Ponatinib for Advanced Medullary Thyroid Cancer

* INCLUSION CRITERIA:
* Diagnosis of localized or metastatic unresectable medullary thyroid cancer (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 computed tomography (CT) scan.
* Disease amenable to biopsy and agree to undergo biopsy for molecular analysis
* The last dose of previous therapy targeting rearranged during transfection (RET) kinase must be given at least 4 weeks prior to the first dose of ponatinib.
* Previous treatment with cytotoxic chemotherapy, immunotherapy, or radiotherapy are permitted, if the last dose was given at least 4 weeks prior to the first dose of ponatinib
* Patient must have failed (progressed on or been intolerant of) prior treatment with cabozantinib and vandetanib.
* Age greater than or equal to 18 years old
* Eastern Cooperative Oncology Group (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 100,000 microL
  * Total bilirubin \< 1.5 times upper limit of normal (ULN)
  * Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase(SGOT)/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (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 electrocardiogram (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 National Cancer Institute (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:

  * History of myocardial infarction
  * History of atrial or ventricular arrhythmia
  * Unstable angina within 6 months prior to first dose of ponatinib
  * History of congestive heart failure
  * Left ventricular ejection fraction fraction (LVEF) less than lower limit of normal
  * History of peripheral arterial occlusive disease
  * History of cerebrovascular accident or transient ischemic attack
  * Venous thromboembolism including deep venous thrombosis or pulmonary embolism within 6 months prior to enrollment
* 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 virus\[HCV\]. 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 prostatic specific antigen (PSA) is now undetectable.)
* Pregnant or lactating