Patient has clinically significant, uncontrolled heart disease and/or recent events including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within  months prior to treatment start\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Patient has a left ventricular ejection fraction (LVEF) < % as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* History of any cardiac arrhythmias, eg., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within  months prior to treatment start\r\n* Family history of corrected QT interval (QTc) prolongation or of unexplainable sudden death at <  years of age\r\n* On screening  lead electrocardiogram (ECG), any of the following cardiac parameters: bradycardia (heart rate <  at rest), tachycardia (heart rate >  at rest), PR interval >  msec, QRS interval >  msec, or Fridericia corrected QT (QTcF) >  msec; congenital long QT syndrome or family history of long QT syndrome\r\n* Systolic blood pressure (SBP) >  mmHg or <  mmHg\r\n* Bradycardia (heart rate <  at rest), by ECG or pulse, at screening
Clinically significant active cardiac disease, uncontrolled heart disease and/or a history of cardiac dysfunction including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within  months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Patient has a left ventricular ejection fraction (LVEF) < % as determined by echocardiogram (ECHO) \r\n* History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within  months of screening\r\n* Long QT syndrome or known family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: \r\n** Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n** Concomitant use of medication(s) with a known risk to prolong the QT interval and/or days prior to starting study drug) or replaced by safe alternative medication\r\n* -lead electrocardiogram (ECG), any of the following cardiac parameters:\r\n** QTc >  msec\r\n* Hypertension defined as: \r\n** Patients - years of age with blood pressure that is > th percentile for age, height and gender at the time of enrollment \r\n*** The normal blood pressure by height, age and gender tables can be accessed in the Generic Forms section of the PBTC members webpage\r\n** Patients who are >=  years of age with blood pressure > / mm of Hg at the time of enrollment\r\n* Note: if a blood pressure (BP) reading prior to enrollment does not meet parameters, blood pressure should be rechecked and documented to be within eligibility range prior to patient enrollment
Participants with uncontrolled intercurrent illness including, but not limited to:\r\n* Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:\r\n** History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within  months prior to screening\r\n** History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n** Documented cardiomyopathy\r\n** Left ventricular ejection fraction (LVEF) =< % as determined by multiple-gated acquisition (MUGA) scan or echocardiogram (ECHO) within six months prior to beginning protocol therapy\r\n** Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block)\r\n** Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:\r\n*** Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n*** Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within  half-lives or  days prior to starting study drug) or replaced by safe alternative medication\r\n** Systolic blood pressure (SBP) >  mmHg or <  mmHg at screening\r\n** Impairment of gastrointestinal function or who have gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea or malabsorption syndrome)\r\n** Patient with liver disease and Child-Pugh score B or C
Clinically significant, uncontrolled heart disease and/ or cardiac repolarization abnormalities including any of the following:\r\n* History of unstable angina pectoris, symptomatic pericarditis, myocardial infarction, coronary artery bypass grafting or coronary angioplasty =<  months prior to registration\r\n* History of documented congestive heart failure (New York Heart Association functional classification III - IV)\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < % as determined by echocardiogram (ECHO)\r\n* Clinically significant cardiac arrhythmias (e.g ventricular tachycardia) , left bundle branch block, high-grade atrioventricular (AV) block (e.g bifascucular block, Mobitz type II and third degree AV block)\r\n* Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:\r\n** Risk factors for torsades de pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n** Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause torsades de pointe that cannot be discontinued (within  half-lives or =<  days prior to registration) or replaced by safe alternative medication\r\n** Inability to determine the QT interval on screening (QTcF, using Fridericia s correction)
Participants who have clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within  months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g. bifascicular block, Mobitz type II) and third-degree AV block\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < % as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following\r\n** Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n** Inability to determine the QT interval on screening (QTcF, using Fridericias correction)\r\n* Systolic blood pressure (SBP) >  mmHg or <  mmHg at screening
Clinically significant, uncontrolled heart disease and/or recent events including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within  months prior to screening;\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV);\r\n* Documented cardiomyopathy;\r\n* Patient has a left ventricular ejection fraction < % as determined by multi-gated acquisition (MUGA) scan or echocardiography\r\n(ECHO) at screening;\r\n* History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrthymias, or conduction abnormality within  months of screening;\r\n* Bradycardia (heart rate <  at rest), by electrocardiography (ECG) or pulse, at screening;\r\n* Congenital long QT syndrome or family history of long QT syndrome;\r\n* Systolic blood pressure (SBP) >  or <  mm Hg
Clinically significant, uncontrolled heart disease and/or recent events including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) or symptomatic pericarditis within  months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Patient has a left ventricular ejection fraction (LVEF) < % as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) obtained during screening\r\n* History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within  months of screening; patients with rate-controlled atrial fibrillation or flutter are permitted\r\n* Bradycardia (heart rate <  bpm at rest), by electrocardiography (ECG) or pulse, at screening\r\n* Congenital long QT syndrome or family history of long QT syndrome\r\n* Any of the following abnormalities on screening -lead ECG:\r\n** QTcF (Fridericias formula) >  msec\r\n** Bradycardia (heart rate <  bpm at rest)\r\n** PR interval >  msec\r\n** QRS interval >  msec\r\n* Documented cardiomyopathy\r\n* Systolic blood pressure >  mmHg or <  mmHg at screening
Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:\r\n* Any history of myocardial infarction\r\n* Any history of clinically significant (as determined by the treating physician) atrial arrhythmia\r\n* Any history of ventricular arrhythmia\r\n* Any history of cerebrovascular accident or transient ischemic attack (TIA)\r\n* Any history of peripheral arterial occlusive disease requiring revascularization\r\n* Unstable angina within  months prior to enrollment\r\n* Congestive heart failure within  months prior to enrollment\r\n* Venous thromboembolism including deep venous thrombosis or pulmonary embolism within  months prior to enrollment\r\n* Unacceptable screening baseline cardiovascular assessment:\r\n** Baseline multi gated acquisition scan (MUGA) (to be done within  days of registration) or echocardiogram demonstrating left ventricular ejection fraction (LVEF) <  %\r\n** Corrected QT (QTc) >=  msec on screening electrocardiogram (ECG) (using the QTc Fridericia [QTcF] formula)
Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:\r\n* History of angina pectoris, symptomatic pericarditis, coronary artery bypass graft (CABG) or myocardial infarction within  months prior to study entry\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < % as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening
History of cardiac failure, significant/symptomatic bradycardia, long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome or any of the following:\r\n* Known risk to prolong the QT interval or induce torsades de pointes\r\n* Uncorrected hypomagnesemia or hypokalemia\r\n* Systolic blood pressure (SBP) >  mmHg or <  mmHg\r\n* Bradycardia (heart rate <  at rest), by electrocardiogram (ECG) or pulse\r\n* On screening, inability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF >  (based on a mean of  ECGs)
Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality,\r\nincluding any of the following:\r\n* History of myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft (CABG) within  months prior to study entry\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < % as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:\r\n** Risk factors for torsades de pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n** Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause torsades de pointe that cannot be discontinued or replaced by safe alternative medication (e.g. within  half-lives or  days prior to starting study drug)\r\n** Inability to determine the QTcF interval\r\n* Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block
History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), untreated coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), myocardial infarction or atrial thrombotic events within the past  months, severe unstable angina, New York Heart Association Class III and IV heart disease or depressed left ventricular ejection fraction (LVEF; previously documented LVEF < % without documentation of recovery), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome
Uncontrolled or significant cardiovascular disease, including any of the following:\r\n* Corrected QT (QTc) interval >  msec (mean value and manually verified) at  or more time points within a  hour period if necessary\r\n* Diagnosed or expected congenital long QT syndrome\r\n* Concurrent congestive heart failure, prior history of class III/IV cardiac disease (New York Heart Association)\r\n* Left ventricular ejection fraction < %\r\n* Prior history of cardiac ischemia or cardiac arrhythmia within the last  months; coronary angioplasty or stenting in the previous  months\r\n* Any history of second or third degree heart block (may be eligible if the subject currently has a pacemaker)\r\n* Uncontrolled hypertension defined as inability to maintain blood pressure below the limit of / mmHg\r\n* Known pulmonary hypertension
Clinically significant cardiac disease or impaired cardiac function, such as:\r\n* Congestive heart failure (CHF) requiring treatment (New York Heart Association [NYHA] grade >= ) or left ventricular ejection fraction (LVEF) < % as determined by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* History or current evidence of clinically significant cardiac arrhythmias, atrial fibrillation and/or conduction abnormality, e.g. congenital long QT syndrome, high-grade/complete atrioventricular (AV)-blockage\r\n* Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft [CABG], coronary angioplasty, or stenting), <  months prior to screening\r\n* QT interval adjusted according to Fredericia (QTcF) >  msec on screening electrocardiogram (ECG)
Uncontrolled angina, congestive heart failure, myocardial infarction (MI) (within last  months), congenital long QT syndrome, history of clinically significant ventricular arrhythmia, prolonged QTcF interval on pre-entry electrocardiogram (EKG) (greater than normal range)
Patients with the following cardiovascular abnormalities:\r\n* Corrected QT interval (QTc) >  msec within  days prior to registration for protocol therapy; NOTE: if QTc is >  and ?  msec, subject to local cardiology review and approval, the patient may be enrolled if the QTc elevation is deemed clinically insignificant\r\n* Acute cardiovascular events within  months prior to CD: stroke (transient ischemic attack permitted), acute coronary syndrome, peripheral arterial obstruction, clinically significant arrhythmias (e.g., such as paroxysmal atrial fibrillation/atrial flutter, sick sinus syndrome, second or third degree atrio-ventricular blockade); a cardiology consultation may be obtained to clarify clinical significance\r\n* Clinical cardiac heart failure of New York Heart Association class III or IV or left ventricular ejection fraction (LVEF) < % as assessed by echocardiogram at screening
Positive risk assessment for cardiovascular disease including prior anthracycline cumulative dose more than % above recommended non-cardiotoxic levels, left ventricular ejection fraction (LVEF) <%, valvular heart disease, or severe hypertension, (see Table ). Cardiac subjects with a New York Heart Association (NYHA) classification of  or  will be excluded. (Cardiology consultation should be requested if any question arises about cardiac function.) This also includes subjects with baseline QT/QTc interval > msec, a history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) and using concomitant medications that significantly prolong the QT/QTc interval.
Clinically significant uncontrolled heart disease and/or recent cardiac event within  months prior to enrollment, such as:\r\n* History of angina pectoris, symptomatic pericarditis, or myocardial infarction\r\n* Left ventricular ejection fraction (LVEF) < % as determined by echocardiogram (ECHO) or multi gated acquisition (MUGA) scan\r\n* History or presence of any cardiac arrhythmias, e.g. ventricular, supraventricular, nodal arrhythmias or conduction abnormality; stable atrial fibrillation within  months prior to randomization is permitted\r\n* Presence of unstable atrial fibrillation (ventricular response rate >  beats per minute [bpm]); NOTE: patients with stable atrial fibrillation\r\n* Resting heart rate <  bpm\r\n* Complete left bundle branch block (LBBB), bifascicular block\r\n* Congenital long QT syndrome\r\n* Any clinically significant ST segment and/or T-wave abnormalities\r\n* Corrected QT (QTcF) >  msec for males and females using Fridericias correction on screening electrocardiogram (ECG) by mean value of triplicate ECGs\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Uncontrolled hypertension defined by a systolic blood pressure (SBP) >=  mmHg and/or diastolic blood pressure (DBP) >=  mmHg with or without antihypertensive medication; NOTE: initiation or adjustment of antihypertensive medication(s) is allowed prior to screening\r\n* Other clinically significant heart disease or vascular disease
Uncontrolled intercurrent illness including, but not limited to:\r\n* Malabsorption syndrome significantly affecting gastrointestinal function\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* Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within  months\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* Fridericia's correction formula (QTcF) >=  msec on screening electrocardiography (EKG)\r\n* Known history of clinically significant QT/corrected 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* Psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements including maintenance of a compliance/pill diary\r\n* Symptomatic brain metastases (patients with a history of brain metastases must be clinically stable for more than  weeks from completion of radiation treatment and be off steroids)\r\n* Known history of chronic liver or chronic renal failure\r\n* Poor wound healing capacity
Cardiac conditions as follows: uncontrolled hypertension (blood pressure [BP] >= / mmHg despite medical therapy); acute coronary syndrome within  months prior to starting treatment; uncontrolled angina - Canadian Cardiovascular Society grade II-IV despite medical therapy; symptomatic heart failure New York Heart Association (NYHA) class II-IV, prior or current cardiomyopathy, or severe valvular heart disease; prior or current cardiomyopathy including but not limited to the following: known hypertrophic cardiomyopathy or known arrhythmogenic right ventricular cardiomyopathy; previous moderate or severe impairment of left ventricular systolic function (left ventricular ejection fraction [LVEF] < % on echocardiography or equivalent on multigated acquisition [MUGA]) even if full recovery has occurred; severe valvular heart disease; baseline LVEF below the lower limit of normal (LLN) measured by echocardiogram (ECHO) or institutions LLN for MUGA; atrial fibrillation with a ventricular rate >  bpm on electrocardiogram (ECG) at rest; corrected QT interval by Fridericia (QTcF) >  ms on two or more timepoints or other factors that increase the risk of QT prolongation such as family history of long QT syndrome
Patients with the following cardiac conditions are excluded:\r\n* Uncontrolled hypertension (adults: blood pressure [BP] of >= / despite medical support/management; participants  years of age and younger should have a blood pressure =< th percentile for age, height and gender; preexisting hypertension in adults should be controlled [either with pharmacological or non-pharmacological methods] at the time of enrollment)\r\n* Acute coronary syndrome within  months prior to starting treatment\r\n* Uncontrolled angina  Canadian Cardiovascular Society grade II-IV despite medical support/management\r\n* Heart failure New York Heart Association (NYHA) class II or above\r\n* Prior or current cardiomyopathy including but not limited to the following:\r\n** Known hypertrophic cardiomyopathy\r\n* Known arrhythmogenic right ventricular cardiomyopathy\r\n* Baseline left ventricular ejection fraction (LVEF) =< %\r\n* Previous moderate or severe impairment of left ventricular systolic function (LVEF < % on echocardiography or equivalent on Multi-Gated Acquisition Scan [MUGA]) even if full recovery has occurred\r\n* Severe valvular heart disease\r\n* Atrial fibrillation with a ventricular rate >  beats per minute (bpm) on electrocardiogram (ECG) at rest\r\n* QT interval corrected according to Fridericias formula (QTcF) interval >  msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) are excluded.; the use of medication(s) that can prolong QTc interval is prohibited while treated on this study
Any one of the following currently or in the previous  months:\r\n* Myocardial infarction\r\n* Congenital long QT syndrome\r\n* Torsades de points\r\n* Arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), and left anterior hemiblock (bifascicular block)\r\n* Unstable angina, coronary/peripheral artery bypass graft\r\n* Symptomatic congestive heart failure (congestive heart failure [CHF] New York Heart Association class III or IV)\r\n* Cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism or other clinical significant episode of thrombo-embolic disease (Cases must be discussed in detail with study chair to judge eligibility; anticoagulation (heparin only, no vitamin-K antagonists or factor Xa inhibitors) will be allowed if indicated)\r\n* Ongoing cardiac dysrhythmias of NCI CTCAE grade >= , atrial fibrillation of any grade, or QT correction using Fridericia's correction formula (QTcF) interval >  msec at screening (except in case of right bundle branch block, these cases must be discussed with sponsors medical monitor)
Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:\r\n* New York Heart Association functional classification III-IV\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < % as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block)\r\n* Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesaemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia; concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within  half-lives or  days prior to starting study drug) or replaced by safe alternative medication\r\n* Inability to determine the QT interval on screening (QTcFusing Fridericias correction)\r\n* Systolic blood pressure (SBP) >  mmHg or <  mmHg at screening
Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality including any of the following:\r\n* History of myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft (CABG) within  months prior to study entry\r\n* Documented cardiomyopathy\r\n* Patient has a known left ventricular fraction (LVEF) < % as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* Long QT syndrome or family history of long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:\r\n** Risk factors for torsades de pointe (TdP) including uncorrected hypokalemia or hypomagnesaemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n** Concomitant medications(s) with a known risk to prolong the QT interval and/or known to cause torsades de pointe that cannot be discontinued or replaced by safe alternative medication (e.g. within  half-lives or  days prior to starting study drug)\r\n** Inability to determine the corrected QT (QTc) interval\r\n* Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block)
Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within  months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < % as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block)\r\n* Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:\r\n* Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n* Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within  half-lives or  days prior to starting study drug) or replaced by safe alternative medication\r\n* Inability to determine the QT interval on screening (QTcF, using Fridericias correction)\r\n* Systolic blood pressure (SBP) >  mmHg or <  mmHg at screening
Cardiac conditions as follows:\r\n* Uncontrolled hypertension (blood pressure [BP] >= / despite optimal therapy)\r\n* Heart failure New York Heart Association (NYHA) class II or above\r\n* If NYHA class I heart failure, left ventricular ejection fraction (LVEF) by multi-gated acquisition scan (MUGA) or echocardiogram (ECHO) is less than %\r\n* Unstable ischemic heart disease (myocardial infarction within  months prior to starting treatment, or angina requiring use of nitrates more than once weekly)\r\n* Mean resting corrected QT (QTc) interval using the Fridericia formula (QTcF) >  msec/male and >  msec/female (as calculated per institutional standards) obtained from  electrocardiograms (ECGs) - minutes apart at study entry, or congenital long QT syndrome\r\n* Patients with significant ventricular or supraventricular arrhythmias and patients with cardiac conduction abnormalities that are not controlled (e.g. with a pacemaker or medication)
Known cardiac disorder, including:\r\n* Uncontrolled hypertension (blood pressure [BP] of >= / despite medical support/management)\r\n* Acute coronary syndrome within  months prior to starting treatment\r\n* Uncontrolled angina  Canadian Cardiovascular Society grade II-IV despite medical support/management\r\n* Heart failure New York Heart Association (NYHA) class II or above\r\n* Prior or current cardiomyopathy including but not limited to the following:\r\n** Known hypertrophic cardiomyopathy\r\n* Known arrhythmogenic right ventricular cardiomyopathy\r\n* Baseline left ventricular ejection fraction (LVEF) =< %\r\n* Previous moderate or severe impairment of left ventricular systolic function (LVEF < % on echocardiography or equivalent on multi-gated acquisition scan [MUGA])\r\neven if full recovery has occurred\r\n* Severe valvular heart disease\r\n* Atrial fibrillation with a ventricular rate >  beats per minute (bpm) on electrocardiography (ECG) at rest\r\n* Fridericia's correction formula (QTcF) interval >  msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) are excluded; the use of medication(s) that can prolong corrected QT (QTc) interval is prohibited while treated on this study
Significant cardiovascular disease, including:\r\n* Symptomatic left ventricular dysfunction or baseline left ventricular ejection fraction (LVEF) by multigated acquisition scan (MUGA) or echocardiogram (ECHO) of =< lower limit of institutional normal (LVEF < %)\r\n* Patients with marked baseline prolongation of QT/QTc interval (QTc interval >  msec for males or >  msec for females)\r\n* Uncontrolled hypertension: systolic blood pressure of >  mmHg or diastolic blood pressure of >  mmHg documented on  consecutive measurements taken at least  hours apart\r\n* Myocardial infarction, severe angina, or unstable angina within  months prior to administration of first dose of study drug\r\n* History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation)\r\n* Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)\r\n* Coronary or peripheral artery bypass graft within  months of screening\r\n* History of class III or IV congestive heart failure as defined by the New York Heart Association
Patient has active cardiac disease or a history of cardiac dysfunction including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within  months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < % as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g. bifascicular block, Mobitz type II and third-degree AV block)\r\n* Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:\r\n** Risk factors for torsades de pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n** Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause torsades de pointe that cannot be discontinued (within  half-lives or  days prior to starting study drug) or replaced by safe alternative medication\r\n** Inability to determine the QT interval on screening (QTcF, using Fridericias correction)\r\n* Systolic blood pressure (SBP) >  mmHg or <  mmHg at screening
Uncontrolled intercurrent illnesses including, but not limited to unstable angina or uncontrolled cardiac arrhythmia, chronic liver disease, complete left bundle branch block, obligate use of a cardiac pacemaker, ST depression of >  mm in two or more leads and/or T wave inversions in two or more contiguous leads, congenital long QT syndrome, history of or presence of significant ventricular or atrial tachyarrhythmias, clinically significant resting bradycardia (<  beats per minute), corrected QT (QTc) >  ms on screening electrocardiogram that could jeopardize the patients ability to receive the chemotherapy described in the protocol safely
Patient has known clinically significant cardiac disease or impaired cardiac function, such as:\r\n* Congestive heart failure requiring treatment (New York Heart Association grade >= ), left ventricular ejection fraction (LVEF) < % as determined by multigated acquisition (MUGA) scan or ECHO. \r\n* History or current evidence of clinically significant cardiac arrhythmias, atrial fibrillation, and/or conduction abnormality, e.g., congenital long QT syndrome, high-grade/complete arteriovenous blockage.\r\n* Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft, coronary angioplasty, or stenting) <  months prior to screening.
Patient has clinically significant cardiac disease or impaired cardiac function, such as:\r\n* Congestive heart failure (CHF) requiring treatment (New York Heart Association [NYHA] Grade >= ), left ventricular ejection fraction (LVEF) < % as determined by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* History or current evidence of clinically significant cardiac arrhythmias, atrial fibrillation and/or conduction abnormality, e.g. congenital long QT syndrome, high-grade/complete atrioventricular (AV)-blockage; patients with asymptomatic and rate-controlled atrial fibrillation are not excluded\r\n* Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft (CABG), coronary angioplasty, or stenting), <  months prior to screening
Significant cardiac disease or abnormality, including any one of the following:\r\n* Left ventricular ejection fraction < % at screening (assessed by echocardiography, cardiac MRI or multigated acquisition [MUGA])\r\n* Corrected QT Fridericia's correction formula (QTcF) >  ms on screening electrocardiogram (ECG), or a clinically-relevant ECG abnormality\r\n* Congenital long QT syndrome\r\n* History of sustained ventricular tachycardia, ventricular fibrillation, or torsades de pointes\r\n* Presence of atrial fibrillation with tachyarrhythmia (ventricular response rate >  beats per minute [bpm])\r\n* Bradycardia (heart rate <  bpm)\r\n* Complete left bundle branch block\r\n* Bifascicular block (complete right bundle branch block and anterior or posterior left hemiblock)\r\n* Myocardial infarction, acute coronary syndrome (including unstable angina), coronary revascularization procedures, or coronary arterial bypass grafting within the  months prior to starting study drug\r\n* Cardiac troponin (either troponin T or troponin I) > ULN\r\n* Congestive heart failure of New York Heart Association class III or IV\r\n* Unstable angina pectoris
Patients with the following cardiac conditions are excluded:\r\n* Uncontrolled hypertension (blood pressure [BP] of >= / despite medical support/management)\r\n* Acute coronary syndrome within  months prior to starting treatment\r\n* Uncontrolled angina  Canadian Cardiovascular Society grade II-IV despite medical support/management\r\n* Heart failure New York Heart Association (NYHA) class II or above\r\n* Prior or current cardiomyopathy (within  months) including but not limited to the following:\r\n** Known hypertrophic cardiomyopathy\r\n** Known arrhythmogenic right ventricular cardiomyopathy\r\n** Abnormal ejection fraction (echocardiogram [ECHO]) =< % (if a range is given then the upper value of the range will be used) or cardiac MRI\r\n** Previous moderate or severe impairment of left ventricular systolic function (left ventricular ejection fraction [LVEF] < % on echocardiography or equivalent on multi-gated acquisition scan [MUGA]) even if full recovery has occurred; echocardiogram (Echo) and additional cardiac studies not indicated unless clinically symptomatic or patient has significant cardiac history\r\n** Severe valvular heart disease\r\n** Atrial fibrillation with a ventricular rate >  beats per minute (bpm) on electrocardiogram (ECG) at rest\r\n** Fridericia's corrected QT interval (QTcF) >=  msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) are excluded; the use of medication(s) that can prolong QTc interval is prohibited while treated on this study
Patients has any of the following cardiac abnormalities:\r\n* Symptomatic congestive heart failure\r\n** History of documented congestive heart failure (New York Heart Association functional classification III-IV), documented cardiomyopathy\r\n** Left ventricular ejection fraction < % as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) \r\n* Myocardial infarction =<  months prior to enrollment \r\n* Unstable angina pectoris\r\n* Serious uncontrolled cardiac arrhythmia\r\n* Symptomatic pericarditis\r\n* Corrected QT interval using Fridericia's formula (QTcF) >  msec on the screening electrocardiogram (ECG) (using the QTcF formula)
Clinically significant, uncontrolled heart disease and/or a recent events including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within  months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Patient has a Left Ventricular Ejection Fraction (LVEF) < % as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, conduction abnormality in the previous  months of screening\r\n* Congenital long QT syndrome or family history of long QT syndrome\r\n* Sustained systolic blood pressure (SBP) >  mmHg or <  mmHg at screening; must be corrected or controlled prior to starting study\r\n* Bradycardia (heart rate <  at rest) by electrocardiogram (ECG) or pulse, at screening\r\n* On screening inability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF >  msec (using Fridericias correction); all as determined by screening ECG (mean of triplicate ECGs)
Clinically significant, uncontrolled heart disease and/ or a history of cardiac dysfunction including any of the following:\r\n* History of unstable angina pectoris, symptomatic pericarditis, myocardial infarction, coronary artery bypass grafting or coronary angioplasty within  months prior to study entry\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Patient has a left ventricular ejection fraction (LVEF) < % as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* History of clinically significant ventricular arrhythmia and/or conduction delays within  months of screening\r\n* Systolic blood pressure >  mmHg or <  mmHg\r\n* Congenital long QT syndrome or family history of long QT syndrome\r\n* Bradycardia (heart rate <  at rest) by electrocardiogram (ECG) or pulse at screening.
Clinically significant cardiac disease or impaired cardiac function, such as:\r\n* Congestive heart failure (CHF) requiring treatment (New York Heart Association [NYHA] grade >= ), left ventricular ejection fraction (LVEF) < % as determined by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* History or current evidence of unstable, clinically significant cardiac arrhythmias or patients that require medications with a narrow therapeutic window, atrial fibrillation and/or conduction abnormality, e.g. congenital long QT syndrome, high-grade/complete atrioventricular (AV)-blockage\r\n* Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft [CABG], coronary angioplasty, or stenting), <  months prior to screening
History of any of the following cardiovascular events or conditions within the past \n             months prior to enrolment: myocardial infarction, unstable angina, cerebrovascular\n             accident or transient ischemic attack, New York Heart Association Class ? II chronic\n             heart failure, hypokalemia, significant arrhythmia*; QTc interval > msec or use of\n             drugs that prolong the QT interval at screening; family history of long QT\n             syndrome.(* Significant arrhythmias are defined as symptoms of syncope or severe\n             palpitations (palpitations requiring referral to cardiac monitoring), or ECG findings\n             of supraventricular tachycardia (including ventricular fibrillation) or ventricular\n             ectopy (ventricular premature depolarization).
Cardiovascular criteria will exclude a patient from participation in the study will include:\r\n* Screening electrocardiogram (ECG) with a QTc >  msec;\r\n* Patients with congenital long QT syndrome; \r\n* History or presence of sustained ventricular tachycardia;\r\n* Any history of ventricular fibrillation or torsades de pointes;\r\n* Bradycardia defined as heart rate (HR) <  bpm;\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block);\r\n* Patients with myocardial infarction or unstable angina <  months prior to starting study drug;\r\n* Congestive heart failure (CHF) New York (NY) Heart Association class III or IV;\r\n* Patients with an ejection fraction =< % assessed by multi gated acquisition scan (MUGA) or echocardiogram (ECHO) scan within  days of day \r\n* Poorly controlled hypertension
Clinically significant cardiac disease or impaired cardiac function, such as:\r\n* Baseline left ventricular ejection fraction (LVEF) < % on baseline echocardiogram or multi gated acquisition scan (MUGA)\r\n* Congestive heart failure requiring treatment (e.g., New York Heart Association class II, III or IV) within  months prior to screening\r\n* Acute coronary syndromes <  months prior to screening (including myocardial infarction, unstable angina, coronary artery bypass graft, coronary angioplasty, or stenting)\r\n* Uncontrolled arterial hypertension defined by blood pressure > / mm Hg at rest (average of  consecutive readings)\r\n* History or current evidence of unstable, clinically significant cardiac arrhythmias\r\n* Patients that require medications with a narrow therapeutic window\r\n* Clinically significant conduction abnormality, e.g. congenital long QT syndrome, high-grade/complete atrioventricular (AV)-blockage\r\n* Corrected QT interval (QTc) >  msec on screening electrocardiogram (ECG)
Clinically significant, uncontrolled heart disease or cardiac repolarization abnormalities and/or recent events including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within  months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < % as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g. bifascicular block, Mobitz type II and third-degree AV block) long QT syndrome or family history of long QT syndrome\r\n* Idiopathic sudden death or congenital long QT syndrome\r\n* Risk factors for torsades de pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia\r\n* Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause torsades de pointe that cannot be discontinued (within  half-lives or  days prior to starting study drug) or replaced by safe alternative medication\r\n* Inability to determine the QT interval on screening (corrected QT interval [QTcF], using Fridericias correction)\r\n* Systolic blood pressure (SBP) >  mmHg or <  mmHg at screening\r\n* Bradycardia (heart rate <  at rest), by electrocardiogram (ECG) or pulse, at screening\r\n* Tachycardia (heart rate >  at rest), by ECG or pulse at screening
Clinically significant cardiac abnormalities including QRS duration of > msec; QTcF > msec for women and > msec for men; Abnormal cardiac rhythm; Clinically significant cardiac valve abnormality; Documented history of left ventricular ejection fraction <. within  months; Permanent pacemaker or automatic implantable cardioverter defibrillator; History of torsades de pointes, congenital long QT syndrome, or family history of long QT syndrome or sudden death
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, known serious cardiac illness or psychiatric illness/social situations that would limit compliance with study requirements; known serious cardiac illness or medical conditions include, but are not limited to:\r\n* History of documented congestive heart failure (CHF), New York Heart Association (NYHA) class II/III/IV, with a history of dyspnea, orthopnea, or edema that requires current treatment with angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, beta blockers, or diuretics\r\n** NOTE: use of these medications for the treatment of hypertension is allowed\r\n* Screening QTc (QT interval corrected for heart rate) >  msec or history of QT (cardiac interval from start of Q wave to end of T wave) prolongation while taking other medications\r\n* High-risk uncontrolled arrhythmias (ventricular arrhythmias, high-grade atrioventricular [AV]-block, supra-ventricular arrhythmias that are not adequately rate-controlled)\r\n* Arrhythmias that require current treatment with the following anti-arrhythmic drugs: flecainide, moricizine, or propafenone\r\n* Current coronary artery disease with a history of myocardial infarction, angioplasty, or coronary bypass surgery within the preceding  months, or angina pectoris that has been symptomatic within the preceding  months
Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia.
Patient has impaired cardiac function including any of the following: \r\n* Presence or history of pericardial effusion and/or pericarditis\r\n* Acute myocardial infarction, symptomatic angina pectoris =<  months prior to starting study drug \r\n* Presence of congestive heart failure >= New York Heart Association (NYHA) class \r\n* Corrected QT interval (QTc) >  ms on a screening electrocardiogram (ECG) \r\n* Screening left ventricular ejection fraction (LVEF) < % by echocardiography or multi gated acquisition scan (MUGA) \r\n* Uncontrolled cardiac arrhythmia including uncontrolled atrial fibrillation/atrial flutter/sinus tachycardia, complete left bundle branch block, congenital long QT syndrome\r\n* Presence of permanent cardiac pacemaker \r\n* Other clinically significant heart disease
Impaired cardiac function:\r\n* Corrected QT interval (QTc) >  on screening electrocardiogram (ECG)\r\n* Previous history of angina pectoris or acute myocardial infarction (MI) within  months\r\n* Congestive heart failure (New York Heart Association functional classification III-IV) or baseline multigated acquisition scan (MUGA)/echocardiogram (ECHO) shows estimated left ventricular ejection fraction (LVEF) < %\r\n* Any history of torsade de pointes, ventricular fibrillation, uncontrolled ventricular tachycardia, or uncontrolled atrial fibrillation
Clinically significant, uncontrolled heart disease and/or recent events including any of the following:\r\n* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within  months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Patient has a left ventricular ejection fraction (LVEF) < % as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening\r\n* History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within  months of screening\r\n* Congenital long QT syndrome or family history of long QT syndrome\r\n* Bradycardia (heart rate < at rest), by electrocardiography (ECG) or pulse, at screening\r\n* Systolic blood pressure (SBP) > mmHg or < mmHg at screening
Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following: a. History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within  months prior to screening. b. History of documented congestive heart failure (New York Heart Association functional classification III-IV). c. Documented cardiomyopathy. d. Left ventricular ejection fraction (LVEF) < % as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening. e. Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block). Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: a. Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia. b. Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within  half-lives or  days prior to starting study drug) or replaced by safe alternative medication. c. Inability to determine the QT interval on screening (QTcF, using Fridericias correction). d. Systolic blood pressure (SBP) >  mmHg or <  mmHg at screening.
Impaired cardiac function including any of the following:\r\n* Inability to monitor the QT interval on electrocardiogram (ECG)\r\n* Congenital long QT syndrome or a known family history of long QT syndrome\r\n* Clinically significant resting brachycardia (<  beats per minute)\r\n* Corrected QT (QTc) >  msec on baseline ECG; NOTE: if the ECG shows a QTc interval greater than  msecs at screening triplicates should be performed, one minute apart to confirm the finding (after replacement of any electrolyte imbalance); if / or / of the ECGs confirm the QT prolongation (i.e. QTc interval >  msecs) the patient must not be included into the trial\r\n* Myocardial infarction =<  months prior to starting study\r\n* Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension) \r\n* History of or presence of clinically significant ventricular, atrial tachyarrhythmias or ejection fraction cutoff\r\n* Left ventricle ejection fraction < %\r\n* History of congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
Impaired cardiac function or clinically significant cardiac diseases, including any of the following: a) history of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis less than  months prior to screening b) history of documented congestive heart failure (New York Heart Association functional classification III-IV) c) documented cardiomyopathy d) patient has a left ventricular ejection fraction (LVEF) less than % as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening e) history of ventricular, supraventricular, nodal arrhythmias, or any other cardiac arrhythmias, long QT syndrome or conduction abnormality within  months prior to starting study drug f) congenital long QT syndrome or a family history of corrected QT interval (QTc) prolongation g) on screening, inability to determine the corrected QT for Fridericia (QTcF) interval on the electrocardiogram (ECG) (i.e.: unreadable or not interpretable) or QTcF >  msec (using Fridericias correction); all as determined by screening ECG (mean of triplicate ECGs)
Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia
Clinically significant cardiac disease or impaired cardiac function such as: \r\n* Congestive heart failure (CHF) requiring treatment (New York Heart Association >= grade ), left ventricular ejection fraction (LVEF) =< % dose determined by multi-gated acquisition (MUGA) scan or echocardiogram, or uncontrolled arterial hypertension defined by blood pressure greater than / mmHg at rest (average of  consecutive readings) \r\n* History or current evidence of clinically significant cardiac arrhythmias, atrial fibrillation and/or conduction abnormality, (e.g. congenital long QT syndrome, high grade/complete atrioventricular [AV] blockage)\r\n* Acute coronary syndrome (including myocardial infarction, unstable angina, coronary artery bypass graft [CABG], for coronary angiography angioplasty and stenting), <  months prior to screening\r\n* QT interval adjusted according to Fridericia (QTcF) >  msec on screening electrocardiogram (EKG)
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 registration\r\n* Congestive heart failure within  months prior to registration, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards within  months prior to registration\r\n* History of clinically significant (as determined by the treating physician) atrial arrhythmia\r\n* Any history of ventricular arrhythmia\r\n* Active venous thromboembolism including deep venous thrombosis or pulmonary embolism that is not amenable to treatment with anticoagulants\r\n* Patients with congenital prolonged QT syndromes and abnormal baseline prolonged corrected QT (QTc) (>  ms in men and >  ms in women)\r\n* Patients with an ejection fraction =< % as assessed by a baseline echocardiogram
Patients with clinically significant cardiac disease or impaired cardiac function are not eligible for participation; this includes patients with:\r\n* Congestive heart failure (CHF) requiring treatment (New York Heart Association [NYHA] grade >= )\r\n* Left ventricular ejection fraction (LVEF) < % as determined by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* Uncontrolled arterial hypertension defined by blood pressure > / mm Hg at rest (average of  consecutive readings)\r\n* History or current evidence of unstable, clinically significant cardiac arrhythmias or patients that require medications with a narrow therapeutic window, atrial fibrillation and/or conduction abnormality (e.g. congenital long QT syndrome, high-grade/complete atrioventricular [AV]-blockage)\r\n* Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft [CABG], coronary angioplasty, or stenting), <  months prior to screening\r\n* QTc >  msec on screening
Clinically significant cardiac disease or impaired cardiac function, such as:\r\n* Congestive heart failure requiring treatment (e.g., New York Heart Association class II, III or IV)\r\n* Acute coronary syndromes <  months prior to screening (including myocardial infarction, unstable angina, coronary artery bypass graft, coronary angioplasty, or stenting)\r\n* Uncontrolled arterial hypertension defined by blood pressure > / mm Hg at rest (average of  consecutive readings)\r\n* History or current evidence of unstable, clinically significant cardiac arrhythmias or patients that require medications with a narrow therapeutic window, atrial fibrillation and/or conduction abnormality, e.g. congenital long QT syndrome, high-grade/complete atrioventricular (AV) blockage\r\n* Corrected QT interval (QTc) >  msec on screening electrocardiogram (ECG)
Participants with any of the following cardiac conditions:\r\n* History of long QT syndrome\r\n* Frederica corrected QT interval (QTcF) >=  ms during screening electrocardiogram (ECG)\r\n* History of clinically manifest ischemic heart disease including myocardial infarction, stable or unstable angina pectoris, coronary arteriography or cardiac stress testing/imaging with findings consistent with infarction or clinically significant coronary occlusion =<  months prior to study start\r\n* History of heart failure or left ventricular (LV) dysfunction (left ventricular ejection fraction [LVEF] =< %) by multi gated acquisition scan (MUGA) or echocardiogram (ECHO)\r\n* Clinically significant ECG abnormalities including one or more of the following: left bundle branch block (LBBB), right bundle branch block (RBBB) with left anterior hemiblock (LAHB); ST segment elevations or depressions >  mm, or nd (Mobitz II) or rd degree atrioventricular (AV) block\r\n* History and presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or torsades de pointes\r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with a hypertensive regimen)\r\n* Clinically significant resting bradycardia (<  beats per minute)\r\n* Patients who are currently receiving treatment with any medication which has a relative risk or prolonging the corrected QT (QTc) interval or inducing torsades de pointes and cannot be switched or discontinued to an alternative drug prior to commencing AUY dosing\r\n* Patients who are on a cardiac pacemaker
Participants with following cardiac criteria:\r\n* History of long QT syndrome\r\n* Fridericia corrected QT interval (QTcF) >=  ms during screening electrocardiogram (ECG)\r\n* History of clinically manifest ischemic heart disease including myocardial infarction, stable or unstable angina pectoris, coronary arteriography or cardiac stress testing/imaging with findings consistent with infarction or clinically significant coronary occlusion =<  months prior to study start\r\n* History of heart failure or left ventricular (LV) dysfunction (LV ejection fraction [EF] =< %) by multi gated acquisition scan (MUGA) or echocardiogram (ECHO)\r\n* Clinically significant ECG abnormalities including one or more of the following: left bundle branch block (LBBB), right bundle branch block (RBBB) with left anterior hemiblock (LAHB); ST segment elevations or depressions > mm, or nd (Mobitz II) or rd degree atrioventricular block (AV) block\r\n* History and presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or torsades de pointes\r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with a hypertensive regimen)\r\n* Clinically significant resting bradycardia (<  beats per minute)\r\n* Participants who are currently receiving treatment with any medication which has a relative risk or prolonging the QTcF interval or inducing torsades de pointes (as listed in protocol) and cannot be switched or discontinued to an alternative drug prior to commencing AUY dosing\r\n* Participants who are on a cardiac pacemaker
Significant heart disease defined as:\r\n* Significant coronary arterial disease\r\n** Myocardial infarction in the last  months, angina in the previous  months,\r\n** Troponin elevation at level of myocardial infarction as defined by the manufacturer\r\n** Ischemic changes on electrocardiogram (ECG)\r\n* Atrio-ventricular block greater than st degree, in absence of pacemaker\r\n* Corrected QT interval (QTc) greater than  ms (CTCAE . grade  abnormality is acceptable)\r\n* History of ventricular arrhythmia\r\n* Left ventricular ejection fraction below the institutional limit of normal
Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:\r\n* Left ventricular ejection fraction (LVEF) < % as determined by Multiple Grated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* ST depression or elevation of >= . mm in  or more leads\r\n* Congenital long QT syndrome\r\n* History or presence of ventricular arrhythmias or atrial fibrillation\r\n* Clinically significant resting bradycardia (<  beats per minutes)\r\n* Corrected QT interval (QTc) >  msec on screening electrocardiogram (ECG)\r\n* Complete left bundle branch block\r\n* Right bundle branch block + left anterior hemiblock (bifascicular block)\r\n* Unstable angina pectoris =< months prior to starting study drug\r\n* Acute myocardial infarction =<  months prior to starting study drug\r\n* Other clinically significant heart disease such as congestive heart failure requiring treatment (New York Heart Association [NYHA] class III or IV)
QT related exclusion criteria:\r\n* QT interval corrected using Fridericias formula (QTcF) at screening >  msec\r\n* History of syncope or family history of idiopathic sudden death\r\n* Sustained or clinically significant cardiac arrhythmias\r\n* Risk factors for torsades de pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade atrioventricular (AV) block\r\n* Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), human immunodeficiency virus (HIV), cirrhosis, uncontrolled hypothyroidism or cardiac failure\r\n* Concomitant medication(s) known to increase the QT interval
History of clinically significant cardiac dysfunction, including the following:\r\n* Current unstable angina\r\n* Symptomatic congestive heart failure of New York Heart Association (NYHA) class  or higher \r\n* History of congenital long QT syndrome or mean QT interval using the Fridericia correction formula (QTcF) >  msec at baseline or uncorrectable electrolyte abnormalities\r\n* Uncontrolled hypertension >= grade  (patients with a history hypertension controlled with anti-hypertensives to =< grade  are eligible)\r\n* Patients with left ventricular ejection fraction (LVEF) as measured by echocardiogram or multiple gated acquisition (MUGA) scan below institutional lower limit of normal or below %, whichever is lower, will be excluded from the study\r\n* Uncontrolled arrhythmias\r\n* Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack within the previous  months
Impaired cardiac function including any one of the following: a. inability to monitor the QT interval on electrocardiogram (ECG), b. congenital long QT syndrome or a known family history of long QT syndrome, c. clinically significant resting brachycardia (<  beats per minute), d. QTc >  msec on baseline ECG; if QTc >  msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc, e. impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following: history of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) <  months prior to screening, symptomatic chronic heart failure, history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality <  months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia
Patients with risk factors for torsades de pointes, including uncorrected hypokalemia, uncorrected hypomagnesemia, family history of long QT syndrome, clinically significant/symptomatic bradycardia, high-grade atrio-ventricular (AV) block, autonomic neuropathy (including that caused by diabetes or Parkinsons disease, uncontrolled hypothyroidism, cirrhosis, or the use of concomitant medications known to prolong the QT interval)
Uncontrolled intercurrent illness including, but not limited to,\r\n* Ongoing or active infection\r\n* Psychiatric illness/social situations that would limit compliance with study requirements\r\n* Clinically significant cardiac disease including any of the following:\r\n** Congestive heart failure requiring treatment (New York Heart Association grade >= ), left ventricular ejection fraction (LVEF) < % as determined by multi gated acquisition scan (MUGA) scan or echocardiogram\r\n** Uncontrolled hypertension (defined as systolic blood pressure [BP] >=  mmHg OR diastolic BP >=  mmHg despite maximal anti-hypertensive medications: refer to World Health Organization [WHO]-International Society of Hypertension [ISH] guidelines)\r\n** History or presence of clinically significant ventricular arrhythmias, atrial fibrillation, resting bradycardia, or conduction abnormality\r\n** Unstable angina pectoris or acute myocardial infarction <  months prior to starting study treatment\r\n** Corrected QT using the Fredericia's formula (QTcF) >  msec (males); >  msec (females)\r\n** History of congenital long QT syndrome
Patient has any of the following cardiac abnormalities:\r\n* Symptomatic congestive heart failure\r\n** History of documented congestive heart failure (New York Heart Association functional classification III-IV), documented cardiomyopathy\r\n** Left ventricular ejection fraction (LVEF) < % as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)\r\n* Myocardial infarction =<  months prior to enrollment\r\n* Unstable angina pectoris\r\n* Serious uncontrolled cardiac arrhythmia\r\n* Symptomatic pericarditis\r\n* Corrected QT interval using Fridericia's formula (QTcF) >  msec on the screening electrocardiogram (ECG) (using the QTcF formula)\r\n* Currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug
Significant active cardiovascular or pulmonary disease including:\r\n* Uncontrolled hypertension (i.e., systolic blood pressure >  mmHg, diastolic blood pressure >  mmHg); use of anti-hypertensive agents to control hypertension before cycle  day  is allowed\r\n* Pulmonary hypertension\r\n* Uncontrolled asthma or oxygen (O) saturation < % by arterial blood gas analysis or pulse oximetry on room air\r\n* Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement\r\n* History of arrhythmia requiring an implantable cardiac defibrillator\r\n* Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG) e.g. medically significant (symptomatic) bradycardia, complete left bundle branch block, third degree heart block and second-degree heart block or history of arrhythmia requiring an implantable cardiac defibrillator; or within the last  months before administration of the first dose of drug:\r\n** Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)\r\n** Placement of a pacemaker for control of rhythm\r\n** Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures\r\n** Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures\r\n** New York Heart Association (NYHA) class III or IV heart failure\r\n** Pulmonary embolism\r\n* Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTcF >=  msec (mean value) obtained from  ECGs, using the screening clinic ECG machine derived QTc value, or history of congenital long QT syndrome, or torsades de pointes); any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, 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* Left ventricular ejection fraction (LVEF) by either multigated acquisition (MUGA) or echocardiography (ECHO) less than lower limit of normal
Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality including any of the following:\r\n* History of angina pectoris, symptomatic pericarditis, coronary artery bypass graft (CABG) or myocardial infarction within  months prior to study entry\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < % as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) detected during screening\r\n* History of cardiac failure, significant/symptomatic bradycardia, long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome or any of the following:\r\n** Known risk to prolong the QT interval or induce torsades de pointes\r\n** Uncorrected hypomagnesemia or hypokalemia\r\n** Systolic blood pressure (SBP) >  mmHg or <  mmHg\r\n** Bradycardia (heart rate <  at rest), by electrocardiogram (ECG) or pulse\r\n** On screening, inability to determine the corrected QT using Fridericia's formula (QTcF) interval on the ECG (i.e.: unreadable or not interpretable) or QTcF >  screening ECG (based on a mean of  ECGs)
Any one of the following currently or in the previous  months: myocardial infarction, congenital long QT syndrome, torsades de pointes, uncontrolled arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), right bundle branch block and left anterior fascicular hemiblock (bifascicular block), unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (congestive heart failure [CHF] New York [NY] Heart Association classification III or IV) , cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism not adequate medically managed with anticoagulants, ongoing cardiac dysrhythmias of CTCAE grade >= , symptomatic atrial fibrillation of any grade, corrected QT (QTc) interval >=  msec at screening