No cardiovascular disorders including:\r\n* Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening\r\n* Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) >  mm Hg systolic, or >  mm Hg diastolic despite optimal antihypertensive treatment within  days prior to registration\r\n* Any of the following within  months prior to registration:\r\n** Unstable angina pectoris\r\n** Clinically-significant cardiac arrhythmias\r\n** Stroke (including transient ischemic attack [TIA], or other ischemic event)\r\n** Myocardial infarction
Patients with clinically significant cardiovascular disease including: uncontrolled hypertension defined as systolic >  mm Hg or diastolic >  mm Hg; unstable angina or who have had a myocardial infarction within the past six months prior to registration; New York Heart Association (NYHA) grade II or greater congestive heart failure; serious cardiac arrhythmia requiring medication (this does not include asymptomatic atrial fibrillation with controlled ventricular rate); or CTCAE v., grade  or greater peripheral vascular disease (peripheral ischemia), defined as having at least brief (<  hour) episodes of ischemia managed non-surgically and without permanent deficit
Heart disease including congestive heart failure (New York Heart Association [NYHA] grade II or greater); unstable angina; prior myocardial infarction (non-ST-elevation myocardial infarction [NSTEMI] or ST-elevation myocardial infarction [STEMI]) within  months prior to study enrollment; hypertension with a systolic blood pressure of >  mm Hg or diastolic blood pressure of > mm Hg while on antihypertensive medication
Patients with impaired cardiac function or clinically significant cardiac diseases, including any of the following:\r\n* History or presence of serious uncontrolled ventricular arrhythmias\r\n* Any of the following within  months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, coronary artery bypass graft (CABG), congestive heart failure (CHF), cerebrovascular accident (CVA), transient ischemic attack (TIA), pulmonary embolism (PE)\r\n* Uncontrolled hypertension (defined as systolic blood pressure [SBP] >=  mm Hg or diastolic blood pressure [DBP] >=  mm Hg while on anti-hypertensive medications)
Patients with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study: \r\n* Impaired cardiac function or clinically significant cardiac diseases, including any of the following:\r\n** History or presence of serious uncontrolled ventricular arrhythmias\r\n** Clinically significant resting bradycardia\r\n** Left ventricular ejection fraction (LVEF) assessed by -dimensional (-D) echocardiogram (ECHO) < % or lower limit of normal (whichever is higher) or multiple gated acquisition scan (MUGA), < % or lower limit of normal (whichever is higher)\r\n** Any of the following within  months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, coronary artery bypass graft (CABG), congestive heart failure (CHF), cerebrovascular accident (CVA), transient ischemic attack (TIA), pulmonary embolism (PE)\r\n** Uncontrolled hypertension defined by a systolic blood pressure (SBP) >=  mm Hg and/or diastolic blood pressure (DBP) >=  mm Hg, with or without anti-hypertensive medication(s)\r\n* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) \r\n* Cirrhosis, chronic active hepatitis or chronic persistent hepatitis \r\n* Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)\r\n* Patients who are currently receiving anticoagulation treatment with therapeutic doses of warfarin; full-dose anti-coagulation with low molecular weight heparin is permitted\r\n* Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol
Significant medical history or unstable medical comorbidities, including but not limited to:\r\n* Heart disease including congestive heart failure (New York Heart Association [NYHA] grade II or greater); unstable angina; prior myocardial infarction (non-ST-elevation myocardial infarction [NSTEMI] or ST-elevation myocardial infarction [STEMI]) within  months prior to study enrollment; hypertension with a systolic blood pressure of >  mm Hg or diastolic blood pressure of >  mm Hg while on antihypertensive medication\r\n* Any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block\r\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under  years of age in first degree relatives or any concomitant medication known to prolong the QT interval\r\n* Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease\r\n* Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses\r\n* Active infection or ongoing antiviral medication for viral infections including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV). Screening for chronic conditions is not required. HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with osimertinib\r\n* Ongoing use of warfarin (injectable low-molecular weight heparins are permitted). Patients must be off warfarin for >  days prior to enrollment
Uncontrolled, significant concurrent or recent illness including, but not limited to, the following conditions: a. Cardiovascular disorders including i. congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening ii. concurrent uncontrolled hypertension defined as sustained blood pressure (BP) >  mm Hg systolic, or >  mm Hg diastolic despite optimal antihypertensive treatment within  days of the first dose of study treatment iii. any history of congenital long QT syndrome or iv. any of the following within  months before the first dose of study treatment: unstable angina pectoris, clinically-significant cardiac arrhythmias, stroke (including transient ischemic attack [TIA], or other ischemic event) within  days of the first dose of study treatment, myocardial infarction, clinically significant thromboembolic event within  days of randomization requiring therapeutic anticoagulation.
Clinically significant cardiac disease defined by any of the following criteria: a.) New York Heart Association (NYHA) class IV heart failure b.) N-terminal prohormone of brain natriuretic peptide (NT-ProBNP) >  ng/L c.) Symptomatic orthostatic hypotension with supine systolic blood pressure <  mm Hg d.) Unstable cardiac arrhythmia e.) Unstable angina f.) Myocardial infarction within the past  months
Significant cardiac history:\r\n* History of myocardial infarction or ischemic heart disease within  year before first study drug administration;\r\n* Uncontrolled arrhythmia;\r\n*History of congenital QT prolongation;\r\n* New York Heart Association class III or IV cardiac disease;\r\n* Uncontrolled hypertension: blood pressure consistently greater than  mm Hg systolic and  mm Hg diastolic in spite of antihypertensive medication
Patients with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:\r\n* Clinically significant cardiac diseases, including any of the following:\r\n** History or presence of serious uncontrolled ventricular arrhythmias \r\n** Clinically significant resting bradycardia\r\n** Any of the following within  months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, coronary artery bypass graft (CABG), congestive heart failure (CHF), cerebrovascular accident (CVA), transient ischemic attack (TIA), pulmonary embolism (PE)\r\n** Uncontrolled hypertension defined by a systolic blood pressure (SBP) ?  mmHg and/or diastolic blood pressure (DBP) ?  mm Hg, with or without anti-hypertensive medication(s)\r\n* Cirrhosis, chronic active hepatitis or chronic persistent hepatitis\r\n* Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)\r\n* Known diagnosis of any condition (i.e. post-hematopoietic or organ transplant, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, etc.) that requires chronic immunosuppressive therapy; usage of non-steroidal anti-inflammatory medications (NSAIDS) for the treatment of osteoarthritis and uric acid synthesis inhibitors for the treatment of gout are permitted; for questions, please consult the study chair\r\n* Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol
Clinically significant cardiovascular disease defined as follows: \r\n* Inadequately controlled hypertension (i.e., systolic blood pressure [SBP] >  mm Hg and/or diastolic pressure [DBP] >  mm Hg despite antihypertensive therapy) \r\n* History of cerebrovascular accident (CVA) within  months \r\n* Myocardial infarction or unstable angina within  months
PHASE II STUDY METASTATIC CASTRATE-RESISTANT PROSTATE CANCER COHORT  ELIGIBILITY CRITERIA (MEDI+O ONLY):\r\nThe patient has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\r\n* Cardiovascular disorders including:\r\n** Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening\r\n** Concurrent uncontrolled hypertension defined as sustained BP > mm Hg systolic, or >  mm Hg diastolic despite optimal anti-hypertensive treatment (BP must be controlled at screening)\r\n** Any history of congenital long QT syndrome\r\n** Any of the following within  months before the first dose of study treatment:\r\n*** Unstable angina pectoris\r\n*** Clinically-significant cardiac arrhythmias with the exception of asymptomatic atrial fibrillation controlled on therapy\r\n*** Stroke (including TIA, or other ischemic event)\r\n*** Myocardial infarction\r\n*** Thromboembolic event requiring therapeutic anti-coagulation (Note: subjects with a venous filter [e.g. vena cava filter] are not eligible for this study)\r\n*** Mean QT interval corrected for heart rate (QTc) >=  ms calculated from  electrocardiograms (ECGs) using Fridericias correction or other significant ECG abnormality noted within  days of treatment\r\n* Other clinically significant disorders such as:\r\n** Active infection requiring intravenous treatment within  days of starting protocol treatment\r\n** Serious non-healing wound/ulcer/bone fracture (excluding stable compression fracture) within  days before the first dose of study treatment
Uncontrolled intercurrent illness including, but not limited to:\r\n* Ongoing or active infection requiring parenteral antibiotics\r\n* Impairment of lung function (chronic obstructive pulmonary disease [COPD] > grade , lung conditions requiring oxygen therapy) or current dyspnea at rest\r\n* Symptomatic congestive heart failure (class III or IV of the New York Heart Association classification for heart disease)\r\n* Known left ventricular ejection fraction (LVEF) < %\r\n* Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within  months\r\n* Uncontrolled hypertension (systolic blood pressure >  mm Hg or diastolic blood pressure >  mm Hg, found on two consecutive measurements separated by a  or -week period despite adequate medical support)\r\n* Clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment [National Cancer Institute-Common Terminology Criteria for Adverse Events, version ., grade ])\r\n* Corrected QT using the Fridericia correction formula (QTcF) >=  msec on screening electrocardiogram (EKG)\r\n* Known history of QT/correct QT (QTc) prolongation or Torsades de Pointes (TdP)\r\n* ST depression or elevation of >= . mm in  or more leads\r\n* Diarrhea of any cause >= Common Terminology Criteria for Adverse Events (CTCAE) grade \r\n* Active autoimmune disease that is not controlled by nonsteroidal or steroidal (<  mg of prednisone per day) anti-inflammatory drugs or active inflammatory disease, including small or large intestine inflammation such as active Crohns disease or ulcerative colitis, which requires immunosuppressive therapy\r\n* Psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements including maintenance of a compliance/pill diary\r\n* Known history of chronic liver disease including cirrhosis, current alcohol abuse, or infection with hepatitis B virus or hepatitis C virus (active or carrier) or renal failure\r\n* Known history of chronic pancreatitis\r\n* Conditions that affect lymphocyte counts, such as human immunodeficiency virus (HIV) infection or immunosuppressive therapy
Ponatinib\r\n* History of acute pancreatitis within  year of study or history of chronic pancreatitis\r\n* History of alcohol abuse\r\n* Uncontrolled hypertriglyceridemia (triglycerides >  mg/dL)\r\n* Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:\r\n** Any history of myocardial infarction, stroke, or revascularization\r\n** Unstable angina or transient ischemic attack within  months prior to start of study treatment\r\n** Congestive heart failure within  months prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards within  months prior to enrollment\r\n** History of clinically significant (as determined by the treating physician) atrial arrhythmia\r\n** Any history of ventricular arrhythmia\r\n** Any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism\r\n* Uncontrolled hypertension (diastolic blood pressure >  mm Hg; systolic >  mm Hg); patients with hypertension should be under treatment on study entry to effect blood pressure control; taking medications that are known to be associated with torsades de pointes\r\n* Taking any medications or herbal supplements that are known to be strong inhibitors of CYPA within at least  days before the first dose of ponatinib\r\n* Ocular toxicity present as measured during a comprehensive eye exam
Uncontrolled hypertension (systolic >  mm Hg and/or diastolic >  mm Hg) or clinically significant (ie, active) cardiovascular disease, cerebrovascular accident/stroke, or myocardial infarction within  months prior to first study medication; unstable angina; congestive heart failure of New York Heart Association grade  or higher; or serious cardiac arrhythmia requiring medication. Subjects with uncontrolled hypertension should be medically managed on a stable regimen to control hypertension prior to study entry.
The subject has uncontrolled or significant intercurrent illness including, but not limited to,\r\nthe following conditions:\r\n* Cardiovascular disorders such as symptomatic congestive heart failure (CHF), uncontrolled hypertension defined as sustained blood pressure (BP) >  mm Hg systolic, or >  mm Hg diastolic despite optimal antihypertensive treatment (BP must be controlled at screening), unstable angina pectoris, clinically-significant cardiac arrhythmias, history of stroke (including transient ischemic attack [TIA], or other ischemic event) within  months of study treatment, myocardial infarction within  months of study treatment, history of thromboembolic event requiring therapeutic anticoagulation within  months of study treatment or main portal vein or vena cava thrombosis or occlusion; (Note: subjects with a venous filter [e.g. vena cava filter] are not eligible for this study)
No clinically significant cardiovascular disease, defined as one of the following:\r\n* Uncontrolled hypertension (blood pressure > / mm/Hg at the time of enrollment); patients with hypertension and blood pressure =< / mm Hg on stable antihypertensive regimen are eligible\r\n* History of myocardial infarction or unstable angina <  weeks prior to randomization\r\n* New York heart association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris\r\n* Grade II or greater peripheral vascular disease
This criterion applies only to the patients enrolled before August ,  and those enrolled after this date electing to receive bevacizumab; patients with clinically significant cardiovascular disease; this includes: \r\n* Patients with significant cardiac conduction abnormalities, i.e. PR interval > . seconds (sec) or nd or rd degree atrioventricular (AV) block\r\n* Uncontrolled hypertension, defined as systolic >  mm Hg or diastolic >  mm Hg\r\n* Myocardial infarction, cardiac arrhythmia or unstable angina <  months prior to registration\r\n* New York Heart Association (NYHA) grade II or greater congestive heart failure\r\n* Serious cardiac arrhythmia requiring medication\r\n* Grade II or greater peripheral vascular disease (exception: episodes of ischemia <  hours [hrs] in duration, that are managed non-surgically and without permanent deficit)\r\n* History of cerebrovascular attack (CVA) within six months
Significant medical co-morbidities as described below:\r\n* Cardiac disease:\r\n** Congestive heart failure > class II New York Heart Association (NYHA)\r\n** Unstable angina (anginal symptoms at rest), or new-onset angina (begun within the last  months), or myocardial infarction within the  months prior to enrollment, or\r\n** Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy\r\n** Known history of QTc prolongation or torsades de pointes\r\n* Grade  hypertension (systolic blood pressure [SBP] >=  mm Hg and/or diastolic blood pressure [DBP] >=  mm Hg despite maximal medical therapy)\r\n* Thrombotic, embolic, venous, or arterial events such as a cerebrovascular accident including transient ischemic attacks within the past  months\r\n* Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C\r\n* Previous or concurrent cancer that is distinct in primary site or histology from breast cancer within  years prior to enrollment EXCEPT cervical cancer in situ, treated non-melanoma skin cancers, superficial bladder tumors (Ta and Tis)
Uncontrolled hypertension (systolic >  mm Hg and/or diastolic >  mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction within  months prior to first study medication, unstable angina, congestive heart failure (CHF) of New York Heart Association (NYHA) grade II or higher, or serious cardiac arrhythmia requiring medication
Uncontrolled cardiovascular conditions of hypertension (systolic > mm Hg), angina pectoris, or cardiac dysrhythmia; or recent history of intracranial hemorrhage
Patients with clinically significant cardiovascular disease; this includes:\r\n* Poorly controlled hypertension (>  mm Hg and >  mm Hg for systolic and diastolic blood pressure [BP]) are ineligible\r\n* Myocardial infarction or unstable angina within  months prior to registration; New York Heart Association (NYHA) grade II or greater congestive heart failure \r\n* Cardiac arrhythmia requiring medication
Patients with clinically significant cardiovascular disease, including: \r\n* Uncontrolled hypertension, defined as systolic >  mm Hg or diastolic >  mm Hg\r\n* Myocardial infarction or unstable angina <  months prior to registration\r\n* New York Heart Association (NYHA) class II or higher congestive heart failure \r\n* Serious cardiac arrhythmia requiring medication\r\n* Cancer Therapy Evaluation Program (CTEP) CTCAE version ., grade  or higher peripheral ischemia (brief [<  hours (hrs)] episode of ischemia managed non-surgically and without permanent deficit) \r\n* Corrected QT (QTc) interval >  msec (CTCAE grade  or greater)
Cardiovascular disorders including:\r\n* Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening\r\n* Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) >  mm Hg systolic, or >  mm Hg diastolic despite optimal antihypertensive treatment within  days of the first dose of study treatment\r\n* Any of the following within  months before the first dose of study treatment:\r\n** Unstable angina pectoris\r\n** Clinically-significant cardiac arrhythmias\r\n** Stroke (including transient ischemic attack [TIA], or other ischemic event)\r\n** Myocardial infarction\r\n** Thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter [e.g. vena cava filter] are not eligible for this study)
PART B: Uncontrolled intercurrent illness including, but not limited to:\r\n* Ongoing or active infection requiring intravenous antibiotics\r\n* Psychiatric illness/social situations that would limit compliance with study requirements\r\n* Congestive heart failure, transient ischemic attack or unstable angina pectoris, within the  months prior to enrollment in part B of the study, or known left ventricular ejection fraction less than lower limit of normal per local institutional standards\r\n* History of clinically significant (as determined by the treating medical doctor [MD]) atrial arrhythmia \r\n* Uncontrolled hypertension (diastolic blood pressure [BP] >  mm Hg and/or systolic >  mm Hg)
Uncontrolled intercurrent illness including, but not limited to:\r\n* Ongoing or active infection requiring parenteral antibiotics\r\n* Impairment of lung function (chronic obstructive pulmonary disease [COPD] > grade , lung conditions requiring oxygen therapy)\r\n* Symptomatic congestive heart failure (class III or IV of the New York Heart Association classification for heart disease)\r\n* Known / previously documented left ventricular ejection fraction (LVEF) < % within  months of trial enrollment\r\n* Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within  months\r\n* Uncontrolled hypertension within  weeks of study initiation (systolic blood pressure >  mm Hg or diastolic blood pressure >  mm Hg, found on two consecutive measurements separated by a  or -week period despite adequate medical support)\r\n* Clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment [National Cancer Institute -Common Terminology Criteria for Adverse Events, version ., grade ])\r\n* QT interval corrected for heart rate using Fridericia's formula (QTcF) >=  msec on screening electrocardiogram (EKG)\r\n* Known history of QT/corrected QT interval (QTc) prolongation or torsades de pointes (TdP)\r\n* ST depression or elevation of >= . mm in  or more leads\r\n* Diarrhea of any cause >= Common Terminology Criteria for Adverse Events (CTCAE) grade \r\n* Psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements including maintenance of a compliance/pill diary\r\n* Patients with symptomatic brain metastases (patients with a history of brain metastases must be clinically stable for more than  weeks from completion of radiation treatment)\r\n* Patients with known history of chronic liver or renal failure\r\n* Patients with known history of chronic or acute pancreatitis
Uncontrolled intercurrent illness including, but not limited to:\r\n* Uncontrolled hypertension (for the purpose of this trial, well-controlled hypertension is defined as systolic blood pressure of <  mm Hg and diastolic pressure <  mm Hg)\r\n** NOTE: the use of anti-hypertensive medication to control hypertension is permitted, provided it is not noted as a prohibited med elsewhere in protocol\r\n* Ongoing or active infection\r\n* Symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or \r\n* Psychiatric illness/social situations that would limit compliance with study requirements
Patients with clinically significant cardiovascular disease. This includes: ) Uncontrolled hypertension, defined as systolic >  mm Hg or diastolic >  mm Hg; ) Myocardial infarction or unstable angina <  months prior to registration; ) New York Heart Association (NYHA) Grade II or greater congestive heart failure; ) Serious cardiac arrhythmia requiring medication. This does not include asymptomatic, atrial fibrillation with controlled ventricular rate
Myocardial infarction or arterial thromboembolic events within  months prior to baseline or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease, or a QTcB (corrected according to Bazett's formula) interval >  msec; serious uncontrolled cardiac arrhythmia grade II or higher according to NYHA; uncontrolled hypertension (systolic >  and/or diastolic >  mm Hg)
Known cardiac disease which precludes their ability to receive planned treatments:\r\n * Angina pectoris that requires the use of anti-anginal medication\r\n * History of documented congestive heart failure\r\n * Serious cardiac arrhythmia requiring medication\r\n * Severe conduction abnormality\r\n * Valvular disease with documented cardiac function compromise; and\r\n * Uncontrolled hypertension defined as blood pressure (BP) that is consistently > / on antihypertensive therapy at the time of registration; (patients with hypertension that is well controlled on medication are eligible)
Recent (<  months) myocardial infarction, unstable angina, coronary artery bypass surgery (CABG) or stent placement in the last  years, difficult-to-control congestive heart failure, uncontrolled hypertension (systolic blood pressure >  mm or a diastolic blood pressure [BP] >  mm under normal conditions and while on appropriate anti-hypertensive medications), or difficult-to-control cardiac arrhythmias
Clinically significant cardiac disease (class III, or IV of the New York Heart Association classification; unstable angina pectoris, myocardial infarction within  months or is post angioplasty or stenting within  months; clinically significant cardiac arrhythmia, or uncontrolled hypertension (i.e., systolic blood pressure >  mm Hg, diastolic blood pressure >  mmHg) despite anti-hypertensive medication;
Patients with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:\r\n* Impaired cardiac function or clinically significant cardiac diseases, including any of the following:\r\n** History or presence of serious uncontrolled ventricular arrhythmias\r\n** Clinically significant resting bradycardia\r\n** Left ventricular ejection fraction (LVEF) assessed by -dimensional (D) echocardiogram (ECHO) =< % or lower limit of normal (whichever is higher) or multiple gated acquisition scan (MUGA) < % or lower limit of normal (whichever is higher)\r\n** Any of the following within  months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, coronary artery bypass graft (CABG), congestive heart failure (CHF), cerebrovascular accident (CVA), transient ischemic attack (TIA), pulmonary embolism (PE)\r\n** Uncontrolled hypertension defined by a systolic blood pressure (SBP) >=  mm Hg and/or diastolic blood pressure (DBP) >=  mm Hg, with or without anti-hypertensive medication(s)\r\n* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)\r\n* Cirrhosis, chronic active hepatitis or chronic persistent hepatitis\r\n* Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)\r\n* Patients who are currently receiving anticoagulation treatment with therapeutic doses of warfarin\r\n* Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol
Clinically significant cardiovascular disease defined as follows:\r\n* Inadequately controlled hypertension (i.e., systolic blood pressure [SBP] >  mm Hg and/or diastolic blood pressure [DBP] >  mm Hg despite antihypertensive therapy)\r\n* History of cerebrovascular accident (CVA) within  months\r\n* Myocardial infarction or unstable angina within  months\r\n* New York Heart Association classification II, III, or IV cardiovascular disease\r\n* Serious and inadequately controlled cardiac arrhythmia\r\n* Significant vascular disease (i.e., aortic aneurysm, history of aortic dissection)\r\n* Clinically significant peripheral vascular disease
Cardiovascular disorders including\r\n* Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening\r\n* Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) >=  mm Hg systolic, or >=  mm Hg diastolic despite optimal antihypertensive treatment (Note: if there is any BP measurement that is performed within the screening period that is <  mm Hg systolic and <  mm Hg diastolic, then BP does not meet definition of sustained)\r\n* Any congenital history of long QT syndrome\r\n* Any of the following within  months before the first dose of study treatment:\r\n** Unstable angina pectoris\r\n** Clinically-significant cardiac arrhythmias\r\n** Stroke (including transient ischemic attack [TIA], or other ischemic event)\r\n** Myocardial infarction\r\n** Thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter [e.g. vena cava filter] are not eligible for this study)
Patients with clinically significant cardiovascular or cerebrovascular disease:\r\n* History of cerebrovascular accident or transient ischemic attack within past  months\r\n* Uncontrolled hypertension, defined as blood pressure > / mm Hg or systolic blood pressure (BP) >  mm Hg if diastolic blood pressure <  mm Hg, on at least  repeated determinations on separate days within past  months\r\n* Myocardial infarction, coronary artery bypass graft (CABG) or unstable angina within the past  Months\r\n* New York Heart Association grade III or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris within past  months\r\n* Clinically significant peripheral vascular disease within past  months\r\n* Pulmonary embolism, deep vein thrombosis (DVT), or other thromboembolic event within past  months
Impaired cardiac function or clinically significant cardiac diseases, including any of the following:\r\n* History or presence of serious uncontrolled ventricular arrhythmias\r\n* Clinically significant resting bradycardia\r\n* Ongoing cardiac dysrhythmias, atrial fibrillation, or prolongation of corrected QTc interval to >  msec\r\n\t* Left ventricular ejection fraction (LVEF) assessed by -dimensional (-D) echocardiogram (ECHO) < % or lower limit of normal (whichever is the higher), or -D multiple gated acquisition scan (MUGA) < % or lower limit of normal (whichever is the higher)\r\n* Any of the following =<  days prior to starting study drug: myocardial infarction (MI), severe/unstable angina, coronary artery bypass graft (CABG), congestive heart failure (CHF), cerebrovascular accident (CVA), transient ischemic attack (TIA)\r\n* Uncontrolled hypertension defined by a systolic blood pressure (SBP) >=  mm Hg and/or diastolic (D)BP >=  mm Hg, with or without anti-hypertensive medication(s); initiation or adjustment of antihypertensive medication(s) is allowed prior to study entry
Patients must not have cardiovascular risk factors including unstable angina, history of documented myocardial infarction or cerebrovascular accident, coronary artery bypass surgery, or New York Heart Association class III or IV heart failure; patients must not have known uncontrolled hyperlipidemia (defined as low-density lipoprotein cholesterol [LDL-C] >=  mg/dL or triglycerides >=  mg/dL) within the last  years prior to registration or uncontrolled high blood pressure (systolic blood pressure >  mm Hg) within  days prior to registration
Within the past month:\r\n* Heart attack\r\n* Unstable or stable angina (cardiac chest pain)\r\n* Left main coronary artery disease\r\n* Symptomatic heart failure\r\n* Uncontrolled hypertension (systolic blood pressure [SBP] >  mm Hg or diastolic blood pressure [DBP] > mm Hg)\r\n* Severe valvular heart disease\r\n* Uncontrolled metabolic disease (diabetes with fasting blood sugar [BS] >  mg/dl, thyrotoxicosis, myxedema)\r\n* Aortic aneurism (>  mm diameter) or aortic dissection\r\n* Hypertrophic obstructive cardiomyopathy
CONTROL (HEALTHY) GROUP: Within the past month:\r\n* Heart attack\r\n* Unstable or stable angina (cardiac chest pain)\r\n* Left main coronary artery disease\r\n* Symptomatic heart failure\r\n* Uncontrolled hypertension (SBP >  mm Hg or DBP > mm Hg)\r\n* Severe valvular heart disease\r\n* Uncontrolled metabolic disease (diabetes with fasting BS >  mg/dl, thyrotoxicosis, myxedema)\r\n* Aortic aneurism (>  mm diameter) or aortic dissection\r\n* Uncontrolled slow or fast heart rhythm causing symptoms or hemodynamic compromise\r\n* Hypertrophic obstructive cardiomyopathy
Active cardiac disease including any of the following:\r\n* Severe congestive heart failure (class IV in accordance with the classification of the New York Heart Association)\r\n* Unstable angina\r\n* Severe arrhythmia (i.e. ventricular tachycardia, flutter fibrillation; ventricular premature complexes occurring close to the preceding T- wave, multifocal complexes)\r\n* Myocardial infarction within  days prior to the date of proposed Definity administration\r\n* Uncontrolled systemic hypertension (systolic blood pressure [BP] >  mm Hg and/or diastolic BP >  mm Hg) despite optimal medical management