Inclusion Criteria:

- Histologically or cytologically confirmed papillary thyroid cancer or papillary
thyroid cancer with follicular elements

- No longer amenable to radioactive iodine therapy or curative surgical resection

- Tumor is no longer iodine avid

- Tumor did not respond to the most recent radioactive iodine treatment

- Patient is ineligible for further radioactive iodine therapy due to medical
contraindications (e.g., lung toxicity)

- Measurable disease, defined as at least one lesion that can be accurately measured in
at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional
techniques or as ≥ 10 mm with spiral CT scan

- Evidence of disease progression (objective growth of existing tumors)

- New or enlarging measurable lesions within the past 12 months

- If the most recent imaging study is older than 12 months, patients will still be
eligible if objectively measurable disease progression is associated with
clinical symptoms

- Archival tumor tissue available for mutational analysis

- No known brain metastases

- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

- Life expectancy > 12 weeks

- WBC ≥ 3,000/µL

- ANC ≥ 1,500/µL

- Platelet count ≥ 100,000/µL

- Total bilirubin normal

- AST and ALT < 2.5 times upper limit of normal

- Creatinine normal OR creatinine clearance ≥ 60 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception prior to, during, and for 4 weeks
after completion of study treatment

- Able to understand and willing to sign a written informed consent document

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to AZD6244 or its excipient Captisol®

- QTc interval > 450 msec or other factors that increase the risk of QT prolongation

- Arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT
interval syndrome), including heart failure that meets NYHA class III and IV
definition

- Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory
bowel disease), or significant bowel resection that would preclude adequate
absorption

- Concurrent uncontrolled illness including, but not limited to, ongoing or active
infection or psychiatric illness/social situations that would limit compliance with
study requirements

- At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas
or mitomycin C)

- Prior treatment with tyrosine kinase inhibitors that target RET or RAF

- Prior treatment with MEK inhibitors

- Concurrent combination antiretroviral therapy for HIV-positive patients

- Concurrent medication that can prolong the QT interval

- Other concurrent investigational agents