcinoma (FL- HCC), including clinical presentation, family history, patterns of disease progression, response or lack of response to therapeutic interventions, disease recurrence and overall survival</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">0</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <condition>Hepatocellular Cancer</condition>
  <arm_group>
    <arm_group_label>1/ Cohort 1</arm_group_label>
    <description>Subjects with FL-HCC.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        primary clinical&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
          -  Subjects enrolled on NCI protocol Natural History and Biospecimen Acquisition Study&#xD;
             for Children and Adults with Rare Solid Tumors&#xD;
&#xD;
          -  Subjects of all ages with histologically or cytologically proven FL-HCC.&#xD;
&#xD;
          -  Ability of subject to understand and the willingness to sign a written informed&#xD;
             consent document.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
        None&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tim F Greten, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Cancer Institute (NCI)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2019-C-0021.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>November 20, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 21, 2018</study_first_posted>
  <last_update_submitted>March 24, 2020</last_update_submitted>
  <last_update_submitted_qc>March 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 26, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Clinical Outcome</keyword>
  <keyword>Advice in the Management of Cancer</keyword>
  <keyword>Patterns of Disease Progression</keyword>
  <keyword>Response or Lack of Response to Therapeutic Interventions</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Hepatocellular</mesh_term>
    <mesh_term>Liver 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/NCT03748927
org study id: 190021
secondary id: 19-C-0021
nct id: NCT03748927
lead sponsor: 
Background:

      Fibrolamellar Hepatocellular Carcinoma (FL-HCC) is a rare liver cancer. It usually occurs in
      young people who have no history of liver disease. Currently the only effective treatment
      option is surgery that removes the tumor and part of the liver. Researchers want to study the
      course of the disease to learn more about it.

      Objective:

      To collect samples from people with FL-HCC to learn more about the disease and help develop
      new treatments.

      Eligibility:

      People any age with FL-HCC

      Design:

      Participants must be enrolled on another NIH protocol.

      Participants will have at least 1 study visit. They will have:

        -  A medical and cancer history

        -  A physical exam

        -  A review of their symptoms and their ability to do normal activities

        -  Tests to produce images of the body. They may have a scan (CT) that uses a small amount
           of radiation. Or they may have a scan (MRI) that uses a magnetic field. These will
           examine the chest, abdomen, and pelvis.

        -  Blood tests

      Researchers will study previous tumor samples if they are available.

      If participants come to NIH for visits on other studies, data will be collected about their
      disease, tests, treatments, and responses. Tumor tissue will be collected if participants are
      having it taken for a procedure.

      All other participants will be contacted to collect this data. They will be contacted once a
      month for 1 year and 2 times a year after that.

      Participants will be asked to contact researchers when their health changes. They may come in
      for more tests.
Background:

        -  Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare hepatocellular carcinoma
           accounting for 0.5-9% of primary liver cancer in various case series, which is usually
           not associated with elevated serum alpha fetoprotein (AFP) levels, is enriched in
           younger age groups, and is not associated with underlying liver disease.

        -  Reports on the characteristics of patients with FL-HCC as well as predictors of
           recurrence and survival are scarce, largely due to the rarity of this tumor. The only
           potentially curative treatment option for FL-HCC patients who have resectable disease is
           surgery: either liver resection (LR) or liver transplantation (LT). However, disease
           recurrence after complete surgical resection is high, ranging from 33-100%. The clinical
           outcome of patients with unresectable disease is suboptimal with median survival of less
           than 12 months and no patient surviving beyond 5 years.

        -  The role of neoadjuvant and adjuvant therapies, including systemic chemotherapy, remains
           poorly defined and has been reported to have only a modest or no therapeutic effect.
           Platinum-based chemotherapy in pediatric patients with FL-HCC resulted a partial
           response in 31% of patients on imaging but a 3-year survival of only 22%. To date no
           targeted therapy has been shown to be of any value in this disease.

        -  The natural history of FL-HCC varies greatly with most patients surviving only months
           while others can live with the disease for years. While one cannot exclude an immune or
           other host component as responsible for the diverse clinical courses, it is also
           possible that there may be a genetic basis for this phenomenon. A novel somatic
           recurrent 400 kb deletion on the short arm of chromosome 19, giving rise to an in-frame
           DNAJB1 PRKACA gene fusion was found in FL-HCC. mTOR signaling is significantly activated
           in FL-HCC compared to other liver malignancies. A bio-specimen repository will be a
           major step towards more comprehensive studies of this very rare and unusual tumor and
           allow us to begin to characterize subgroups within the disease.

        -  Patients with rare tumors seek expert advice in the management of their care. A natural
           history study would establish a more formal mechanism for such referrals, while allowing
           the systematic collection of epidemiologic data as well as much needed tumor samples.

      Objective:

      - Characterize the natural history of Fibrolamellar hepatocellular carcinoma (FL-HCC),
      including clinical presentation, family history, patterns of disease progression, response or
      lack of response to therapeutic interventions, disease recurrence and overall survival.

      Eligibility:

      - Subjects of all ages with histologically or cytologically proven FL-HCC.

      Design:

        -  Participants will undergo a comprehensive study entry evaluation including clinical
           phenotyping and imaging of tumor sites. Computed tomography scans of the thorax, abdomen
           and pelvis may be performed if clinically indicated; occasionally, magnetic resonance
           imaging may be performed for the visualization of lesions in the liver, spine, or other
           anatomic sites if clinically indicated.

        -  Medical histories will be documented, and participants will be followed throughout the
           course of their illnesses, with attention to patterns of disease recurrence and
           progression, response to therapies and duration of responses. As part of this natural
           history study, growth rates of target tumor lesions will also be calculated throughout
           the course of the disease whenever available.

        -  Blood and tumor samples will be obtained at study entry and while on study.
observational model: Cohort
time perspective: Prospective
measure: Characterize the natural history of Fibrolamellar hepatocellular carcinoma (FL- HCC), including clinical presentation, family history, patterns of disease progression, response or lack of response to therapeutic interventions, disease recurre...
time frame: 10 years
description: Characterize the natural history of Fibrolamellar hepatocellular carcinoma (FL- HCC), including clinical presentation, family history, patterns of disease progression, response or lack of response to therapeutic interventions, disease recurrence and overall survival
arm group label: 1/ Cohort 1
description: Subjects with FL-HCC.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 1 Year
maximum age: 99 Years
healthy volunteers: No
last name: Tim F Greten, M.D.
role: Principal Investigator
affiliation: National Cancer Institute (NCI)
facility: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2019-C-0021.html
description: NIH Clinical Center Detailed Web Page
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Liver Neoplasms