Re-differentiation of Radioiodine-Refractory BRAF V600E-mutant Papillary Thyroid Carcinoma With GSK2118436

You will take GSK2118436 capsules by mouth for 28 straight days. If your Day 28 whole body
radioactive iodine scan demonstrates significant uptake of iodine, you will take GSK2118436
for an additional 14 days (Days 29-42). You will be given a drug diary to record when you
take GSK2118436. This diary will also contain instructions on how to take GSK2118436.

Prior to Day 1

- Optional fine needle aspirate (pre-treatment) Day 1

- Vital signs

- Routine blood tests (2 tablespoons)

- Research blood sample for Circulating Tumor Cells (CTCs). (4 teaspoons of blood)

- Optional research blood sample for CTCs 4-6 hours after the first dose of GSK2118436

Day 2:

- Optional research blood sample for CTCs 4-6 hours after the first dose of GSK2118436
Day 3-5: Research blood sample for CTCs Days 8 and 15

- Vital signs

- Routine blood tests (2 tablespoons)

- Research blood sample for CTCs. (4 teaspoons of blood)

- Optional fine needle aspirate (Day 15 only) Low Iodine Diet: You will begin a low
iodine diet on Day 15, in preparation for Day 23 when you will receive radioactive
iodine (131I). The study team will provide you with instructions on this diet. The low
iodine diet will be continued until the whole body scan is complete. For those
participants who will receive a therapeutic dose of radioactive iodine on Day 37, the
low iodine diet will be continued until the Day 42 whole body scan is complete.

Days 21 and 22: The drug thyrogen will be administered as in injection into your buttocks on
Days 21 and 22 in preparation for your whole body radioactive iodine scan on Day 28.
Thyrogen is used as a diagnostic tool to help determine the status of your cancer and is
approved for use in thyroid cancer patients.

Day 23: To prepare for the whole body radioactive iodine scan, you will be asked to swallow
a capsule of radioactive iodine which will be absorbed by any remaining thyroid cells in
your body. Radioactive iodine is approved for use in thyroid cancer patients. You will then
be asked to return for the scan on Day 28.You will be asked to sign a separate consent for
the radioactive iodine.

Days 1-28:

- Optional repeat fine needle aspirate Day 28

- Whole body radioactive iodine scan to assess your thyroid cancer

If your Day 28 whole body radioactive iodine scan demonstrates significant uptake of iodine,
you will have the following tests done within 24 hours:

- Vital signs

- Routine blood tests (2 tablespoons)

- Research blood sample for CTCs. (4 teaspoons of blood)

- An injection of a therapeutic dose of radioactive iodine will be administered. If your
Day 28 whole body radioactive iodine scan does not demonstrate significant uptake of
iodine, you will be removed from the research study. You will have a 3 month follow up
appointment as outlined below.

If your Day 28 whole body radioactive iodine scan demonstrates significant uptake of iodine,
you will continue treatment with GSK2118436 and have the following study visits:

Days 35 and 36: The drug thyrogen will be administered as in injection into your buttocks on
Days 35 and 36 in preparation for your whole body radioactive iodine scan on Day 42.

Day 37: You will be given a therapeutic dose of radioactive iodine. You will be given a
separate consent form to sign for your radioactive iodine treatment. You will then be asked
to return for the whole body radioactive iodine scan on Day 42.

Day 39:

- Vital signs

- Routine blood tests (1 tablespoon)

Day 42:

- Whole body radioactive iodine scan

- Research blood sample for CTCs. (4 teaspoons of blood)

After the final dose of the study drug: All participants will have a follow up visit 3
months after you stop the study drug. You will have the following tests at this visit:

- Routine blood tests (2 tablespoons)

- Research blood sample for CTCs. (4 teaspoons of blood)

- An assessment of your tumor by CT scan or PET/CT scan of your neck, chest, abdomen and
pelvis.

- Those participants who had a therapeutic dose of radioactive iodine on Day 37 will have
a whole body radioactive iodine scan.

- Optional fine needle aspirate

Inclusion Criteria:

- Histologically confirmed papillary thyroid carcinoma, including its variants, such as
tall cell PTC or poorly differentiated thyroid carcinoma, that is metastatic or
unresectable AND harbors a BRAF V600E mutation

- Evaluable disease, as defined by at least one lesion that can be accurately measured
in at least one dimension on CT scan or ultrasound, if present in the neck

- Radioiodine-refractory disease

- Life expectancy > 6 months

- Able to swallow and retain oral medication

- Normal organ and marrow function

Exclusion Criteria:

- Pregnant or breastfeeding

- Previous treatment with a specific BRAF or MEK inhibitor

- Receiving any other study agents

- Known brain metastases

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to GSK2118436, bovine TSH, mannitol or iodine

- Active gastrointestinal disease or other condition that will interfere significantly
with the absorption of drugs

- History of known glucose-6-phosphate dehyrogenase (G6PD) deficiency

- Corrected QT interval >/= 480 msecs; history of acute coronary syndromes (including
unstable angina), coronary angioplasty, or stenting within the past 24 weeks; Class
II, III, or IV heart failure, abnormal cardiac valve morphology; or history of known
cardiac arrhythmias

- Taking herbal remedies

- Subjects with significant symptoms from their thyroid cancer, or have a large burden
of rapidly progressive iodine-refractory PTC who are in need of other systemic
therapy, as judged by their treating physician

- Uncontrolled current illness including, but not limited to: ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, uncontrolled hypertension or psychiatric illness/social situations that
would limit compliance with study requirements

- History of a different malignancy unless disease-free for at least 5 years and deemed
to be at low risk for recurrence

- HIV-positive on combination antiretroviral therapy