<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/NCT01709292</url>
  </required_header>
  <id_info>
    <org_study_id>2012-0471</org_study_id>
    <secondary_id>NCI-2012-02171</secondary_id>
    <nct_id>NCT01709292</nct_id>
  </id_info>
  <brief_title>Vemurafenib Neoadjuvant Trial in Locally Advanced Thyroid Cancer</brief_title>
  <official_title>Pharmacodynamic Study of Vemurafenib in the Neoadjuvant Setting in Patients With Locally Advanced Thyroid Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</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>
      The goal of this clinical research study is to learn about how vemurafenib may affect certain&#xD;
      biomarkers in patients with PTC. Biomarkers are in the blood/tissue and may be related to&#xD;
      your reaction to the study drug. The safety of this drug will also be studied.&#xD;
&#xD;
      Vemurafenib is designed to block the BRAF gene mutation. This mutation causes cancer and&#xD;
      cancer growth. By blocking this mutation, the drug may kill the cancer cells with the&#xD;
      mutation and/or stop the tumor from growing.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Drug Administration and Groups:&#xD;
&#xD;
      If you are found to be eligible to take part in this study, you will take 4 tablets of&#xD;
      vemurafenib by mouth 2 times each day for 56 days. You should take each dose about 12 hours&#xD;
      apart. If you miss taking the drug at a scheduled time by more than 4 hours, you should skip&#xD;
      that dose and wait until the next dose.&#xD;
&#xD;
      After 56 days, the treatment you receive will depend on what group you are assigned to:&#xD;
&#xD;
        -  If the disease has spread outside the neck, you will be in Group A.&#xD;
&#xD;
        -  If the disease is able to be entirely removed through surgery, you will be in Group B.&#xD;
&#xD;
        -  If the disease is unable to be operated on, you will be in Group C.&#xD;
&#xD;
      Study Visits:&#xD;
&#xD;
      At all visits, you will be asked about any side effects you may be having and about any other&#xD;
      drugs you may be taking.&#xD;
&#xD;
      Before you take the study drug (Baseline):&#xD;
&#xD;
        -  You will have a procedure called a laryngoscopy, in which a tube with a small camera in&#xD;
           inserted into the nose to inspect your sinus, throat, and voice box.&#xD;
&#xD;
        -  You will have a colonoscopy if you have a history of abnormal growth in the bowel&#xD;
           (polyps or colon cancer). During this procedure a tube with a small camera is inserted&#xD;
           in the anus to inspect your large bowel.&#xD;
&#xD;
      At Day 28:&#xD;
&#xD;
        -  You will have a physical exam, including measurement of your vital signs.&#xD;
&#xD;
        -  Your performance status will be recorded.&#xD;
&#xD;
        -  You will have an EKG.&#xD;
&#xD;
        -  Blood (about 1 tablespoon) will be drawn for routine tests.&#xD;
&#xD;
      Within 1 week before Day 56, you will have CT scans of the neck, chest, and abdomen to check&#xD;
      the status of the disease.&#xD;
&#xD;
      At Day 56, if you are in Group A or B, you will have surgery to remove the tumor. You will&#xD;
      sign a separate consent form that describes this surgery and its risks. If you are in Group&#xD;
      C, you will have a core biopsy. During the surgery/biopsy, blood (about 1 teaspoon) will also&#xD;
      be collected for biomarker testing.&#xD;
&#xD;
      Follow-Up:&#xD;
&#xD;
      Your follow-up after the surgery/biopsy will depend on which study group you are in.&#xD;
&#xD;
      Groups A and C:&#xD;
&#xD;
      If you are in Group A, you will stop taking the study drug for about 2-4 weeks after you have&#xD;
      surgery. If you are in Group C, you will not stop taking the study drug. Every 4 weeks (after&#xD;
      you resume taking the study drug if you are in Group A, and after the biopsy if you are in&#xD;
      Group C):&#xD;
&#xD;
        -  You will have a physical exam, including measurement of your vital signs and a skin&#xD;
           exam.&#xD;
&#xD;
        -  Your performance status will be recorded.&#xD;
&#xD;
        -  Blood (about 1 tablespoon) will be drawn for routine tests.&#xD;
&#xD;
        -  You will be asked about any other drugs you may be taking and about any side effects you&#xD;
           may be having.&#xD;
&#xD;
        -  If you are in Group A, these tests will also be performed the day you start taking the&#xD;
           study drug again. You will also have an EKG.&#xD;
&#xD;
      Additionally, every 8 weeks (if you are in Group A or C), you will have CT scans of the neck,&#xD;
      chest, and abdomen to check the status of the disease. Blood (about 1 teaspoon) will also be&#xD;
      drawn for biomarker testing at the first of these visits.&#xD;
&#xD;
      About 1 year after your laryngoscopy and colonoscopy, these procedures will be performed&#xD;
      again to check for side effects related to the study drug. If you did not receive a baseline&#xD;
      colonoscopy, this procedure will be performed about 1 year after starting vemurafenib. If you&#xD;
      continue on study drug for more than a year, you will have a laryngoscopy every 12 months.&#xD;
&#xD;
      At any time the study doctor thinks it is needed, you will have a colonoscopy and&#xD;
      laryngoscopy.&#xD;
&#xD;
      About 1 year after the surgery/biopsy, you will return to clinic to check if the disease has&#xD;
      come back. At this visit, you will have a CT scan or ultrasound of the neck, and blood (about&#xD;
      1 tablespoon) will be drawn for tests of your thyroid function.&#xD;
&#xD;
      If after 4 months the study doctor thinks it is in your best interest, you will only need to&#xD;
      have study visits every 8 weeks. You will still have blood (about 1 tablespoon) drawn for&#xD;
      routine tests at a local lab and you will be called by the study staff to check on you. Each&#xD;
      call will last about 5-10 minutes.&#xD;
&#xD;
      If you are in Group C, and if during follow-up the study doctor decides that the disease can&#xD;
      be operated on, you will be crossed over to Group A or B. You will have surgery and have the&#xD;
      follow-up visits described for that study group.&#xD;
&#xD;
      Group B:&#xD;
&#xD;
      If you are in Group B, you will have a follow-up visit about 2 weeks after surgery. The&#xD;
      following tests and procedures will be performed:&#xD;
&#xD;
        -  You will have a physical exam, including measurement of your vital signs.&#xD;
&#xD;
        -  Your performance status will be recorded.&#xD;
&#xD;
        -  Blood (about 1 tablespoon) will be drawn for routine tests.&#xD;
&#xD;
        -  You will be asked about any other drugs you may be taking and about any side effects you&#xD;
           may be having.&#xD;
&#xD;
      You will have a second follow-up visit about 8 weeks after surgery. You will have a CT scan&#xD;
      of the neck to check the status of the disease. You will have the option of continuing to&#xD;
      receive vemurafenib if your doctor thinks it is in your best interest. If you do continue on&#xD;
      vemurafenib, you will follow the Group A follow-up schedule (above).&#xD;
&#xD;
      About 1 year after your laryngoscopy and colonoscopy, these procedures will be performed&#xD;
      again to check for side effects related to the study drug. If you did not receive a baseline&#xD;
      colonoscopy, this procedure will be performed about 1 year after starting vemurafenib.&#xD;
&#xD;
      At any time the study doctor thinks it is needed, you will have a colonoscopy and&#xD;
      laryngoscopy.&#xD;
&#xD;
      About 1 year after the surgery/biopsy, you will return to clinic to check if the disease has&#xD;
      come back. At this visit, you will have a CT scan or ultrasound of the neck, and blood (about&#xD;
      1 tablespoon) will be drawn for tests of your thyroid function.&#xD;
&#xD;
      Length of Study:&#xD;
&#xD;
      If you are in Group A or C, you will continue to take the study drug for as long as the study&#xD;
      doctor thinks it is in your best interest. If you are in Group B, you will take the study&#xD;
      drug for 56 days and will no longer take it after surgery. You will no longer be able to take&#xD;
      the study drug if the disease gets worse, if intolerable side effects occur, or if you are&#xD;
      unable to follow study directions.&#xD;
&#xD;
      Your participation on the study will be over when you have completed the follow-up visits.&#xD;
&#xD;
      End-of-Study Visit/Call:&#xD;
&#xD;
      After you stop taking the study drug, you will have an end-of-study visit or phone call. You&#xD;
      will be asked about any other drugs you may be taking and about any side effects you may have&#xD;
      had. If you are called, the call will last about 5-10 minutes.&#xD;
&#xD;
      This is an investigational study. Vemurafenib is FDA approved and commercially available for&#xD;
      the treatment of late-stage melanoma. It is investigational to use this drug to treat thyroid&#xD;
      cancer.&#xD;
&#xD;
      Up to 22 patients will take part in this study. All will be enrolled at MD Anderson.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 7, 2012</start_date>
  <completion_date type="Anticipated">September 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent Change in ERK (Extracellular-Signal-Regulated Kinase) Phosphorylation and Tumor Size</measure>
    <time_frame>56 days</time_frame>
    <description>ERK phosphorylation and tumor size measured at baseline before first dose of Vemurafenib and again after 56 days of Vemurafenib. We will test whether correlation between percent change in ERK phosphorylation and percent change in tumor size is different from 0 with a t-test.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate</measure>
    <time_frame>56 days</time_frame>
    <description>Objective response rate defined as proportion of patients who have had a partial response (PR) or complete response (CR) after initiation of therapy with Vemurafenib, using RECIST 1.1. All patients who complete baseline and day 56 scans evaluable for this endpoint.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Thyroid Cancer</condition>
  <arm_group>
    <arm_group_label>Vemurafenib - (Presurgery)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All Groups: Vemurafenib 960 mg by mouth 2 times a day for 56 days prior to surgery (patients not planned for surgical resection will have a core biopsy at day 56 +/- 7 days).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vemurafenib (Post Surgery) - Group A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vemurafenib 960 mg by mouth two times a day 2 weeks post-surgery, or if patients have not sufficiently recovered at that point, as soon as their condition permits. Patients in Group A restaged 8 weeks after resuming drug. If patients in Group A demonstrate either stable or regressing disease, they will continue on vemurafenib with restaging occurring every 8 weeks until no longer benefitting from the drug.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Post Surgery - Group B</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Post Surgery - Group B: Patients discontinue vemurafenib after surgery but will be restaged with CT neck 8 weeks after surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vemurafenib - Group C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients not scheduled for surgical resection undergo a CT scan and core biopsy at day 56, Vemurafenib 960 mg by mouth twice a day unless there is evidence of progressive disease on day 56 CT scan. Patients evaluated for resectability after each CT scan is performed. If scheduled for resection, patient continues vemurafenib until surgery and follows same treatment schema as patients in Groups A and B.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vemurafenib (All Groups)</intervention_name>
    <description>960 mg by mouth 2 times a day 56 days prior to surgery (patients not planned for surgical resection will have a core biopsy at day 56.</description>
    <arm_group_label>Vemurafenib - (Presurgery)</arm_group_label>
    <other_name>PLX4032</other_name>
    <other_name>RO5185426</other_name>
    <other_name>Zelboraf™</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vemurafenib (Post Surgery) - Group A + C</intervention_name>
    <description>Group A: 960 mg by mouth twice a day 2 weeks post-surgery. Restaged 8 weeks after resuming drug. If patients demonstrate either stable or regressing disease, they will continue on vemurafenib with restaging occurring every 8 weeks until they are no longer benefitting from the drug.&#xD;
Group C: Patients not scheduled for surgical resection undergo a CT scan and core biopsy at day 56. Vemurafenib 960 mg by mouth twice a day, continued unless there is evidence of progressive disease on day 56 CT scan. Patients restaged every 8 weeks and continue vemurafenib until no longer benefitting from the drug. Patients evaluated for resectability after each CT scan is performed. If patient is scheduled for resection, then patient will continue vemurafenib until surgery and will follow the same treatment schema as patients in Groups A and B.</description>
    <arm_group_label>Vemurafenib (Post Surgery) - Group A</arm_group_label>
    <arm_group_label>Vemurafenib - (Presurgery)</arm_group_label>
    <arm_group_label>Vemurafenib - Group C</arm_group_label>
    <other_name>PLX4032</other_name>
    <other_name>RO5185426</other_name>
    <other_name>Zelboraf™</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Post Surgery - Group B</intervention_name>
    <description>Patients who have had a complete surgical resection, and who do not have evidence of metastatic disease will discontinue vemurafenib after surgery. Patients restaged with CT neck 8 weeks after surgery.</description>
    <arm_group_label>Vemurafenib - (Presurgery)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Primary papillary thyroid cancer (PTC), which appears to be stage T3 or T4 on imaging&#xD;
             or with macroscopic lymph node involvement AND requires surgical resection.&#xD;
&#xD;
          2. Persistent or locally recurrent PTC with macroscopic lymph node involvement which&#xD;
             requires surgical resection.&#xD;
&#xD;
          3. Patients deemed inoperable (no scheduled surgery) are eligible for this trial, as they&#xD;
             could be surgical candidates after treatment with vemurafenib. Inoperable patients&#xD;
             must be naïve to therapies targeting the MAPK pathway.&#xD;
&#xD;
          4. BRAF V600E mutation detected in the primary tumor or the recurrent/persistent tumor.&#xD;
&#xD;
          5. Total bilirubin &lt;/= 1.5 x upper limit of normal (ULN). Patients with Gilbert's&#xD;
             syndrome are excluded from this requirement. Aspartate transaminase (serum glutamic&#xD;
             oxaloacetic transaminase) / alanine transaminase (serum glutamic pyruvic transaminase)&#xD;
             (AST[SGOT]/ALT[SGPT]) &lt;/= 2.5 x ULN, (5 x ULN for patients with concurrent liver&#xD;
             metastases). Serum creatinine &lt;/= within 1.5 x ULN. Absolute neutrophil count (ANC)&#xD;
             &gt;/= 1.0 x 10^9/L; platelets &gt;/= 100 x 10^9/L, HgB&gt;9 mg/dL&#xD;
&#xD;
          6. Antiangiogenic therapy, specifically vascular endothelial growth factor (VEGF) and&#xD;
             VEGF receptor (VEGFR) inhibitors, can interfere with wound healing and therefore will&#xD;
             only be allowed if the agent has been discontinued for at least 14 days prior to day&#xD;
             1. Group C patients must be naïve to therapies which target mitogen-activated protein&#xD;
             kinase (MAPK).&#xD;
&#xD;
          7. Ability to swallow pills.&#xD;
&#xD;
          8. Eastern Cooperative Oncology Group (ECOG) performance status &lt;/= 2&#xD;
&#xD;
          9. Age &gt;/= 18&#xD;
&#xD;
         10. Ability to provide consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Histological diagnosis other than PTC. Patients with anaplastic tumors are not&#xD;
             eligible. However, patients whose tumors contain areas of un-differentiated or&#xD;
             dedifferentiated histology may enroll provided the original diagnosis was clearly PTC,&#xD;
             and the tumor histology remains predominantly papillary at enrollment.&#xD;
&#xD;
          2. Refractory nausea and vomiting, malabsorption, or significant bowel resection that&#xD;
             would preclude adequate absorption.&#xD;
&#xD;
          3. Known hepatitis B or C virus (HBV or HCV) infection, unless the patient has been&#xD;
             cleared for chemotherapy from experts on viral hepatitis (infectious disease&#xD;
             specialists or hepatologists).&#xD;
&#xD;
          4. Pregnant or lactating women. All pre-menopausal women being screened must have a&#xD;
             negative serum pregnancy test within 14 days prior to commencement of dosing. Women of&#xD;
             non-childbearing potential may be included if they are either surgically sterile or&#xD;
             have been postmenopausal for &gt;/= 1 year&#xD;
&#xD;
          5. Untreated brain metastases.&#xD;
&#xD;
          6. Chemotherapy or targeted therapy within 14 days or 5 half-lives (whichever is longer)&#xD;
             prior to the start of study treatment.&#xD;
&#xD;
          7. Patients with history of long QT syndrome, uncorrectable electrolyte abnormalities, or&#xD;
             QTc&gt;500msec.&#xD;
&#xD;
          8. History of significant cardiac disease or uncontrolled arrhythmias.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Maria E. Cabanillas, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Texas MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>University of Texas MD Anderson Cancer Center Website</description>
  </link>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>July 25, 2012</study_first_submitted>
  <study_first_submitted_qc>October 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 18, 2012</study_first_posted>
  <last_update_submitted>November 3, 2021</last_update_submitted>
  <last_update_submitted_qc>November 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 5, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Thyroid Cancer</keyword>
  <keyword>ERK</keyword>
  <keyword>Extracellular-signal-regulated kinase</keyword>
  <keyword>Biomarkers</keyword>
  <keyword>Papillary thyroid cancer</keyword>
  <keyword>PTC</keyword>
  <keyword>BRAF mutated</keyword>
  <keyword>Vemurafenib</keyword>
  <keyword>PLX4032</keyword>
  <keyword>RO5185426</keyword>
  <keyword>Zelboraf™</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thyroid Neoplasms</mesh_term>
    <mesh_term>Thyroid Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vemurafenib</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01709292
org study id: 2012-0471
secondary id: NCI-2012-02171
nct id: NCT01709292
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The goal of this clinical research study is to learn about how vemurafenib may affect certain
      biomarkers in patients with PTC. Biomarkers are in the blood/tissue and may be related to
      your reaction to the study drug. The safety of this drug will also be studied.

      Vemurafenib is designed to block the BRAF gene mutation. This mutation causes cancer and
      cancer growth. By blocking this mutation, the drug may kill the cancer cells with the
      mutation and/or stop the tumor from growing.
Study Drug Administration and Groups:

      If you are found to be eligible to take part in this study, you will take 4 tablets of
      vemurafenib by mouth 2 times each day for 56 days. You should take each dose about 12 hours
      apart. If you miss taking the drug at a scheduled time by more than 4 hours, you should skip
      that dose and wait until the next dose.

      After 56 days, the treatment you receive will depend on what group you are assigned to:

        -  If the disease has spread outside the neck, you will be in Group A.

        -  If the disease is able to be entirely removed through surgery, you will be in Group B.

        -  If the disease is unable to be operated on, you will be in Group C.

      Study Visits:

      At all visits, you will be asked about any side effects you may be having and about any other
      drugs you may be taking.

      Before you take the study drug (Baseline):

        -  You will have a procedure called a laryngoscopy, in which a tube with a small camera in
           inserted into the nose to inspect your sinus, throat, and voice box.

        -  You will have a colonoscopy if you have a history of abnormal growth in the bowel
           (polyps or colon cancer). During this procedure a tube with a small camera is inserted
           in the anus to inspect your large bowel.

      At Day 28:

        -  You will have a physical exam, including measurement of your vital signs.

        -  Your performance status will be recorded.

        -  You will have an EKG.

        -  Blood (about 1 tablespoon) will be drawn for routine tests.

      Within 1 week before Day 56, you will have CT scans of the neck, chest, and abdomen to check
      the status of the disease.

      At Day 56, if you are in Group A or B, you will have surgery to remove the tumor. You will
      sign a separate consent form that describes this surgery and its risks. If you are in Group
      C, you will have a core biopsy. During the surgery/biopsy, blood (about 1 teaspoon) will also
      be collected for biomarker testing.

      Follow-Up:

      Your follow-up after the surgery/biopsy will depend on which study group you are in.

      Groups A and C:

      If you are in Group A, you will stop taking the study drug for about 2-4 weeks after you have
      surgery. If you are in Group C, you will not stop taking the study drug. Every 4 weeks (after
      you resume taking the study drug if you are in Group A, and after the biopsy if you are in
      Group C):

        -  You will have a physical exam, including measurement of your vital signs and a skin
           exam.

        -  Your performance status will be recorded.

        -  Blood (about 1 tablespoon) will be drawn for routine tests.

        -  You will be asked about any other drugs you may be taking and about any side effects you
           may be having.

        -  If you are in Group A, these tests will also be performed the day you start taking the
           study drug again. You will also have an EKG.

      Additionally, every 8 weeks (if you are in Group A or C), you will have CT scans of the neck,
      chest, and abdomen to check the status of the disease. Blood (about 1 teaspoon) will also be
      drawn for biomarker testing at the first of these visits.

      About 1 year after your laryngoscopy and colonoscopy, these procedures will be performed
      again to check for side effects related to the study drug. If you did not receive a baseline
      colonoscopy, this procedure will be performed about 1 year after starting vemurafenib. If you
      continue on study drug for more than a year, you will have a laryngoscopy every 12 months.

      At any time the study doctor thinks it is needed, you will have a colonoscopy and
      laryngoscopy.

      About 1 year after the surgery/biopsy, you will return to clinic to check if the disease has
      come back. At this visit, you will have a CT scan or ultrasound of the neck, and blood (about
      1 tablespoon) will be drawn for tests of your thyroid function.

      If after 4 months the study doctor thinks it is in your best interest, you will only need to
      have study visits every 8 weeks. You will still have blood (about 1 tablespoon) drawn for
      routine tests at a local lab and you will be called by the study staff to check on you. Each
      call will last about 5-10 minutes.

      If you are in Group C, and if during follow-up the study doctor decides that the disease can
      be operated on, you will be crossed over to Group A or B. You will have surgery and have the
      follow-up visits described for that study group.

      Group B:

      If you are in Group B, you will have a follow-up visit about 2 weeks after surgery. The
      following tests and procedures will be performed:

        -  You will have a physical exam, including measurement of your vital signs.

        -  Your performance status will be recorded.

        -  Blood (about 1 tablespoon) will be drawn for routine tests.

        -  You will be asked about any other drugs you may be taking and about any side effects you
           may be having.

      You will have a second follow-up visit about 8 weeks after surgery. You will have a CT scan
      of the neck to check the status of the disease. You will have the option of continuing to
      receive vemurafenib if your doctor thinks it is in your best interest. If you do continue on
      vemurafenib, you will follow the Group A follow-up schedule (above).

      About 1 year after your laryngoscopy and colonoscopy, these procedures will be performed
      again to check for side effects related to the study drug. If you did not receive a baseline
      colonoscopy, this procedure will be performed about 1 year after starting vemurafenib.

      At any time the study doctor thinks it is needed, you will have a colonoscopy and
      laryngoscopy.

      About 1 year after the surgery/biopsy, you will return to clinic to check if the disease has
      come back. At this visit, you will have a CT scan or ultrasound of the neck, and blood (about
      1 tablespoon) will be drawn for tests of your thyroid function.

      Length of Study:

      If you are in Group A or C, you will continue to take the study drug for as long as the study
      doctor thinks it is in your best interest. If you are in Group B, you will take the study
      drug for 56 days and will no longer take it after surgery. You will no longer be able to take
      the study drug if the disease gets worse, if intolerable side effects occur, or if you are
      unable to follow study directions.

      Your participation on the study will be over when you have completed the follow-up visits.

      End-of-Study Visit/Call:

      After you stop taking the study drug, you will have an end-of-study visit or phone call. You
      will be asked about any other drugs you may be taking and about any side effects you may have
      had. If you are called, the call will last about 5-10 minutes.

      This is an investigational study. Vemurafenib is FDA approved and commercially available for
      the treatment of late-stage melanoma. It is investigational to use this drug to treat thyroid
      cancer.

      Up to 22 patients will take part in this study. All will be enrolled at MD Anderson.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percent Change in ERK (Extracellular-Signal-Regulated Kinase) Phosphorylation and Tumor Size
time frame: 56 days
description: ERK phosphorylation and tumor size measured at baseline before first dose of Vemurafenib and again after 56 days of Vemurafenib. We will test whether correlation between percent change in ERK phosphorylation and percent change in tumor size is different from 0 with a t-test.
measure: Objective Response Rate
time frame: 56 days
description: Objective response rate defined as proportion of patients who have had a partial response (PR) or complete response (CR) after initiation of therapy with Vemurafenib, using RECIST 1.1. All patients who complete baseline and day 56 scans evaluable for this endpoint.
arm group label: Vemurafenib - (Presurgery)
arm group type: Experimental
description: All Groups: Vemurafenib 960 mg by mouth 2 times a day for 56 days prior to surgery (patients not planned for surgical resection will have a core biopsy at day 56 +/- 7 days).
arm group label: Vemurafenib (Post Surgery) - Group A
arm group type: Experimental
description: Vemurafenib 960 mg by mouth two times a day 2 weeks post-surgery, or if patients have not sufficiently recovered at that point, as soon as their condition permits. Patients in Group A restaged 8 weeks after resuming drug. If patients in Group A demonstrate either stable or regressing disease, they will continue on vemurafenib with restaging occurring every 8 weeks until no longer benefitting from the drug.
arm group label: Post Surgery - Group B
arm group type: No Intervention
description: Post Surgery - Group B: Patients discontinue vemurafenib after surgery but will be restaged with CT neck 8 weeks after surgery.
arm group label: Vemurafenib - Group C
arm group type: Experimental
description: Patients not scheduled for surgical resection undergo a CT scan and core biopsy at day 56, Vemurafenib 960 mg by mouth twice a day unless there is evidence of progressive disease on day 56 CT scan. Patients evaluated for resectability after each CT scan is performed. If scheduled for resection, patient continues vemurafenib until surgery and follows same treatment schema as patients in Groups A and B.
intervention type: Drug
intervention name: Vemurafenib (All Groups)
description: 960 mg by mouth 2 times a day 56 days prior to surgery (patients not planned for surgical resection will have a core biopsy at day 56.
arm group label: Vemurafenib - (Presurgery)
other name: PLX4032
other name: RO5185426
other name: Zelboraf™
intervention type: Drug
intervention name: Vemurafenib (Post Surgery) - Group A + C
description: Group A: 960 mg by mouth twice a day 2 weeks post-surgery. Restaged 8 weeks after resuming drug. If patients demonstrate either stable or regressing disease, they will continue on vemurafenib with restaging occurring every 8 weeks until they are no longer benefitting from the drug.
Group C: Patients not scheduled for surgical resection undergo a CT scan and core biopsy at day 56. Vemurafenib 960 mg by mouth twice a day, continued unless there is evidence of progressive disease on day 56 CT scan. Patients restaged every 8 weeks and continue vemurafenib until no longer benefitting from the drug. Patients evaluated for resectability after each CT scan is performed. If patient is scheduled for resection, then patient will continue vemurafenib until surgery and will follow the same treatment schema as patients in Groups A and B.
arm group label: Vemurafenib (Post Surgery) - Group A
arm group label: Vemurafenib - (Presurgery)
arm group label: Vemurafenib - Group C
other name: PLX4032
other name: RO5185426
other name: Zelboraf™
intervention type: Other
intervention name: Post Surgery - Group B
description: Patients who have had a complete surgical resection, and who do not have evidence of metastatic disease will discontinue vemurafenib after surgery. Patients restaged with CT neck 8 weeks after surgery.
arm group label: Vemurafenib - (Presurgery)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Maria E. Cabanillas, MD
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: University of Texas MD Anderson Cancer Center Website
responsible party type: Sponsor
mesh term: Thyroid Neoplasms
mesh term: Thyroid Diseases
mesh term: Vemurafenib