<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/NCT03002623</url>
  </required_header>
  <id_info>
    <org_study_id>170029</org_study_id>
    <secondary_id>17-C-0029</secondary_id>
    <nct_id>NCT03002623</nct_id>
  </id_info>
  <brief_title>CUDC-907 Treatment in People With Metastatic and Locally Advanced Thyroid Cancer</brief_title>
  <official_title>A Phase II Trial of CUDC-907 in Patients With Metastatic and Locally Advanced Thyroid Cancer</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>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      The thyroid is a gland at the base of the throat. Thyroid cancer is a disease that people get&#xD;
      when abnormal cells begin to grow in this gland. Researchers believe a new drug called&#xD;
      CUDC-907 may be able to help people with thyroid cancer that has spread or has gotten worse.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To see if CUDC-907 will shrink tumors in people with advanced thyroid cancer.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      People at least 18 years old who have been diagnosed with locally advanced and metastatic&#xD;
      thyroid cancer.&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will be screened with:&#xD;
&#xD;
      Medical history&#xD;
&#xD;
      Physical exam&#xD;
&#xD;
      Blood and urine tests&#xD;
&#xD;
      Electrocardiogram (ECG) heart test.&#xD;
&#xD;
      Review of their symptoms and how they perform normal activities&#xD;
&#xD;
      A scan will be performed. Some will have a computed tomographic scan (CT) that takes pictures&#xD;
      of the body using a small amount of radiation. Some will have magnetic resonance imaging&#xD;
      (MRI) that uses a magnetic field to take pictures.&#xD;
&#xD;
      Bone scan (some participants)&#xD;
&#xD;
      Fludeoxyglucose (FDG) positron emission tomography (PET) scan to produce a tumor image.&#xD;
&#xD;
      A sample of their tumor from a previous surgery. They may have a biopsy of their tumor if a&#xD;
      tumor sample is not available from a previous surgery.&#xD;
&#xD;
      Participants will be given CUDC-907 in tablet form. They will take it by mouth once a day for&#xD;
      5 days, then take 2 days off, each week.&#xD;
&#xD;
      While taking the study drug, participants will have study visits that repeat the screening&#xD;
      tests.&#xD;
&#xD;
      After they stop treatment, participants will have 3 follow-up visits over a year. They will&#xD;
      repeat some tests. Then participants will be contacted by phone or e-mail every 6 months....&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
        -  There are no standard or effective systemic therapies for metastatic or locally advanced&#xD;
           poorly differentiated and undifferentiated thyroid cancer.&#xD;
&#xD;
        -  Poorly differentiated and undifferentiated thyroid cancer are aggressive, with high&#xD;
           mortality.&#xD;
&#xD;
        -  CUDC-907 is a first-in-class dual inhibitor of histone deacetylase (HDAC) and PI3K&#xD;
           signaling.&#xD;
&#xD;
        -  Approximately 80% of poorly differentiated and undifferentiated thyroid cancers have&#xD;
           driver mutations in the PI3K/AKT pathway or activation of the pathway.&#xD;
&#xD;
        -  HDAC2 is upregulated in poorly differentiated and undifferentiated thyroid cancer, and&#xD;
           aggressive variants of differentiated thyroid cancer, and CUDC-907 treatment reduces&#xD;
           HDAC2 levels in thyroid cancer cells.&#xD;
&#xD;
        -  CUDC-907 inhibits thyroid cancer cell growth, invasion and migration in vitro.&#xD;
&#xD;
        -  In addition to inhibiting the PI3K/AKT signaling pathway, CUDC-907 inhibits the&#xD;
           EGFR/RAS/RAF/MEK/ERK signaling pathway, which is also activated in poorly differentiated&#xD;
           and undifferentiated thyroid cancer.&#xD;
&#xD;
        -  CUDC-907 inhibits growth and metastases in a mouse model of metastatic thyroid cancer.&#xD;
&#xD;
        -  We hypothesize that CUDC-907 will cause cancer regression in patients with metastatic&#xD;
           and locally advanced poorly differentiated and undifferentiated thyroid cancer, and&#xD;
           aggressive variants of differentiated thyroid cancer.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      -To determine response to CUDC-907 treatment by Response Evaluation Criteria in Solid Tumors&#xD;
      (RECIST) criteria in patients with locally advanced and metastatic poorly differentiated and&#xD;
      undifferentiated thyroid cancer, and aggressive variants of differentiated thyroid cancer.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
        -  Age greater than or equal to 18 years&#xD;
&#xD;
        -  Thyroid cancer that is refractory to or relapsed after standard treatment.&#xD;
&#xD;
        -  Aggressive thyroid cancer confirmed on histology or cytologic analysis.&#xD;
&#xD;
        -  Measurable disease.&#xD;
&#xD;
        -  Last dose of chemotherapy or last radiotherapy treatment more than 4 weeks prior to&#xD;
           starting treatment with this protocol, except for subjects with&#xD;
           anaplastic/undifferentiated thyroid cancer who may enroll immediately after&#xD;
           discontinuation of previous therapy.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Open label, phase II trial to determine response to CUDC-907 treatment.&#xD;
&#xD;
        -  Patients will be given 60 mg of CUDC-907 orally for 5 consecutive days followed by 2&#xD;
           days off (5/2 schedule).&#xD;
&#xD;
        -  One cycle is 21 days. Patients may continue on treatment if there is no disease&#xD;
           progression.&#xD;
&#xD;
        -  Initial anatomic and functional imaging will be performed at enrollment and after 2&#xD;
           cycles of treatment. Thereafter, anatomic imaging will be performed every two cycles of&#xD;
           treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study was closed because investigator left the National Institutes of Health.&#xD;
  </why_stopped>
  <start_date type="Actual">December 22, 2016</start_date>
  <completion_date type="Actual">February 12, 2018</completion_date>
  <primary_completion_date type="Actual">February 12, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This is a single group assignment. All patients regardless of subtype of thyroid cancer received one single treatment and follow up plan with option to continue the treatment when scan was negative.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With a Clinical Response (Complete Response (CR) + Partial Response (PR)) Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1</measure>
    <time_frame>Approximately 6 months</time_frame>
    <description>Clinical response, defined as a complete response + partial response (CR+PR) to CUDC-907 treatment, was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. Partial response is at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Median Amount of Time Subject Survives Without Disease Progression After Treatment</measure>
    <time_frame>Approximately 6 months</time_frame>
    <description>Time in days from initiation of treatment until tumor grows more than 20%. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Amount of Time Subject Survives After Therapy</measure>
    <time_frame>Approximately 12 months</time_frame>
    <description>Time in days from the initiation of treatment until death estimated by the Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation Between Mutation Status of Tumor and Median Amount of Time Subject Survives Without Disease Progression After Treatment</measure>
    <time_frame>At disease progression</time_frame>
    <description>The amount of time subject survives without disease progression is compared by patient tumor mutation status.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation Between Activation of the Phosphoinositide 3-kinase (PI3K)/Protein Kinase B (AKT) and EGFR/RAS/RAF/MEK/ERK Pathways in Tumor Tissue and Median Amount of Time Subject Survives Without Disease Progression After Treatment</measure>
    <time_frame>At disease progression</time_frame>
    <description>The amount of time subject survives without disease progression is compared by the protein levels of PI3K/AKT and epidermal growth factor receptor (EGFR)/rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/methyl ethyl ketone (MEK)/extracellular-signal regulated kinase (ERK) in tumor tissue.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation Between Histone Deacetylase 2 (HDAC2) and Survivin Protein Levels in Tumor Tissue With Median Amount of Time Subject Survives Without Disease Progression After Treatment</measure>
    <time_frame>At disease progression</time_frame>
    <description>The amount of time subject survives without disease progression is compared by the protein levels of HDAC2 and surviving in tumor tissue. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)</measure>
    <time_frame>Date treatment consent signed to date off study, approximately 12 months and 13 days</time_frame>
    <description>Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Thyroid Neoplasms</condition>
  <condition>Poorly Differentiated and Undifferentiated Thyroid Cancer</condition>
  <condition>Differentiated Thyroid Cancer</condition>
  <arm_group>
    <arm_group_label>Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CUDC-907 for thyroid cancer</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CUDC-907</intervention_name>
    <description>60 mg (2 capsules of 30 mg capsules) will be given orally once a day 5 days on and 2 days off.</description>
    <arm_group_label>Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
          -  Subjects greater than or equal to 18 years of age.&#xD;
&#xD;
          -  Thyroid cancer histology or cytology that is aggressive (anaplastic/undifferentiated&#xD;
             thyroid cancer, poorly differentiated thyroid cancer, Hurthle cell carcinoma,&#xD;
             tall-cell variant of papillary thyroid cancer, sclerosing variant of papillary thyroid&#xD;
             cancer).&#xD;
&#xD;
          -  Measurable disease.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.&#xD;
&#xD;
          -  Absolute neutrophil count greater than or equal to 1,000/microL&#xD;
&#xD;
          -  Platelets greater than or equal to 75,000/microL&#xD;
&#xD;
          -  Creatinine less than or equal to 1.5 times upper limit of normal (ULN) or creatinine&#xD;
             clearance &gt; 60ml for patients with creatinine levels 1.5 times above institutional ULN&#xD;
             (calculated based on age, weight and sex&#xD;
&#xD;
          -  Total bilirubin less than or equal to 1.5 times ULN; aspartate aminotransferase&#xD;
             (AST)/alanine aminotransferase (ALT) less than or equal to 2.5 times ULN. For subjects&#xD;
             with documented liver metastases, the AST/ALT may be less than or equal to 5 times&#xD;
             ULN.&#xD;
&#xD;
          -  Recovery to Grade 1 or baseline of any toxicity due to prior anticancer therapies&#xD;
             (excluding alopecia).&#xD;
&#xD;
          -  Platelet transfusions to help patients meet eligibility criteria are not allowed&#xD;
             within 3 days prior to screening complete blood count (CBC) or Cycle 1, Day 1&#xD;
             treatment.&#xD;
&#xD;
          -  Women of child bearing potential must have a negative serum pregnancy test.&#xD;
&#xD;
          -  The effects of CUDC-907 on the developing human fetus are unknown. For this reason,&#xD;
             women of child-bearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control; abstinence) prior to study entry, for&#xD;
             the duration of study participation and for 30 days following the last study&#xD;
             treatment.&#xD;
&#xD;
        Should a woman become pregnant or suspect she is pregnant while she or her partner is&#xD;
        participating in this study, she should inform her treating physician immediately.&#xD;
&#xD;
        -Able to provide written informed consent and to follow protocol requirements.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          -  Systemic anticancer therapy within 4 weeks of study entry, except for subjects with&#xD;
             anaplastic/undifferentiated thyroid cancer who may be enrolled immediately after&#xD;
             discontinuation of previous therapy.&#xD;
&#xD;
          -  Other investigational agents within 4 weeks prior to study treatment except for&#xD;
             subjects with anaplastic/undifferentiated thyroid cancer who may be enrolled&#xD;
             immediately of discontinuation of previous therapy.&#xD;
&#xD;
          -  Pregnant women are excluded from this study because the potential risk of teratogenic&#xD;
             or abortifacient effects of CUDC-907 is unknown. Because there is an unknown but&#xD;
             potential risk for adverse events in nursing infants secondary to treatment of the&#xD;
             mother with CUDC-907, breastfeeding should be discontinued if the mother is treated&#xD;
             with CUDC-907. These potential risks may also apply to other agents used in this&#xD;
             study.&#xD;
&#xD;
          -  Diabetes mellitus that is not controlled with medication.&#xD;
&#xD;
          -  Serious infection requiring intravenous antibiotic therapy within 14 days prior to&#xD;
             study treatment.&#xD;
&#xD;
          -  Evidence of central nervous system metastasis.&#xD;
&#xD;
          -  Uncontrolled or severe cardiovascular disease, including myocardial infarction,&#xD;
             unstable angina, or atrial fibrillation (AFib) within 6 months prior to study&#xD;
             treatment, New York Heart Association (NYHA) Class II or greater congestive heart&#xD;
             failure, serious arrhythmias requiring medication for treatment, clinically&#xD;
             significant pericardial disease, cardiac amyloidosis, or corrected QT interval (QTc)&#xD;
             with Fridericia's (QTcF) correction that is unmeasurable or greater than or equal to&#xD;
             480 msec on screening electrocardiogram (ECG). (Note: for QTcF greater than or equal&#xD;
             to 480 sec on the screening ECG, the ECG may be repeated twice at least 24 hours&#xD;
             apart; the mean QTcF from the three screening ECGs must be &lt; 480 msec in order to meet&#xD;
             eligibility for trial participation).&#xD;
&#xD;
          -  Gastrointestinal disease or disorder that could interfere with the swallowing, oral&#xD;
             absorption, or tolerance of CUDC-907. This includes uncontrolled diarrhea (&gt; 1 watery&#xD;
             stool/day), major abdominal surgery, significant bowel obstruction and/or&#xD;
             gastrointestinal diseases that could alter the assessment of pharmacokinetics or&#xD;
             safety, including but not limited to: irritable bowel syndrome, ulcerative colitis,&#xD;
             Crohn's disease and hemorrhagic coloproctitis.&#xD;
&#xD;
          -  Unstable or clinically significant concurrent medical condition that would, in the&#xD;
             opinion of the investigator, jeopardize the safety of a subject and/or compliance with&#xD;
             the protocol.&#xD;
&#xD;
          -  Second primary malignancy within 2 years of study entry other than adequately treated&#xD;
             non-melanoma skin or superficial bladder cancer, curatively treated carcinoma in situ&#xD;
             of the cervix or other curatively treated solid tumor deemed by the investigator to be&#xD;
             at low risk for recurrence.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Naris Nilubol, 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?B_2017-C-0029.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <reference>
    <citation>Simon D, Koehrle J, Reiners C, Boerner AR, Schmutzler C, Mainz K, Goretzki PE, Roeher HD. Redifferentiation therapy with retinoids: therapeutic option for advanced follicular and papillary thyroid carcinoma. World J Surg. 1998 Jun;22(6):569-74. doi: 10.1007/s002689900436.</citation>
    <PMID>9597930</PMID>
  </reference>
  <reference>
    <citation>Nilubol N, Kebebew E. Should small papillary thyroid cancer be observed? A population-based study. Cancer. 2015 Apr 1;121(7):1017-24. doi: 10.1002/cncr.29123. Epub 2014 Nov 25.</citation>
    <PMID>25425528</PMID>
  </reference>
  <reference>
    <citation>Kebebew E, Greenspan FS, Clark OH, Woeber KA, McMillan A. Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors. Cancer. 2005 Apr 1;103(7):1330-5. doi: 10.1002/cncr.20936.</citation>
    <PMID>15739211</PMID>
  </reference>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 22, 2016</study_first_submitted>
  <study_first_submitted_qc>December 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 26, 2016</study_first_posted>
  <results_first_submitted>July 27, 2018</results_first_submitted>
  <results_first_submitted_qc>December 18, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">December 21, 2018</results_first_posted>
  <last_update_submitted>December 18, 2018</last_update_submitted>
  <last_update_submitted_qc>December 18, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 21, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Institutes of Health Clinical Center (CC)</investigator_affiliation>
    <investigator_full_name>Naris Nilubol, M.D.</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Dual Inhibitor of HDAC and P13K Signaling</keyword>
  <keyword>HDAC2</keyword>
  <keyword>EGFR/RAS/RAF/MEK/ERK Signaling Pathway Inhibition</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thyroid Neoplasms</mesh_term>
    <mesh_term>Thyroid Carcinoma, Anaplastic</mesh_term>
    <mesh_term>Thyroid Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 13, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/23/NCT03002623/Prot_SAP_ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Anaplastic Thyroid Cancer</title>
          <description>CUDC-907 for anaplastic thyroid cancer&#xD;
CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.</description>
        </group>
        <group group_id="P2">
          <title>Poorly Differentiated/Variants of Thyroid Cancer</title>
          <description>CUDC-907 for Poorly differentiated and aggressive variants of differentiated thyroid cancer.&#xD;
CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Anaplastic Thyroid Cancer</title>
          <description>CUDC-907 for anaplastic thyroid cancer CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.</description>
        </group>
        <group group_id="B2">
          <title>Poorly Differentiated/Variants of Thyroid Cancer</title>
          <description>CUDC-907 for Poorly differentiated and aggressive variants of differentiated thyroid cancer.&#xD;
CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="4"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="7"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.5" spread="19.18"/>
                    <measurement group_id="B2" value="66.6" spread="1.39"/>
                    <measurement group_id="B3" value="62.5" spread="16.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Mexican, Puerto Rican, Cuban, Central/So American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not meeting definition for Hispanic or Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With a Clinical Response (Complete Response (CR) + Partial Response (PR)) Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1</title>
        <description>Clinical response, defined as a complete response + partial response (CR+PR) to CUDC-907 treatment, was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. Partial response is at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.</description>
        <time_frame>Approximately 6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Anaplastic Thyroid Cancer</title>
            <description>CUDC-907 for anaplastic thyroid cancer CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.</description>
          </group>
          <group group_id="O2">
            <title>Poorly Differentiated/Variants of Thyroid Cancer</title>
            <description>CUDC-907 for Poorly differentiated and aggressive variants of differentiated thyroid cancer.&#xD;
CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With a Clinical Response (Complete Response (CR) + Partial Response (PR)) Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1</title>
          <description>Clinical response, defined as a complete response + partial response (CR+PR) to CUDC-907 treatment, was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. Partial response is at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Complete Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Partial Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Amount of Time Subject Survives Without Disease Progression After Treatment</title>
        <description>Time in days from initiation of treatment until tumor grows more than 20%. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions.</description>
        <time_frame>Approximately 6 months</time_frame>
        <population>One participant was non-evaluable (withdrew consent).</population>
        <group_list>
          <group group_id="O1">
            <title>Anaplastic Thyroid Cancer</title>
            <description>CUDC-907 for anaplastic thyroid cancer CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.</description>
          </group>
          <group group_id="O2">
            <title>Poorly Differentiated/Variants of Thyroid Cancer</title>
            <description>CUDC-907 for Poorly differentiated and aggressive variants of differentiated thyroid cancer.&#xD;
CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.</description>
          </group>
        </group_list>
        <measure>
          <title>Median Amount of Time Subject Survives Without Disease Progression After Treatment</title>
          <description>Time in days from initiation of treatment until tumor grows more than 20%. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions.</description>
          <population>One participant was non-evaluable (withdrew consent).</population>
          <units>Days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.3" lower_limit="21" upper_limit="45"/>
                    <measurement group_id="O2" value="147" lower_limit="127" upper_limit="167"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Amount of Time Subject Survives After Therapy</title>
        <description>Time in days from the initiation of treatment until death estimated by the Kaplan-Meier method.</description>
        <time_frame>Approximately 12 months</time_frame>
        <population>Participants are grouped together because of a small sample size and not enough power to compare the difference between two groups. No statistical analysis to be done.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>CUDC-907 for anaplastic thyroid cancer CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.&#xD;
CUDC-907 for Poorly differentiated and aggressive variants of differentiated thyroid cancer.&#xD;
CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.</description>
          </group>
        </group_list>
        <measure>
          <title>Median Amount of Time Subject Survives After Therapy</title>
          <description>Time in days from the initiation of treatment until death estimated by the Kaplan-Meier method.</description>
          <population>Participants are grouped together because of a small sample size and not enough power to compare the difference between two groups. No statistical analysis to be done.</population>
          <units>Days</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="127" lower_limit="66.5" upper_limit="187.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Correlation Between Mutation Status of Tumor and Median Amount of Time Subject Survives Without Disease Progression After Treatment</title>
        <description>The amount of time subject survives without disease progression is compared by patient tumor mutation status.</description>
        <time_frame>At disease progression</time_frame>
        <population>This outcome measure was not done. Data was collected but the correlation between mutation status of tumor and progression-free survival was not performed because of only BRAF V600E and the loss of tumor protein 53 (TP53) heterozygosity were found on a single patient each. Since only 1 mutant was found for each, no analysis was done.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>CUDC-907 for anaplastic thyroid cancer CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.&#xD;
CUDC-907 for Poorly differentiated and aggressive variants of differentiated thyroid cancer.&#xD;
CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.</description>
          </group>
        </group_list>
        <measure>
          <title>Correlation Between Mutation Status of Tumor and Median Amount of Time Subject Survives Without Disease Progression After Treatment</title>
          <description>The amount of time subject survives without disease progression is compared by patient tumor mutation status.</description>
          <population>This outcome measure was not done. Data was collected but the correlation between mutation status of tumor and progression-free survival was not performed because of only BRAF V600E and the loss of tumor protein 53 (TP53) heterozygosity were found on a single patient each. Since only 1 mutant was found for each, no analysis was done.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Correlation Between Activation of the Phosphoinositide 3-kinase (PI3K)/Protein Kinase B (AKT) and EGFR/RAS/RAF/MEK/ERK Pathways in Tumor Tissue and Median Amount of Time Subject Survives Without Disease Progression After Treatment</title>
        <description>The amount of time subject survives without disease progression is compared by the protein levels of PI3K/AKT and epidermal growth factor receptor (EGFR)/rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/methyl ethyl ketone (MEK)/extracellular-signal regulated kinase (ERK) in tumor tissue.</description>
        <time_frame>At disease progression</time_frame>
        <population>This outcome measure was not done. Data was collected but no samples were analyzed because the experiment was not technically successful due to inconclusive results from immunohistochemistry (study of protein levels in tumor tissue) analysis of P13K/AKT and EGFR/RAS/RAF/MEK/ERK proteins.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>CUDC-907 for anaplastic thyroid cancer CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.&#xD;
CUDC-907 for Poorly differentiated and aggressive variants of differentiated thyroid cancer.&#xD;
CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.</description>
          </group>
        </group_list>
        <measure>
          <title>Correlation Between Activation of the Phosphoinositide 3-kinase (PI3K)/Protein Kinase B (AKT) and EGFR/RAS/RAF/MEK/ERK Pathways in Tumor Tissue and Median Amount of Time Subject Survives Without Disease Progression After Treatment</title>
          <description>The amount of time subject survives without disease progression is compared by the protein levels of PI3K/AKT and epidermal growth factor receptor (EGFR)/rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/methyl ethyl ketone (MEK)/extracellular-signal regulated kinase (ERK) in tumor tissue.</description>
          <population>This outcome measure was not done. Data was collected but no samples were analyzed because the experiment was not technically successful due to inconclusive results from immunohistochemistry (study of protein levels in tumor tissue) analysis of P13K/AKT and EGFR/RAS/RAF/MEK/ERK proteins.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Correlation Between Histone Deacetylase 2 (HDAC2) and Survivin Protein Levels in Tumor Tissue With Median Amount of Time Subject Survives Without Disease Progression After Treatment</title>
        <description>The amount of time subject survives without disease progression is compared by the protein levels of HDAC2 and surviving in tumor tissue. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions.</description>
        <time_frame>At disease progression</time_frame>
        <population>This outcome measure was not done. Data was collected but not analyzed because the assessment of HDAC2 and survivin proteins cannot be reliably performed with consistent results.</population>
        <group_list>
          <group group_id="O1">
            <title>Anaplastic Cancer</title>
            <description>CUDC-907 for anaplastic thyroid cancer CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.</description>
          </group>
        </group_list>
        <measure>
          <title>Correlation Between Histone Deacetylase 2 (HDAC2) and Survivin Protein Levels in Tumor Tissue With Median Amount of Time Subject Survives Without Disease Progression After Treatment</title>
          <description>The amount of time subject survives without disease progression is compared by the protein levels of HDAC2 and surviving in tumor tissue. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions.</description>
          <population>This outcome measure was not done. Data was collected but not analyzed because the assessment of HDAC2 and survivin proteins cannot be reliably performed with consistent results.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)</title>
        <description>Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
        <time_frame>Date treatment consent signed to date off study, approximately 12 months and 13 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Anaplastic Thyroid Cancer</title>
            <description>CUDC-907 for anaplastic thyroid cancer CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.</description>
          </group>
          <group group_id="O2">
            <title>Poorly Differentiated/Variants of Thyroid Cancer</title>
            <description>CUDC-907 for Poorly differentiated and aggressive variants of differentiated thyroid cancer.&#xD;
CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.</description>
          </group>
        </group_list>
        <measure>
          <title>Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)</title>
          <description>Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Date treatment consent signed to date off study, approximately 12 months and 13 days.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Anaplastic Thyroid Cancer</title>
          <description>CUDC-907 for anaplastic thyroid cancer CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.</description>
        </group>
        <group group_id="E2">
          <title>Poorly Differentiated/Variants of Thyroid Cancer</title>
          <description>CUDC-907 for Poorly differentiated and aggressive variants of differentiated thyroid cancer.&#xD;
CUDC-907: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day, 5 days on and 2 days off.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle weakness lower limb</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Tumor pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Naris Nilubol</name_or_title>
      <organization>National Cancer Institute</organization>
      <phone>301- 451-2355</phone>
      <email>niluboln@nih.gov</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03002623
org study id: 170029
secondary id: 17-C-0029
nct id: NCT03002623
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Background:

      The thyroid is a gland at the base of the throat. Thyroid cancer is a disease that people get
      when abnormal cells begin to grow in this gland. Researchers believe a new drug called
      CUDC-907 may be able to help people with thyroid cancer that has spread or has gotten worse.

      Objective:

      To see if CUDC-907 will shrink tumors in people with advanced thyroid cancer.

      Eligibility:

      People at least 18 years old who have been diagnosed with locally advanced and metastatic
      thyroid cancer.

      Design:

      Participants will be screened with:

      Medical history

      Physical exam

      Blood and urine tests

      Electrocardiogram (ECG) heart test.

      Review of their symptoms and how they perform normal activities

      A scan will be performed. Some will have a computed tomographic scan (CT) that takes pictures
      of the body using a small amount of radiation. Some will have magnetic resonance imaging
      (MRI) that uses a magnetic field to take pictures.

      Bone scan (some participants)

      Fludeoxyglucose (FDG) positron emission tomography (PET) scan to produce a tumor image.

      A sample of their tumor from a previous surgery. They may have a biopsy of their tumor if a
      tumor sample is not available from a previous surgery.

      Participants will be given CUDC-907 in tablet form. They will take it by mouth once a day for
      5 days, then take 2 days off, each week.

      While taking the study drug, participants will have study visits that repeat the screening
      tests.

      After they stop treatment, participants will have 3 follow-up visits over a year. They will
      repeat some tests. Then participants will be contacted by phone or e-mail every 6 months....
Background:

        -  There are no standard or effective systemic therapies for metastatic or locally advanced
           poorly differentiated and undifferentiated thyroid cancer.

        -  Poorly differentiated and undifferentiated thyroid cancer are aggressive, with high
           mortality.

        -  CUDC-907 is a first-in-class dual inhibitor of histone deacetylase (HDAC) and PI3K
           signaling.

        -  Approximately 80% of poorly differentiated and undifferentiated thyroid cancers have
           driver mutations in the PI3K/AKT pathway or activation of the pathway.

        -  HDAC2 is upregulated in poorly differentiated and undifferentiated thyroid cancer, and
           aggressive variants of differentiated thyroid cancer, and CUDC-907 treatment reduces
           HDAC2 levels in thyroid cancer cells.

        -  CUDC-907 inhibits thyroid cancer cell growth, invasion and migration in vitro.

        -  In addition to inhibiting the PI3K/AKT signaling pathway, CUDC-907 inhibits the
           EGFR/RAS/RAF/MEK/ERK signaling pathway, which is also activated in poorly differentiated
           and undifferentiated thyroid cancer.

        -  CUDC-907 inhibits growth and metastases in a mouse model of metastatic thyroid cancer.

        -  We hypothesize that CUDC-907 will cause cancer regression in patients with metastatic
           and locally advanced poorly differentiated and undifferentiated thyroid cancer, and
           aggressive variants of differentiated thyroid cancer.

      Objective:

      -To determine response to CUDC-907 treatment by Response Evaluation Criteria in Solid Tumors
      (RECIST) criteria in patients with locally advanced and metastatic poorly differentiated and
      undifferentiated thyroid cancer, and aggressive variants of differentiated thyroid cancer.

      Eligibility:

        -  Age greater than or equal to 18 years

        -  Thyroid cancer that is refractory to or relapsed after standard treatment.

        -  Aggressive thyroid cancer confirmed on histology or cytologic analysis.

        -  Measurable disease.

        -  Last dose of chemotherapy or last radiotherapy treatment more than 4 weeks prior to
           starting treatment with this protocol, except for subjects with
           anaplastic/undifferentiated thyroid cancer who may enroll immediately after
           discontinuation of previous therapy.

      Design:

        -  Open label, phase II trial to determine response to CUDC-907 treatment.

        -  Patients will be given 60 mg of CUDC-907 orally for 5 consecutive days followed by 2
           days off (5/2 schedule).

        -  One cycle is 21 days. Patients may continue on treatment if there is no disease
           progression.

        -  Initial anatomic and functional imaging will be performed at enrollment and after 2
           cycles of treatment. Thereafter, anatomic imaging will be performed every two cycles of
           treatment.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This is a single group assignment. All patients regardless of subtype of thyroid cancer received one single treatment and follow up plan with option to continue the treatment when scan was negative.
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With a Clinical Response (Complete Response (CR) + Partial Response (PR)) Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
time frame: Approximately 6 months
description: Clinical response, defined as a complete response + partial response (CR+PR) to CUDC-907 treatment, was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response is at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.
measure: Median Amount of Time Subject Survives Without Disease Progression After Treatment
time frame: Approximately 6 months
description: Time in days from initiation of treatment until tumor grows more than 20%. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions.
measure: Median Amount of Time Subject Survives After Therapy
time frame: Approximately 12 months
description: Time in days from the initiation of treatment until death estimated by the Kaplan-Meier method.
measure: Correlation Between Mutation Status of Tumor and Median Amount of Time Subject Survives Without Disease Progression After Treatment
time frame: At disease progression
description: The amount of time subject survives without disease progression is compared by patient tumor mutation status.
measure: Correlation Between Activation of the Phosphoinositide 3-kinase (PI3K)/Protein Kinase B (AKT) and EGFR/RAS/RAF/MEK/ERK Pathways in Tumor Tissue and Median Amount of Time Subject Survives Without Disease Progression After Treatment
time frame: At disease progression
description: The amount of time subject survives without disease progression is compared by the protein levels of PI3K/AKT and epidermal growth factor receptor (EGFR)/rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/methyl ethyl ketone (MEK)/extracellular-signal regulated kinase (ERK) in tumor tissue.
measure: Correlation Between Histone Deacetylase 2 (HDAC2) and Survivin Protein Levels in Tumor Tissue With Median Amount of Time Subject Survives Without Disease Progression After Treatment
time frame: At disease progression
description: The amount of time subject survives without disease progression is compared by the protein levels of HDAC2 and surviving in tumor tissue. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions.
measure: Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)
time frame: Date treatment consent signed to date off study, approximately 12 months and 13 days
description: Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
arm group label: Group
arm group type: Experimental
description: CUDC-907 for thyroid cancer
intervention type: Drug
intervention name: CUDC-907
description: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day 5 days on and 2 days off.
arm group label: Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Naris Nilubol, M.D.
role: Principal Investigator
affiliation: National Cancer Institute (NCI)
facility: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2017-C-0029.html
description: NIH Clinical Center Detailed Web Page
citation: Simon D, Koehrle J, Reiners C, Boerner AR, Schmutzler C, Mainz K, Goretzki PE, Roeher HD. Redifferentiation therapy with retinoids: therapeutic option for advanced follicular and papillary thyroid carcinoma. World J Surg. 1998 Jun;22(6):569-74. doi: 10.1007/s002689900436.
PMID: 9597930
citation: Nilubol N, Kebebew E. Should small papillary thyroid cancer be observed? A population-based study. Cancer. 2015 Apr 1;121(7):1017-24. doi: 10.1002/cncr.29123. Epub 2014 Nov 25.
PMID: 25425528
citation: Kebebew E, Greenspan FS, Clark OH, Woeber KA, McMillan A. Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors. Cancer. 2005 Apr 1;103(7):1330-5. doi: 10.1002/cncr.20936.
PMID: 15739211
responsible party type: Principal Investigator
investigator affiliation: National Institutes of Health Clinical Center (CC)
investigator full name: Naris Nilubol, M.D.
investigator title: Principal Investigator
mesh term: Thyroid Neoplasms
mesh term: Thyroid Carcinoma, Anaplastic
mesh term: Thyroid Diseases
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 