Ponatinib in the Treatment of FGFR Mutation Positive Recurrent or Persistent Endometrial Carcinoma

Exclusion Criteria

• •Patients must not have had prior therapy with ponatinib or anti-FGFR (fibroblast growth factor receptor) therapy including brivanib, BIBF1120, and E7080.
• •Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, localized cancer of the breast, and localized cancer of the head and neck, are excluded if there is any evidence of the other malignancy being present within the last five years. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.
• •Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of endometrial cancer within the last five years are excluded. Prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease.
• •Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of endometrial cancer within the last five years are excluded. Patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease.
• •Patients must not be on required chronic anti-platelet therapy (aspirin \>300 mg/day, or clopidogrel greater than or equal to 75mg/day).
• •Patients must not have any gastrointestinal bleeding or any other hemorrhage/bleeding event ≥ grade 3 within 30 days prior to study entry.
• •Patients must not have a history of poor wound healing, non-healing ulcers or bone fractures within the last 3 months.
• •Patients must not have uncontrolled or significant cardiovascular disease including:
• •* Myocardial infarction within 3 months
• •* Uncontrolled angina within 3 months
• •* Class III-IV New York Heart Association (NYHA) congestive heart failure (see Appendix B)
• •* Uncontrolled hypertension (systolic BP \> 150 or diastolic BP \> 100 mmHg for 24 hours) despite optimized anti-hypertensive therapy. BP must be below 150/100 mmHg at screening. Subjects with a history of hypertension who are receiving treatment with calcium channel blockers that are CYP3A4 inhibitors should be changed to an alternative antihypertensive medication before study entry
• •* History of stroke, TIA, or other CNS ischemic event
• •* Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
• •* Pre-therapy Left Ventricle Ejection Fraction (LVEF) ≤ 50%
• •* Valvular heart disease ≥ grade 2
• •Patients must not have a serious uncontrolled medical disorder or active infection which would impair the ability of the subject to receive protocol therapy or whose control may be jeopardized by the complications of this therapy.
• •Patients must not have any pre-existing thyroid abnormality with thyroid function that cannot be maintained in the institutional normal range with medication.
• •Patients must not have hyponatremia (sodium \< 130mEq/L).
• •Patients must not have active/known HIV, Hepatitis B, or Hepatitis C.
• •Patients must not have known brain metastases. Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurological dysfunction that would confound the evaluation of neurologic and other adverse events.
• •Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biological composition to ponatinib or other agents used in this study.
• •Patients must not be pregnant or nursing.
• •Patients must not have untreated malabsorption syndrome.
• •Patients must not have baseline serum potassium \< 3.5 mmol/L (potassium supplementation may be given to restore the serum potassium above this level prior to study entry).
• •Patients on therapeutic warfarin anticoagulation will be excluded. Patients converted to anticoagulation with a heparin compound will be allowed provided the PT INR is ≤ 1.5.
• •Patients with:
• •1. History of acute pancreatitis within 1 year of study or history of chronic pancreatitis
• •2. History of alcohol abuse
• •3. History of uncontrolled hypertriglyceridemia (triglycerides \> 450 mg/dL)
• •Women and Minorities
• •Participating institutions will not exclude potential subjects from participating in this or any study solely on the basis of ethnic origin or socioeconomic status. Every attempt will be made to enter all eligible patients into this protocol and therefore address the study objectives in a patient population representative of the entire endometrial cancer population treated by participating institutions.