POETIG Trial - POnatinib After rEsisTance to Imatinib in GIST

Exclusion Criteria

• •1. Patients lacking primary mutations of KIT or PDGFRA (including Succinate-Dehydrogenase(SDH)-deficient GIST)
• •2. Major surgery within 28 days prior to initiating therapy
• •3. History of bleeding disorder
• •4. History of acute pancreatitis within 1 year of study or history of chronic pancreatitis
• •5. History of alcohol and /or drug abuse
• •6. Uncontrolled hypertriglyceridemia (triglycerides \>450 mg/dL)
• •7. Clinically significant, uncontrolled, or active cardiovascular disease, or other arterial or venous vascular occlusion diseases specifically including, but not restricted to: Myocardial infarction within 6 months prior to enrollment Unstable angina within 6 months prior to enrollment Congestive heart failure within 6 months prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards History of clinically significant (as determined by the treating physician) atrial arrhythmia Any history of ventricular arrhythmia Cerebrovascular accident or transient ischemic attack within 6 months prior to enrollment Any history of peripheral arterial occlusive disease requiring revascularization Venous thromboembolism including deep venous thrombosis or pulmonary embolism within 6 months prior to enrollment
• •8. Uncontrolled hypertension (diastolic blood pressure \>90 mm Hg; systolic \>140 mm Hg). Patients with hypertension should be under treatment on study entry to effect blood pressure control
• •9. Taking medications that are known to be associated with Torsades de Pointes (Appendix A)
• •10. Taking any medications or herbal supplements that are known to be strong inhibitors of CYP3A4 within at least 14 days before the first dose of ponatinib (Appendix B)
• •11. Ongoing or active infection. This includes but is not limited to the requirement for intravenous antibiotics
• •12. Known history of human immunodeficiency virus. Testing is not required in the absence of prior documentation or known history
• •13. Pregnant or breastfeeding
• •14. Malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of the study drug
• •15. Individuals with a history of a different malignancy, other than cervical cancer in situ, basal cell or squamous cell carcinoma of the skin, are ineligible, except if they have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy OR if the other primary malignancy is neither currently clinically significant nor requiring active intervention.
• •16. Use of any approved TKIs or investigational agents within 2 weeks or 6 half-lives of the agent, whichever is longer, prior to receiving study drug
• •17. Any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of the drug
• •18. History of apoplectic insult