Ponatinib for Advanced Medullary Thyroid Cancer

Stopped early · Phase 2

Conditions studied: Thyroid Neoplasms

In brief

Background: * Medullary thyroid cancer (MTC) represents 5% of thyroid cancers and presents as a hereditary (25% of cases) or sporadic (75% of cases) neuroendocrine malignancy. * MTC arises from the parafollicular C-cells of the thyroid. * Germline mutations in the rearranged during transfection (RET) proto-oncogene occur in virtually all of hereditary MTC cases, and somatic RET mutations occur in 50% of sporadic cases. * Drugs targeting RET kinase such as vandetanib and cabozantinib have shown efficacy in the treatment of advanced or metastatic MTC, however, more effective RET inhibitors are needed for previously untreated patients as well as patients who have become refractory to other molecular targeted therapeutics (MTTs). * Ponatinib, a drug that is Food and Drug Administration (FDA) approved as a therapy for chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), is a potent inhibitor of RET kinase. Primary Objective: -To determine the objective overall response rate (complete response \[CR\] + partial response \[PR\] by Response Evaluation Criteria in Solid Tumors (RECIST) to ponatinib in the treatment of patients with advanced or metastatic MTC previously treated with cabozantinib and vandetanib who: 1) have tumors with RET mutations and 2) have tumors without RET mutations. Eligibility: * Patients must have histologically confirmed, unresectable, locally advanced or metastatic MTC, with measurable disease by RECIST criteria. * Patients must have disease amenable to biopsy and be willing to undergo biopsy for molecular analysis, and also have adequate archival material from their thyroidectomy or from a tumor biopsy obtained prior to beginning any systemic therapy. * Patients must have failed or been intolerant to prior treatment with both cabozantinib and vandetanib. * The last dose of prior systemic therapy must be more than 28 days prior to the first dose of ponatinib * Radiation therapy is permitted if the last treatment was received more than 28 days prior to the first dose of ponatinib. Design: * Open label phase II trial with 2 treatment groups: * RET mutation positive MTC, previously treated with vandetanib and cabozantinib * RET mutation negative MTC, previously treated with vandetanib and cabozantinib * Patients will receive ponatinib 30 mg orally daily until disease progression or until the development of intolerable side effects. * Tumor response will be assessed by RECIST 1.1 criteria at 8 weeks and then every 12 weeks thereafter. After one year on study, tumor response will be assessed every 16 weeks. * Patients will have a biopsy of their MTC for molecular analysis prior to initiating treatment with ponatinib. Patients will also have a biopsy of their MTC at the time of tumor progression, should that occur.

Key facts

Study ID: NCT01838642
Run by: National Institutes of Health Clinical Center (CC)
People needed: 3
Starts: 2013-03-01
Expected to finish: 2016-01-01
Last updated by the study team: 2017-02-15

Who can join

Age: 18 and older, up to 99. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

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

Where it is running

National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.