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Ponatinib for the Treatment of Advanced and Metastatic Medullary Thyroid Cancer

Trial Status: Active

This phase II trial studies how well ponatinib works in treating patients with medullary thyroid cancer that has spread to other places in the body (advanced and metastatic). Ponatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Inclusion Criteria

  • Diagnosis of localized or metastatic unresectable MTC
  • 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 >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan
  • The last dose of previous therapy targeting 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 or vandetanib
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Leukocytes >= 3,000/uL
  • Absolute neutrophil count >= 1,500/uL
  • Platelet count >= 100,000/uL
  • Total bilirubin < 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamicoxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x institutional ULN or < 5 x ULN if liver involvement
  • Prothrombin time < 1.5 x ULN
  • Creatinine < 1.5 x ULN
  • Lipase =< 1.5 x ULN
  • Amylase =< 1.5 x 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
  • Female patients who: * Are postmenopausal for at least 1 year before the screening visit, OR * Are surgically sterile, OR * If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse
  • Male patients, even if surgically sterilized (i.e., status post-vasectomy), who: * Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or * Agree to completely abstain from heterosexual intercourse
  • Normal QT interval corrected (Fridericia, QTcF) on screening echocardiography (ECG) evaluation, defined as QTcF of =< 450 ms
  • Ability to understand and the willingness to sign a written informed consent document and follow the guidelines of the clinical protocol including visits to New York Presbyterian / Columbia University Medical Center for treatment and follow up
  • Life expectancy of greater than 12 weeks
  • Available archival tissue or willingness to undergo fresh biopsy if no archival tissue is available

Exclusion Criteria

  • Patients who are receiving any other investigational agent
  • Patients with brain metastases or spinal cord compression unless they completed radiation therapy >= 4 weeks prior to the first dose of ponatinib and are stable without steroids or anti-convulsant therapy for >= 10 days
  • Patients who cannot discontinue 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 (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 (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 non-melanoma skin cancer or cervical cancer in situ. Prior prostate cancer is also permitted if prostate specific antigen [PSA] is now undetectable.)
  • Pregnant or lactating
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to investigational agent

New York

New York
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: ACTIVE
Contact: Antonio Tito Fojo
Phone: 212-305-5098


I. Determine the objective overall response rate (complete response [CR] + partial response [PR] by Response Evaluation Criteria in Solid Tumors [RECIST]) to ponatinib in patients with advanced or metastatic medullary thyroid carcinoma (MTC) previously treated with cabozantinib or vandetanib.


I. To determine the safety and tolerability of ponatinib in patients with MTC.

II. To determine if changes in serum levels of MTC tumor markers calcitonin (CTN) and carcinoembryonic antigen (CEA) correlate with clinical response and prognosis.

III. To determine progression free survival (PFS)

IV. To determine overall survival (OS).

V. To later determine, in an exploratory manner, if RET mutations can be detected from circulating tumor DNA collected from the serum of study patients.


Patients receive ponatinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center

Principal Investigator
Antonio Tito Fojo

  • Primary ID AAAR5196
  • Secondary IDs NCI-2019-05461
  • ID NCT03838692