Inclusion Criteria

- INCLUSION CRITERIA:

- Diagnosis of localized or metastatic unresectable MTC. The histological diagnosis of
MTC must be confirmed on review of submitted tumor tissue by the Laboratory of
Pathology in the National Cancer Institute

- Measurable disease, defined as at least one lesion that can be accurately measured in
at least one dimension (longest diameter to be recorded for non-nodal lesions and
short axis for nodal lesions) as greater than or equal to 20 mm with conventional
techniques or as greater than or equal to 10 mm with spiral CT scan.

- Disease amenable to biopsy and agree to undergo biopsy for molecular analysis

- Previous therapy targeting RET kinase is permitted if the last dose was given at
least 4 weeks prior to the first dose of ponatinib

- Previous cytotoxic chemotherapy, immunotherapy, or radiotherapy are permitted, if the
last dose was given at least 4 weeks prior to the first dose of ponatinib

- Age greater than or equal to 18 years old

- ECOG performance status less than or equal to 2

- Normal organ and marrow function as defined below:

- Leukocytes greater than or equal to microL

- Absolute neutrophil count 1,500/microL

- Platelet count greater than or equal to microL

- Total bilirubin < 1.5 times ULN

- AST(SGOT)/ALT(SGPT) < 2.5 times institutional ULN or < 5 times ULN if liver
involvement

- Prothrombin Time < 1.5 times ULN

- Creatinine < 1.5 times ULN

- Lipase less than or equal to 1.5 times ULN

- Negative pregnancy test for women of childbearing potential. The effects of ponatinib
on the developing human fetus are unknown. For this reason, women of childbearing
potential and men must agree to use adequate contraception (hormonal or barrier
method of birth control; abstinence) prior to study entry and for the duration of
study participation. Should a woman become pregnant or suspect she is pregnant while
she or her partner is participating in this study, she should inform her treating
physician immediately.

- Normal QT interval corrected (Fridericia) (QTcF) on screening ECG evaluation, defined
as QTcF of less than or equal to 450 ms in males or less than or equal to 470 ms in
females.

- Ability to understand and the willingness to sign a written informed consent document
and follow the guidelines of the clinical protocol including visits to NCI, Bethesda,
Maryland for treatment and follow up visits.

EXCLUSION CRITERIA:

- Patients who are receiving any other investigational agent.

- Patients with brain metastases or spinal cord compression unless they completed
radiation therapy greater than or equal to 4 weeks prior to the first dose of
ponatinib and are stable without steroids or anti-convulsant therapy for greater than
or equal to 10 days.

- Medications that are known to be associated with Torsades de Pointes.

- Uncontrolled hypertension (systolic blood pressure > 150 or diastolic blood pressure
> 100

- Significant or active cardiovascular disease, specifically including but not
restricted to:

- Myocardial infarction within 3 months prior to first dose of ponatinib

- History of clinically significant atrial arrhythmia or ventricular arrhythmia

- Unstable angina within 3 months prior to first dose of ponatinib

- Congestive heart failure within 3 months prior to first dose of ponatinib

- A history of pancreatitis or alcohol abuse

- Uncontrolled hypertriglyceridemia (> 450 mg/dL)

- Major surgery (with the exception of minor surgical procedures, such as catheter
placement or tumor biopsy) within 28 days prior to the first dose of ponatinib

- Ongoing or active infection including known history of human immunodeficiency virus
[HIV], hepatitis B virus [HBV], or hepatitis C [HCV]. Testing for these viruses is
not required in the absence of a history of infection.

- Suffer from any condition or illness that, in the opinion of the investigator, would
compromise patient safety or interfere with the evaluation of the safety of the study
drug

- Evidence of a bleeding diathesis that cannot be corrected with standard therapy or
factor replacement

- Presence of another primary malignancy within the past 2 years (except for
nonmelanoma skin cancer or cervical cancer in situ. Prior prostate cancer is also
permitted if PSA is now undetectable.)

- Pregnant or lactating