Clinical Trials /

Vemurafenib Neoadjuvant Trial in Locally Advanced Thyroid Cancer

NCT01709292

Description:

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.

Related Conditions:
  • Thyroid Gland Papillary Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Vemurafenib Neoadjuvant Trial in Locally Advanced <span class="go-doc-concept go-doc-disease">Thyroid Cancer</span>

Title

  • Brief Title: Vemurafenib Neoadjuvant Trial in Locally Advanced Thyroid Cancer
  • Official Title: Pharmacodynamic Study of Vemurafenib in the Neoadjuvant Setting in Patients With Locally Advanced Thyroid Cancer
  • Clinical Trial IDs

    NCT ID: NCT01709292

    ORG ID: 2012-0471

    NCI ID: NCI-2012-02171

    Trial Conditions

    Thyroid Cancer

    Trial Interventions

    Drug Synonyms Arms
    Vemurafenib (All Groups) PLX4032, RO5185426, Zelboraf Vemurafenib - Presurgery
    Vemurafenib (Post Surgery) - Group A + C PLX4032, RO5185426, Zelboraf Vemurafenib - Presurgery, Vemurafenib (Post Surgery) - Group A, Vemurafenib (Post Surgery) - Group C

    Trial Purpose

    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.

    Detailed Description

    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.

    Trial Arms

    Name Type Description Interventions
    Vemurafenib - Presurgery Experimental 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). Vemurafenib (All Groups), Vemurafenib (Post Surgery) - Group A + C
    Vemurafenib (Post Surgery) - Group A Experimental 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. Vemurafenib (Post Surgery) - Group A + C
    Post Surgery - Group B No Intervention Post Surgery - Group B: Patients discontinue vemurafenib after surgery but will be restaged with CT neck 8 weeks after surgery.
    Vemurafenib (Post Surgery) - Group C Experimental 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. Vemurafenib (Post Surgery) - Group A + C

    Eligibility Criteria

    Inclusion Criteria:

    1. Primary papillary thyroid cancer (PTC), which appears to be stage T3 or T4 on imaging
    or with macroscopic lymph node involvement AND requires surgical resection.

    2. Persistent or locally recurrent PTC with macroscopic lymph node involvement which
    requires surgical resection.

    3. Patients deemed inoperable (no scheduled surgery) are eligible for this trial, as
    they could be surgical candidates after treatment with vemurafenib. Inoperable
    patients must be nave to therapies targeting the MAPK pathway.

    4. BRAF V600E mutation detected in the primary tumor or the recurrent/persistent tumor.

    5. Total bilirubin </= 1.5 x upper limit of normal (ULN). Patients with Gilbert's
    syndrome are excluded from this requirement. Aspartate transaminase (serum glutamic
    oxaloacetic transaminase) / alanine transaminase (serum glutamic pyruvic
    transaminase) (AST[SGOT]/ALT[SGPT]) </= 2.5 x ULN, (5 x ULN for patients with
    concurrent liver metastases). Serum creatinine </= within 1.5 x ULN. Absolute
    neutrophil count (ANC) >/= 1.0 x 10^9/L; platelets >/= 100 x 10^9/L, HgB>9 mg/dL

    6. Antiangiogenic therapy, specifically vascular endothelial growth factor (VEGF) and
    VEGF receptor (VEGFR) inhibitors, can interfere with wound healing and therefore will
    only be allowed if the agent has been discontinued for at least 14 days prior to day
    1. Group C patients must be nave to therapies which target mitogen-activated protein
    kinase (MAPK).

    7. Ability to swallow pills.

    8. Eastern Cooperative Oncology Group (ECOG) performance status </= 2

    9. Age >/= 18

    10. Ability to provide consent.

    Exclusion Criteria:

    1. Histological diagnosis other than PTC. Patients with anaplastic tumors are not
    eligible. However, patients whose tumors contain areas of un-differentiated or
    dedifferentiated histology may enroll provided the original diagnosis was clearly
    PTC, and the tumor histology remains predominantly papillary at enrollment.

    2. Refractory nausea and vomiting, malabsorption, or significant bowel resection that
    would preclude adequate absorption.

    3. Known hepatitis B or C virus (HBV or HCV) infection, unless the patient has been
    cleared for chemotherapy from experts on viral hepatitis (infectious disease
    specialists or hepatologists).

    4. Pregnant or lactating women. All pre-menopausal women being screened must have a
    negative serum pregnancy test within 14 days prior to commencement of dosing. Women
    of non-childbearing potential may be included if they are either surgically sterile
    or have been postmenopausal for >/= 1 year

    5. Untreated brain metastases.

    6. Chemotherapy or targeted therapy within 14 days or 5 half-lives (whichever is longer)
    prior to the start of study treatment.

    7. Patients with history of long QT syndrome, uncorrectable electrolyte abnormalities,
    or QTc>500msec.

    8. History of significant cardiac disease or uncontrolled arrhythmias.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Percent Change in ERK (Extracellular-Signal-Regulated Kinase) Phosphorylation and Tumor Size

    Secondary Outcome Measures

    Objective Response Rate

    Trial Keywords

    Thyroid Cancer

    ERK

    Extracellular-signal-regulated kinase

    Biomarkers

    Papillary thyroid cancer

    PTC

    BRAF mutated

    Vemurafenib

    PLX4032

    RO5185426

    Zelboraf