Vemurafenib Neoadjuvant Trial in Locally Advanced Thyroid Cancer

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 naïve 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 naïve 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.