Ponatinib for Patients Whose Advanced Solid Tumor Cancer Has Activating Mutations Involving the Following Genes: FGFR1, FGFR2, FGFR3, FGFR4, RET, KIT.

Inclusion Criteria

• Patients with histologically or cytologically confirmed diagnosis of refractory metastatic solid tumor or chronic hematological malignancy who are eligible for investigational drug therapy
• Patients must have tumor suitable for biopsy (as assessed by trained specialists in interventional radiology) and medically fit to undergo a biopsy or surgical procedure OR if patients do not have a tumor suitable for biopsy but have another tissue available for molecular evaluation
• Patients should have activating genomic alterations in FGFR (mutations, fusions or amplifications [> 6 copies]) or activating genomic alterations in KIT, platelet-derived growth factor receptor alpha [PDGFRα], ret proto-oncogene [RET], ABL proto-oncogene 1, non-receptor tyrosine kinase [ABL1] and fms-related tyrosine kinase 3 [FLT3] by any validated Clinical Laboratory Improvement Amendments [CLIA]-certified molecular testing (fluorescent in situ hybridization [FISH], polymerase chain reaction [PCR] or sequencing data are acceptable); CLIA validated results from other institutions; diagnostic labs (e.g. foundation medicine) are acceptable; additional types of activating alterations in these genes can be approved by the principal investigator (PI)
• Patients with advanced cancers should have had at least one prior therapy that is considered standard for that disease type
• Patients with solid tumors must have measurable disease (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1), 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, magnetic resonance imaging (MRI), or calipers by clinical exam
• Eastern Cooperative Oncology Group (ECOG) performance status = = 80%)
• Life expectancy of greater than 3 months
• Patients with multiple malignancies remain eligible
• Patients with an inherited cancer syndrome or a medical history suggestive of an inherited cancer syndrome remain eligible
• Patients must have controlled blood pressure with a systolic blood pressure = 1,500/mcL
• Platelets >= 75,000/mcL
• Total bilirubin = = institutional lower limit of normal by echocardiogram (ECHO) or multi gated acquisition (MUGA)
• Serum creatinine = = 50 mL/min OR 24-hour urine creatinine clearance >= 50 mL/min
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Patients with acute hematological malignancies
• Patients who have not received any prior treatment.
• Patients with known ponatinib-resistant gene alterations
• PDGFRA D842V mutation
• cKIT D816V mutation
• FLT3 D835V/Y/H/F or Y842C mutations
• FGFR3 K652E mutation
• Major surgery (e.g. thoracic, abdominal, vascular, neurosurgery) within 28 days prior to initiating therapy
• History of acute pancreatitis within one year of study or history of chronic pancreatitis
• History of alcohol abuse
• Have uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL)
• Patients with history of clinically significant bleeding disorder
• Pregnant women are excluded from this study because ponatinib can affect embryo-fetal development. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ponatinib breastfeeding must be discontinued.
• Patients who are incarcerated are not eligible
• Patients with any history of arterial thromboembolic disease; any patient with a history of myocardial infarction (MI), stroke, transient ischemic attack (TIA), unstable angina or peripheral vascular disease will not be eligible
• Patients with history of recurrent venous thromboembolism (deep venous thrombosis or pulmonary embolism) or history of venous thromboembolism within 6 months will not be eligible
• Patients with history of active hepatitis B or C infection or ch