|Inclusion Criteria:||1) Male or female patients >/= 18 years of age|
2) Histologically confirmed papillary thyroid cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. NOTE: Patients whose tumors exhibit areas of "other histology" may be enrolled, provided the tumor histology remains predominantly papillary. Patients whose tumors exhibit "mixed" histology may be discussed with the Medical Monitor if there are questions about eligibility.
3) BRAF V600-positive thyroid cancer tissue, as determined by the Roche-designated Central Reference Laboratory using the cobas« 4800 BRAF V600 Mutation Test. Testing requires a formalin-fixed paraffin-embedded tumor tissue block or unstained sections from such a block. Samples may be either archival or new. Fine needle and core needle biopsies will not be accepted.
4) Must have radioactive iodine (RAI) resistant disease, defined by any one of the following: (1) lack of RAI uptake on either a low-dose diagnostic or a post-therapy RAI scan in the measurable lesion (or lesions) demonstrated previously (without time limitation), or (2) radiographic progression of disease within 18 months of last course of RAI therapy despite the presence of RAI uptake on the scans performed with that prior therapy, or (3) patient that has exceeded a cumulative activity of at least 600 mCi of radioiodine therapy
5) Thyroid carcinoma tissue, either archival or recent biopsy, must be available for submission and review by a central pathology laboratory.
6) Allowed Prior therapy: Cohort 1 may have received surgery, RAI, and/or standard of care conventional chemotherapy (e.g., doxorubicin). Cohort 2: may have received surgery, RAI and standard of care chemotherapy (e.g., doxorubicin), and must also have received prior treatment with investigational or commercial tyrosine kinase inhibitor with activity against VEGFR2 provided the drug is not a specific/selective BRAF or MEK pathway inhibitor. [Note: Acceptable prior chemotherapy can be discussed with the sponsor].
7) Must have fully recovered from the effects of any previous therapies.
8) Radiologic (computed tomography [CT] or magnetic resonance imaging [MRI]) evidence of clinically relevant disease progression (as per RECIST 1.1) within the preceding 14 months prior to planned first treatment.
9) Measurable disease (by RECIST Version 1.1 criteria)
10) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
11) Life expectancy > 3 months
12) Ability to swallow pills
13) Must have a head CT/MRI to evaluate for central nervous system (CNS) metastasis within 28 days prior to study drug treatment (Cycle 1 Day 1). Patients with radiographically stable, asymptomatic previously treated lesions are eligible provided: (1) Patient has received prior treatment [including radiation therapy, stereotactic radiosurgery, surgical resection] to the site(s) of CNS metastatic disease >/= 28 days prior to starting study treatment, (2) Patient has no requirement for glucocorticoids, and discontinued >/= 21 days prior to starting study treatment), (3) Patient is not taking anticonvulsants (discontinuedat least 3 weeks prior to treatment), and (4) Patient has no overt evidence of neurological deficit
14) Prior Surgery (excluding tumor biopsy at baseline for biomarker analysis) must have occurred at least 14 days prior to first dose of study treatment, and patients must have recovered from any effects from surgery and have adequate wound healing prior to first dose of study treatment.
15) External beam radiotherapy for the treatment of a symptomatic (e.g. bone) metastasis as clinically indicated must be at least 14 days prior to first dose of study treatment
16) Thyroid stimulating hormone (TSH) level <0.5 mIU/L
17) Completed baseline skin exam by a dermatologist or other qualified physician for cutaneous squamous cell carcinoma. Exam must be negative or if, suspected cutaneous squamous-cell carcinoma (SCC), basal-cell carcinoma (BCC), or other suspicious lesions are identified they must be excised, and there must be adequate wound healing prior to study treatment.
18) Adequate hematologic, renal and liver function: (1) Absolute neutrophil count (ANC) >1.5 x 10^9/L, (2) Platelet count >100 x 10^9/L, (3) Hemoglobin >9 g/dL , (4) Serum creatinine </= 1.5 X ULN or CrCl>40 ml/hr by Cockcroft-Gault formula , (5) AST and ALT </= 2.5 times upper limit of normal (ULN) (</= 5 times ULN for patients with concurrent liver metastases) , (6) Bilirubin </= 1.5 times ULN, (7) Alkaline phosphatase </= 2.5 times ULN (</= 5 times ULN for patients with concurrent liver metastases)
19) Negative serum pregnancy test within 14 days prior to commencement of dosing in pre-menopausal women. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for >/= 1 year
20) Fertile men and women must use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician (in accordance with local requirements)
21) Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before trial entry
22) Before study entry, signed informed consent must be obtained from patient prior to performing any studyrelated procedures