<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/NCT01660984</url>
  </required_header>
  <id_info>
    <org_study_id>120178</org_study_id>
    <secondary_id>12-C-0178</secondary_id>
    <nct_id>NCT01660984</nct_id>
  </id_info>
  <brief_title>Natural History Study of Children and Adults With Medullary Thyroid Cancer</brief_title>
  <official_title>Longitudinal Assessment and Natural History Study of Children and Adults With MEN2A or MEN2B With or Without Medullary Thyroid 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>
  <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>
      Background:&#xD;
&#xD;
      - Medullary thyroid cancer (MTC) is a rare cancer of the thyroid gland. In children and&#xD;
      adults, it is often part of a condition called Multiple Endocrine Neoplasia 2 (MEN2). MEN2 is&#xD;
      usually caused by a genetic mutation, and it can cause a number of problems in addition to&#xD;
      MTC. These problems include adrenal gland tumors, hormone changes, and problems with the&#xD;
      bones and other organs. Not much is known about how MTC develops over time, especially in&#xD;
      people with MEN2. Researchers want to study MTC in children and adults and see how it affects&#xD;
      their growth and development.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      - To study how medullary thyroid cancer affects children and adults over time.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      - Children and adults who have medullary thyroid cancer.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Participants will be screened with a brief physical exam and medical history. Blood and&#xD;
           tissue samples will be collected to see whether participants have the MEN2 genetic&#xD;
           mutation.&#xD;
&#xD;
        -  Treatment will not be provided as part of this study. However, participants will be&#xD;
           receiving standard care for MTC. They may be eligible for other clinical trials at the&#xD;
           National Institutes of Health.&#xD;
&#xD;
        -  Participants will have regular study visits every 6 to 12 months to evaluate their MTC&#xD;
           and any treatment. Blood tests, imaging studies, and other tests may be performed as&#xD;
           needed to monitor the disease.&#xD;
&#xD;
        -  Participants and their parents/guardians will also complete questionnaires about their&#xD;
           health and emotions during the study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
        -  Medullary Thyroid Carcinoma (MTC) is a calcitonin producing tumor arising from the&#xD;
           parafollicular C cells of thyroid. In children and adults, MTC is usually seen in&#xD;
           association with Multiple Endocrine Neoplasia (MEN) 2A and 2B, which are rare cancer&#xD;
           syndromes resulting from germline mutations of Rearranged during Transfection (RET)&#xD;
           proto-oncogene. MTC develops in virtually all patients with MEN 2, and is the leading&#xD;
           cause of death in these patients. Patients with MEN 2 may have other characteristic&#xD;
           manifestations such as pheochromocytoma and hyperparathyroidism in MEN 2A and&#xD;
           pheochromocytoma, ganglioneuromatosis, and skeletal deformities in MEN 2B.&#xD;
&#xD;
        -  Complete surgical resection is the only current curative treatment for MTC, and the&#xD;
           tumor is unresponsive to standard chemotherapy and conventional doses of radiation&#xD;
           therapy. However, more than half the patients present with advanced or metastatic&#xD;
           disease and cannot be cured surgically. Novel agents are currently under investigation&#xD;
           for treatment of MTC, and vandetanib, an oral RET and receptor tyrosine kinase (RTK)&#xD;
           inhibitor was recently approved by the FDA for adults with advanced or metastatic MTC.&#xD;
           Vandetanib also has activity in children with hereditary MTC.&#xD;
&#xD;
        -  However, complete responses to RTKs have not been observed, and some patients develop&#xD;
           resistance to the treatment with RET and RTK inhibitors or have primary refractory&#xD;
           disease. The natural history of MTC, particularly in patients with MEN 2, the molecular&#xD;
           pathways involved in tumorigenesis, and the development of resistance to targeted&#xD;
           therapies are not well understood.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      -The overall objective of this longitudinal study is to develop a better understanding of the&#xD;
      biology and natural history of MEN2 with or without MTC, particularly in children and adults&#xD;
      with MEN 2A and 2B, as well as study non-tumor manifestations of MEN 2. This will hopefully&#xD;
      allow for developing more effective treatment interventions for tumor and non-tumor related&#xD;
      manifestations, and more sensitive endpoints in clinical trials.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
        -  Patients, must have histologically or cytologically confirmed MTC, confirmed by the&#xD;
           Laboratory of Pathology, NCI or who have MEN2 (regardless of MTC status).&#xD;
&#xD;
        -  Parent or primary caregiver of patient participant (&lt;= 21)&#xD;
&#xD;
        -  Participants may be undergoing standard care or receiving treatment on a clinical trial&#xD;
           while participating in this study.&#xD;
&#xD;
      Design:&#xD;
&#xD;
      This study will allow for longitudinal evaluations of MTC and MEN2 and non-tumor related&#xD;
      manifestations of MEN 2A and 2B in children and adults. Evaluations will consist of the&#xD;
      following (summarized):&#xD;
&#xD;
        1. Clinical and radiological evaluations&#xD;
&#xD;
        2. Detailed pathologic and molecular analysis of tumor specimens will be performed,&#xD;
           including immunohistochemistry (IHC), comparative genomic hybridization (CGH), and&#xD;
           genome sequencing. CGH and genome sequencing will be performd with co-enrollment on&#xD;
           protocol 10-C-0086 Comprehensive Omics Analysis of Pediatric Solid Tumors and&#xD;
           Establishment of a Repository for Related Biological Studies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 30, 2012</start_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>Study growth rate of primary and metastatic tumor lesions</measure>
    <time_frame>5 years</time_frame>
    <description>Characterized features will be described and presented.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Study molecular pathways altered in MTC</measure>
    <time_frame>5 years</time_frame>
    <description>Characterized features will be described and presented.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Describe the non-tumor related manifestations of MEN 2</measure>
    <time_frame>5 years</time_frame>
    <description>Describe the non-tumor related manifestations of MEN 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Investigate the psychosocial experiences</measure>
    <time_frame>5 years</time_frame>
    <description>Investigate the psychosocial experiences</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">216</enrollment>
  <condition>Medullary Thyroid Cancer</condition>
  <arm_group>
    <arm_group_label>Parents/caregivers</arm_group_label>
    <description>Parents or caregivers of study patients to assess their psychosocial experiences and needs.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients</arm_group_label>
    <description>Children and adults with MTC and MEN2B, other non-tumor manifestations of MEN2, and patients with MEN2 who do not demonstrate MTC. Characterize the biology and manifestations of their disease.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with histologically or cytologically confirmed MTC, confirmed by the Laboratory of&#xD;
        Pathology, NCI, or confirmed MEN2A or MEN2B diagnosis, regardless of presence of MTC.&#xD;
        Parents or caregivers of the enrolled patients will also be enrolled.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA FOR PATIENTS:&#xD;
&#xD;
          -  Patients must have histologically or cytologically confirmed MTC, confirmed by the&#xD;
             Laboratory of Pathology, NCI OR Confirmation of MEN2A or MEN2B diagnosis, regardless&#xD;
             of presence of MTC.&#xD;
&#xD;
          -  Performance Status: Ability to travel to the NIH and to undergo evaluations to be&#xD;
             performed on this protocol.&#xD;
&#xD;
          -  Informed Consent: Ability of patient or their legal guardian (if the patient is &lt;18&#xD;
             years old) to understand and willing to sign a written informed consent document.&#xD;
&#xD;
          -  Prior and current therapy: For the purpose of this study subjects who have not&#xD;
             previously received medical or surgical treatment, patients, who have previously&#xD;
             received medical or surgical treatment, and subjects who are currently receiving&#xD;
             medical treatment and/or radiation for MEN 2 related manifestation(s) will be&#xD;
             eligible. Prior and current treatment for MEN 2 related manifestations will be&#xD;
             recorded at trial entry and throughout the study.&#xD;
&#xD;
          -  Patients must have a primary care provider (for example a primary oncologist or&#xD;
             endocrinologist) who can provide and coordinate the medical care for the patient.&#xD;
&#xD;
        EXCLUSION CRITERIA FOR PATIENTS:&#xD;
&#xD;
        -In the opinion of the investigator the patient is not able to return for follow-up visits&#xD;
        or obtain required follow-up studies.&#xD;
&#xD;
        Inclusion Criteria for Parents or Primary Caregivers&#xD;
&#xD;
          -  Must be a parent or primary caregiver of a patient (&lt; 21) who has a histologically or&#xD;
             cytologically confirmed MTC or who have MEN2 (regardless of MTC status).&#xD;
&#xD;
          -  Ability to understand and be willing to sign a written informed consent document.&#xD;
&#xD;
        EXCLUSION CRITERIA FOR PARENTS OR PRIMARY CAREGIVERS: None&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>4 Months</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John W Glod, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Cancer Institute (NCI)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Nicole Lucas</last_name>
    <phone>(240) 760-6252</phone>
    <email>andrea.lucas@nih.gov</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>John W Glod, M.D.</last_name>
    <phone>(240) 760-6194</phone>
    <email>john.glod@nih.gov</email>
  </overall_contact_backup>
  <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>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2012-C-0178.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <verification_date>June 28, 2023</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 9, 2012</study_first_posted>
  <last_update_submitted>August 24, 2023</last_update_submitted>
  <last_update_submitted_qc>August 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Thyroid Tumor</keyword>
  <keyword>Multiple Endocrine Neoplasia 2</keyword>
  <keyword>Pheochromocytoma</keyword>
  <keyword>RET Mutations</keyword>
  <keyword>Natural History</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thyroid Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Neuroendocrine</mesh_term>
    <mesh_term>Thyroid Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>.All IPD recorded in the medical record will be shared with intramural investigators upon request.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Clinical data available during the study and indefinitely.</ipd_time_frame>
    <ipd_access_criteria>Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.</ipd_access_criteria>
  </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/NCT01660984
org study id: 120178
secondary id: 12-C-0178
nct id: NCT01660984
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Background:

      - Medullary thyroid cancer (MTC) is a rare cancer of the thyroid gland. In children and
      adults, it is often part of a condition called Multiple Endocrine Neoplasia 2 (MEN2). MEN2 is
      usually caused by a genetic mutation, and it can cause a number of problems in addition to
      MTC. These problems include adrenal gland tumors, hormone changes, and problems with the
      bones and other organs. Not much is known about how MTC develops over time, especially in
      people with MEN2. Researchers want to study MTC in children and adults and see how it affects
      their growth and development.

      Objectives:

      - To study how medullary thyroid cancer affects children and adults over time.

      Eligibility:

      - Children and adults who have medullary thyroid cancer.

      Design:

        -  Participants will be screened with a brief physical exam and medical history. Blood and
           tissue samples will be collected to see whether participants have the MEN2 genetic
           mutation.

        -  Treatment will not be provided as part of this study. However, participants will be
           receiving standard care for MTC. They may be eligible for other clinical trials at the
           National Institutes of Health.

        -  Participants will have regular study visits every 6 to 12 months to evaluate their MTC
           and any treatment. Blood tests, imaging studies, and other tests may be performed as
           needed to monitor the disease.

        -  Participants and their parents/guardians will also complete questionnaires about their
           health and emotions during the study.
Background:

        -  Medullary Thyroid Carcinoma (MTC) is a calcitonin producing tumor arising from the
           parafollicular C cells of thyroid. In children and adults, MTC is usually seen in
           association with Multiple Endocrine Neoplasia (MEN) 2A and 2B, which are rare cancer
           syndromes resulting from germline mutations of Rearranged during Transfection (RET)
           proto-oncogene. MTC develops in virtually all patients with MEN 2, and is the leading
           cause of death in these patients. Patients with MEN 2 may have other characteristic
           manifestations such as pheochromocytoma and hyperparathyroidism in MEN 2A and
           pheochromocytoma, ganglioneuromatosis, and skeletal deformities in MEN 2B.

        -  Complete surgical resection is the only current curative treatment for MTC, and the
           tumor is unresponsive to standard chemotherapy and conventional doses of radiation
           therapy. However, more than half the patients present with advanced or metastatic
           disease and cannot be cured surgically. Novel agents are currently under investigation
           for treatment of MTC, and vandetanib, an oral RET and receptor tyrosine kinase (RTK)
           inhibitor was recently approved by the FDA for adults with advanced or metastatic MTC.
           Vandetanib also has activity in children with hereditary MTC.

        -  However, complete responses to RTKs have not been observed, and some patients develop
           resistance to the treatment with RET and RTK inhibitors or have primary refractory
           disease. The natural history of MTC, particularly in patients with MEN 2, the molecular
           pathways involved in tumorigenesis, and the development of resistance to targeted
           therapies are not well understood.

      Objectives:

      -The overall objective of this longitudinal study is to develop a better understanding of the
      biology and natural history of MEN2 with or without MTC, particularly in children and adults
      with MEN 2A and 2B, as well as study non-tumor manifestations of MEN 2. This will hopefully
      allow for developing more effective treatment interventions for tumor and non-tumor related
      manifestations, and more sensitive endpoints in clinical trials.

      Eligibility:

        -  Patients, must have histologically or cytologically confirmed MTC, confirmed by the
           Laboratory of Pathology, NCI or who have MEN2 (regardless of MTC status).

        -  Parent or primary caregiver of patient participant (<= 21)

        -  Participants may be undergoing standard care or receiving treatment on a clinical trial
           while participating in this study.

      Design:

      This study will allow for longitudinal evaluations of MTC and MEN2 and non-tumor related
      manifestations of MEN 2A and 2B in children and adults. Evaluations will consist of the
      following (summarized):

        1. Clinical and radiological evaluations

        2. Detailed pathologic and molecular analysis of tumor specimens will be performed,
           including immunohistochemistry (IHC), comparative genomic hybridization (CGH), and
           genome sequencing. CGH and genome sequencing will be performd with co-enrollment on
           protocol 10-C-0086 Comprehensive Omics Analysis of Pediatric Solid Tumors and
           Establishment of a Repository for Related Biological Studies.
observational model: Cohort
time perspective: Prospective
measure: Study growth rate of primary and metastatic tumor lesions
time frame: 5 years
description: Characterized features will be described and presented.
measure: Study molecular pathways altered in MTC
time frame: 5 years
description: Characterized features will be described and presented.
measure: Describe the non-tumor related manifestations of MEN 2
time frame: 5 years
description: Describe the non-tumor related manifestations of MEN 2
measure: Investigate the psychosocial experiences
time frame: 5 years
description: Investigate the psychosocial experiences
arm group label: Parents/caregivers
description: Parents or caregivers of study patients to assess their psychosocial experiences and needs.
arm group label: Patients
description: Children and adults with MTC and MEN2B, other non-tumor manifestations of MEN2, and patients with MEN2 who do not demonstrate MTC. Characterize the biology and manifestations of their disease.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 4 Months
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: John W Glod, M.D.
role: Principal Investigator
affiliation: National Cancer Institute (NCI)
last name: Nicole Lucas
phone: (240) 760-6252
email: andrea.lucas@nih.gov
last name: John W Glod, M.D.
phone: (240) 760-6194
email: john.glod@nih.gov
facility: 
status: Recruiting
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2012-C-0178.html
description: NIH Clinical Center Detailed Web Page
responsible party type: Sponsor
mesh term: Thyroid Neoplasms
mesh term: Carcinoma, Neuroendocrine
mesh term: Thyroid Diseases
sharing ipd: Yes
ipd description: .All IPD recorded in the medical record will be shared with intramural investigators upon request.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Clinical data available during the study and indefinitely.
ipd access criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.