Inclusion Criteria:

- Patients must have recurrent or persistent endometrial carcinoma which is refractory
to curative therapy or established treatments. Histologic confirmation of the
original primary tumor is required. Patients with the following histologic epithelial
cell types are eligible: endometrioid adenocarcinoma.

- All patients must have measurable disease. Measurable disease is defined as at least
one lesion that can be accurately measured in at least one dimension (longest
dimension to be recorded). Each lesion must be ≥ 20 mm when measured by conventional
techniques, including palpation, plain x-ray, CT, and MRI, or ≥ 10 mm when measured
by spiral CT.

Patients must have at least one "target lesion" to be used to assess response on this
protocol as defined by RECIST 1.1 (Section 11.1). Tumors within a previously irradiated
field will be designated as "non-target" lesions unless progression is documented or a
biopsy is obtained to confirm persistence at least 90 days following completion of
radiation therapy.

- Patients must have a documented FGFR2 activating mutation either on primary,
recurrent or metastatic biopsy. Over 90% of FGFR2 mutations occur at 7 codons.
Activating mutations are defined as the known FGFR2 hotspots at S252W, P253R, S373C,
Y376C, C383R, N550K, N550H, K660E.

- Patients who have received one or two prior regimen must have a GOG Performance
Status of 0, 1, or 2. Patients who have received three prior regimens must have a GOG
Performance Status of 0 or 1.

- Patients must be ≥ 18 years of age.

- Patients must be able to swallow tablets.

- Patients must have recovered from the effects of recent surgery, radiotherapy, or
chemotherapy.

- Patients should be free of active infection requiring antibiotics (with the exception
of uncomplicated UTI).

- Any hormonal therapy directed at the malignant tumor must be discontinued at least
one week prior to registration.

- Any other prior therapy directed at the malignant tumor, including immunologic
agents, must be discontinued at least three weeks prior to registration.

- Patients must have had at least one prior chemotherapeutic regimen for management of
endometrial carcinoma. Chemotherapy administered in conjunction with primary
radiation as a radio-sensitizer will be counted as a systemic chemotherapy regimen.
Patients may have received prior anti-angiogenic compounds (i.e., bevacizumab).

Patients are allowed to receive, but are not required to receive, up to two additional
cytotoxic regimens for management of recurrent or persistent endometrial disease according
to the following definition:

Cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of
dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or
gastrointestinal mucosa.

- Patients must have adequate bone marrow function defined as:

- Absolute neutrophil count (ANC) ≥ 1,500/mcl

- Platelets ≥ 100,000/mcl

- Hemoglobin > 9 g/dl

- Patients must have adequate renal function defined as:

• Creatinine ≤ 1.5 x institutional upper limit normal (ULN)

- Proteinuria must be ≤ 3+ by dipstick at baseline. If the urine dipstick is > 3+, a
24-hour protein level must be performed. The 24-hour protein level must be ≤ 3.5
g/24 hours.

- Patients must have adequate hepatic function defined as:

- Bilirubin ≤ 1.5 x ULN

- AST (SGOT), ALT (SGPT), and alkaline phosphatase ≤ 2.5 x ULN

- Albumin ≥ 2.5 g/dl

- Patients must have adequate neurologic function defined as:

• Neuropathy (sensory and motor) ≤ grade 1

- Patients must have adequate blood coagulation parameters defined as:

- PT such that international normalized ratio (INR) is ≤ 1.5

Patients on therapeutic warfarin are excluded from trial; anticoagulation with a heparin
or heparin-like compound is permitted provided patient's PT INR is ≤ 1.5.

- Patients must be able to understand and willing to sign an approved informed consent
and authorization permitting release of personal health information.

- Patients of childbearing potential must have a negative serum pregnancy test
performed 48 hours prior to first dose and be practicing an effective form of
contraception during the study and for at least 3 months after receiving the final
treatment of ponatinib. Effective contraception is defined as hormonal or barrier
method, or abstinence.

- Patients must have a baseline electrocardiogram completed prior to study entry with
QTc ≤ 450 msec. Baseline ECG should be repeated if QTc is found to be > 450 msec.
QTc must NOT be > 450 msec on both ECGs performed during the same visit.

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.