Mean QT interval corrected for heart rate (QTc) >= 470 ms calculated from electrocardiograms (ECGs) using Fridericia’s correction; abnormal ECGs should be repeatedXx_NEWLINE_xXCorrected QT (by Bazett's formula [QTcB]) interval < 450 msecXx_NEWLINE_xXHistory of congenital long QT syndrome or corrected QT interval (QTc) > 450 msec within 2 weeks of randomizationXx_NEWLINE_xXPatients with a history of congestive heart failure (CHF) or are at risk because of underlying cardiovascular disease or exposure to cardiotoxic drugs must have adequate cardiac function as clinically indicated:\r\n* Corrected QT interval (QTC) =< 480 msec\r\n* Shortening fraction of >= 27% by echocardiogram or ejection fraction of >= 50% by gated radionuclide studyXx_NEWLINE_xXParticipants may not have corrected QT (QTc) > 470 msec or family history of long QT syndromeXx_NEWLINE_xXHistory of non-pharmacologically induced prolonged QTc intervalXx_NEWLINE_xXCorrected QT (QTc) =< 480 msec\r\n* Note: Patients should avoid concomitant medication known or suspected to prolong QTc interval or cause Torsades De Pointes; If possible, alternative agents should be considered\r\n* Patients who are receiving drugs that prolong the QTc are eligible if the drug is necessary and no alternatives are availableXx_NEWLINE_xXPatients with QTc interval > 470 millisecondsXx_NEWLINE_xXA resting electrocardiogram (EKG) with a corrected QT (QTC) >= 470 msec detected on 2 or more time points within a 2 hour period or family history of long QT syndrome; if the EKG demonstrates QTC >= 470 msec, the patient will only be eligible if a repeat EKG demonstrates QTC =< 470 msecXx_NEWLINE_xXCorrect QT interval (QTc) =< 480 msec; Note: Patients should avoid concomitant medication known or suspected to prolong QTc interval or cause torsades de pointes; if possible, alternative agents should be considered; patients who are receiving drugs that prolong the QTc are eligible if the drug is necessary and no alternatives are availableXx_NEWLINE_xXProlonged rate corrected QT (QTc) interval < 500 msecXx_NEWLINE_xXPatients with baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes)Xx_NEWLINE_xXPatients must have an electrocardiogram (ECG) within 8 weeks prior to registration to screening step and must meet the following cardiac criteria:\r\n* Resting corrected QT interval (QTc) =< 480 msec\r\n** NOTE: If the first recorded QTc exceeds 480 msec, two additional, consecutive ECGs are required and must result in a mean resting QTc =< 480 msec; it is recommended that there are 10-minute (+/- 5 minutes) breaks between the ECGs\r\n* The following only need to be assessed if the mean QTc > 480 msec\r\n** Check potassium and magnesium serum levels\r\n** Correct any identified hypokalemia and/or hypomagnesemia and may repeat ECG to confirm exclusion of patient due to QTc\r\n** For patients with heart rate (HR) 60-100 beats per minute (bpm), no manual read of QTc is required\r\n** For patients with baseline HR < 60 or > 100 bpm, manual read of QT by trained personnel is required, with Fridericia correction applied to determine QTc\r\n** Patient must not have hypokalemia (value < institutional lower limit of normal)\r\n* No factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval\r\n** NOTE: Patient must be taken off prohibited medication prior to registration to the screening step (Step 0, 2, 4, 6) and remain off these medications thereafter, unless permitted on a subprotocol for the management of treatment related toxicity; patient must be off the drug for at least 5 half-lives prior to registration to the treatment step (Step 1, 3, 5, 7); the medication half-life can be found in the package insert for Food and Drug Administration (FDA) approved drugsXx_NEWLINE_xXPatients must have corrected QT (QTc) =< 480 msec by electrocardiogram (ECG) (corrected using the Bazett’s formula) within 28 days prior to registrationXx_NEWLINE_xXPatients must have corrected QT interval calculated by the Fridericia formula (QTcF) =< 500 ms within 28 days before registrationXx_NEWLINE_xXPatients must have corrected QT (QTc) interval < 500/msec (by Bazett’s formula) on baseline ECGXx_NEWLINE_xXResting electrocardiogram (ECG) with corrected QT (QTc) > 470 msec detected on 2 or more time points within a 24 hour period or family history of long QT syndrome; if ECG demonstrates QTc > 470 msec, patient will be eligible only if repeat ECG demonstrates QTc =< 470 msecXx_NEWLINE_xXCorrected QT interval (QTc) < 480 msecXx_NEWLINE_xXCorrected QT interval (QTc) < 470 milliseconds (msec) on a 12-lead electrocardiogram (ECG) =< 28 days before registrationXx_NEWLINE_xXParticipants may not have any of the following cardiac criteria:\r\n* Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 electrocardiograms (ECGs) using the screening clinic ECG machine-derived QTc value\r\n* No history of QT prolongation associated with other medications that required discontinuation of that medication\r\n* Patient must not be receiving any concomitant medications that are known to be associated with Torsades de Pointes\r\n* Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG eg, complete left bundle branch block, third degree heart block, second degree heart block, any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval\r\n* Symptomatic heart failure – New York Heart Association (NYHA) grade II-IVXx_NEWLINE_xXPatients with a pre-existing diagnosis of a prolonged QT syndrome (even if corrected QT interval [QTc] is normal at the time of APL diagnosis) are excludedXx_NEWLINE_xXPatients with a baseline QTc of > 450 msec are excluded; Bazett’s formula is to be used for measurement of the corrected QT interval: the QT interval (msec) divided by the square root of the RR interval (msec)Xx_NEWLINE_xXCorrected QT interval, QTc < 480 msec\r\n* Note: Repeat echocardiogram is not required if echocardiogram was obtained within 21 days of study enrollmentXx_NEWLINE_xXQTc =< 480 msec; Note: Patients with grade 1 prolonged QTc (450- 480 msec) at the time of study enrollment should have correctable causes of prolonged QTc addressed if possible (i.e., electrolytes, medications)Xx_NEWLINE_xXCorrected QT (QTc) interval =< 480 millisecondsXx_NEWLINE_xXCorrected QT (QTc) interval =< 480 milliseconds; Note: Patients should avoid concomitant medication known or suspected to prolong QTc interval or cause Torsades De Pointes; if possible, alternative agents should be considered; patients who are receiving drugs that prolong the QTc are eligible if the drug is necessary and no alternatives are availableXx_NEWLINE_xXCorrected QT (QTc) interval =< 480 millisecondsXx_NEWLINE_xXResting electrocardiogram (ECG) with corrected QT (QTc) > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndromeXx_NEWLINE_xXPatient 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 12 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) < 50% 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 12 months prior to treatment start\r\n* Family history of corrected QT interval (QTc) prolongation or of unexplainable sudden death at < 50 years of age\r\n* On screening 12 lead electrocardiogram (ECG), any of the following cardiac parameters: bradycardia (heart rate < 50 at rest), tachycardia (heart rate > 90 at rest), PR interval > 220 msec, QRS interval > 109 msec, or Fridericia corrected QT (QTcF) > 450 msec; congenital long QT syndrome or family history of long QT syndrome\r\n* Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg\r\n* Bradycardia (heart rate < 50 at rest), by ECG or pulse, at screeningXx_NEWLINE_xXOn screening, inability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF > 450 msec (using Fridericia’s correction); all as determined by screening ECG (mean of triplicate ECGs)Xx_NEWLINE_xXMarked baseline prolongation of QT/corrected QT (QTc) interval (e.g. demonstration of a QTc interval greater than 500 milliseconds)Xx_NEWLINE_xXProlongation of QTc interval to greater than 480 msecXx_NEWLINE_xXSignificant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, bradycardia, or corrected QT interval (Fridericia’s correction; QTcF) > 470 msecXx_NEWLINE_xXCongenital long QT syndrome or corrected QT interval (QTc) > 500 msecXx_NEWLINE_xXThe subject has a baseline corrected QT interval =< 480 msXx_NEWLINE_xXCorrected QT interval (QTc) on electrocardiogram (EKG) > 480 msecXx_NEWLINE_xXPatients must not have a history of clinically significant arrhythmia, prolonged corrected QT (QTc) interval, or unexplained syncope not thought to be vasovagal in nature within 6 months prior to registrationXx_NEWLINE_xXPatients must not have a screening corrected QT using Fridericia's formula (QTcF) interval > 500 milliseconds (by Fridericia calculation) based on the average of triplicate electrocardiogram (EKG) performed within 7 days prior to registration; note that triplicate EKG is required at other time pointsXx_NEWLINE_xXPatients with a corrected QT interval (QTc) > 480 msecs are NOT eligible for participationXx_NEWLINE_xXCorrected QT interval (QTc) > 480 msecs using Bazett’s formulaXx_NEWLINE_xXScreening electrocardiogram (ECG) with a corrected QT interval (QTc) > 450 msecXx_NEWLINE_xXQT interval corrected through use of Fridericia's formula (QTcF) > 470 millisecondsXx_NEWLINE_xXProlonged Fridericia's corrected QT interval (QTcF) > 450 ms for men and > 470 ms for women at Screening.Xx_NEWLINE_xXResting electrocardiography (EKG) with corrected QT (QTc) > 470 msec or family history of long QT syndrome; if EKG demonstrates QTc > 470 msec, patient will be eligible only if repeat EKG demonstrates QTc ? 470 msecXx_NEWLINE_xXFridericiaís corrected QT interval (QTcF) >/= 480Xx_NEWLINE_xXCorrected QT interval (QTc) > 480 msecs using Bazett’s formulaXx_NEWLINE_xXOngoing cardiac dysrhythmias of NCI CTCAE v4.03 Grade 2 or prolongation of the QTcF interval to >480 msec.Xx_NEWLINE_xXAny of the following cardiac criteria:\r\n* Resting corrected QT interval (QTc) > 480 msec obtained from electrocardiogram (ECG)\r\n* Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG) eg, complete left bundle branch block, third degree heart block\r\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval\r\n* Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association (NYHA) grade >= 2\r\n* Uncontrolled hypotension – systolic blood pressure (BP) < 90 mmHg and/or diastolic BP < 50 mmHg\r\n* Left ventricular ejection fraction (LVEF) below lower limit of normal for siteXx_NEWLINE_xXFamily history of long QT syndrome, with a QTc interval greater than (>) 480 millisecond (msec) at screening, or taking concurrent medications known to prolong QT/QTc intervalXx_NEWLINE_xXBaseline corrected QT interval (QTc) =< 450 msec\r\n* Note: QT interval calculation by the Fridericia formula is permittedXx_NEWLINE_xXProlonged corrected QT (QTc) interval > 500 msec, calculated according to Fridericia's formulaXx_NEWLINE_xXStandard 12-lead electrocardiography (ECG) with the following parameters at screening (defined as the mean of the triplicate ECGs):\r\n* Fridericia's correction formula (QTcF) interval at screening < 450 msec (using Fridericia’ s correction)\r\n* Resting heart rate 50 to 100 beats per minuteXx_NEWLINE_xXPatients with a prolonged corrected QT interval (QTc) interval (>= 450 ms)Xx_NEWLINE_xXSubjects showing an average QTc interval over 3 consecutive electrocardiograms (ECG) >450 msec in males and >470 msec in females at screening (? 480 msec for subjects with bundle branch block (BBB) are not eligible.Xx_NEWLINE_xX12-lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of ? 470 msec Fridericia Formula.Xx_NEWLINE_xXCorrected QT interval (QTc) < 480 msecXx_NEWLINE_xXBaseline QTc exceeding 450 msec (using the Bazett's formula) and/or patients receiving class 1A or class III antiarrythmic agents.Xx_NEWLINE_xXHistory of prolonged QTc interval.Xx_NEWLINE_xXCorrected QT interval (QTc) > 480 msec; history of QT syndrome, Brugada syndrome or known history of QTc prolongation, or torsade de pointesXx_NEWLINE_xXCurrent use of drugs that are known to prolong QT intervalXx_NEWLINE_xXSymptomatic arrhythmia. If QTc greater than or equal to 470ms, confirmation of eligible QTc requires mean calculation from 2 additional electrocardiograms (ECGs) 2?5 minutes apart using Fridericia's Correction Formula (mean less than 470 ms).Xx_NEWLINE_xXBaseline corrected QT (QTc) < 480 msXx_NEWLINE_xXCurrent use of drugs that are known to prolong the QT intervalXx_NEWLINE_xXQTc > 480 msec (based on the mean value of the triplicate electrocardiography [ECG]s), family or personal history of long or short QTc prolongation, or torsade de pointes (Tdp)Xx_NEWLINE_xXBaseline corrected QT (QTc) =< 500 msXx_NEWLINE_xXSubject has a mean QT interval corrected for heart rate using Bazett's (QTcB) or Fridericia's (QTcF) correction ? 500 ms calculated from 3 consecutive 12-lead ECGs at Screening;Xx_NEWLINE_xXEvery effort must be made to avoid the use of a concomitant medication that can prolong the corrected QT (QTc) interval while receiving selumetinib (hyd-sulfate AZD6244); if the patient cannot discontinue medications that prolong QTc interval while receiving selumetinib, close cardiac monitoring should be performedXx_NEWLINE_xXRate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead electrocardiography (ECG) during screeningXx_NEWLINE_xXPatients must have at screening a standard 12-lead electrocardiogram (ECG) with mean values that meet the following parameters:\r\n* Fridericia's correction QT (QtcF) interval at screening < 450 msec (using Fridericia’s correction)\r\n* Resting heart rate of 50-90 beats per minute (bpm)Xx_NEWLINE_xXAdequate cardiac conductivity with corrected QT interval (QTC) of < 450 ms on screening electrocardiogram (ECG)Xx_NEWLINE_xXPatients with prior history of QTC prolongation or QTC > 450 ms on screening ECG will be excludedXx_NEWLINE_xXA baseline corrected QT interval of > 500 ms; patients with left bundle branch block that is deemed not clinically significant may be enrolled with corrected QT > 500Xx_NEWLINE_xXBaseline corrected Fridericia QT (QTcF) >= 450 ms (males) or >= 470 ms (females)Xx_NEWLINE_xXPatients with QTc interval > 450 msec.Xx_NEWLINE_xXPatients who are on treatment with drugs known to prolong the QT/QTc interval.Xx_NEWLINE_xXMust not have a family history of long corrected QT interval (QTc) syndromeXx_NEWLINE_xXCorrected QT interval (QTc) using Fridericia's formula (QTcF) value > 480 msec at Screening; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy at Screening; previous history of drug induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on electrocardiogram (ECG).Xx_NEWLINE_xXProlongation of corrected QT [QTcF (Fridericia's corrected QT interval)] interval to greater than 480 msec when electrolytes balance is normalXx_NEWLINE_xXQT duration corrected for heart rate by Fridericia's formula (QTcF) <450 msec or <480 milliseconds (msec) for subjects with bundle branch block.Xx_NEWLINE_xXOn screening inability to determine the corrected QT using Fridericia's formula (QTcF) interval on the ECG (i.e.: unreadable or not interpretable) or QTcF > 450 msec (using Fridericia’s correction); all as determined by screening ECG (mean of triplicate ECGs)Xx_NEWLINE_xXCorrected QT interval (QTc) of < 480 millisecondsXx_NEWLINE_xXCongenital long QT syndrome or a corrected QTc interval ? 470 ms at screeningXx_NEWLINE_xXUnstable cardiac dysrhythmias or persistent prolongation of the corrected QT interval (QTc) (Fridericia) to >450 msec for males or >470 msec for females.Xx_NEWLINE_xXQT interval corrected using Fridericia formula (QTcF) > 500 msec on average of screening electrocardiograms (EKGs) performed within 28 days of first dose of cabozantinib; three EKGs must be performed at screening; if the average of these three consecutive results for QTcF is > 500 msec, the subject is ineligibleXx_NEWLINE_xXPatients with a QT interval > 480 msec (using the Bazett's formula) within 28 days prior to registration are not eligibleXx_NEWLINE_xXCorrected QT interval (QTc) interval greater than 450 msec (males) or greater than 470 msec (females).Xx_NEWLINE_xXPatients must have a corrected QT (QTc) interval of less than 480 msecXx_NEWLINE_xXMales with mean QTcF values of > 450 msec and females with QTcF values of > 470 msec following 3 ECGs conducted 5 minutes apart from each other; patients who are known to have congenital prolonged QT syndromes; or patients who are on medications known to cause prolonged QT intervals on ECG;Xx_NEWLINE_xXProlongation of corrected QT interval by Fridericia's method (QTcF) at rest, where the mean QTcF interval is > 450 milliseconds (ms) for males and > 470 ms for females based on triplicate ECG.Xx_NEWLINE_xXPatients must not have a corrected QT interval (QTc) of > 480 msec using Bazett’s formulaXx_NEWLINE_xXSignificant uncontrolled or active cardiovascular disease, specifically including, but not restricted to:\r\n* History of clinically significant (as determined by the treating physician) atrial arrhythmia; or any ventricular arrhythmia\r\n* History of congenital long QT syndrome\r\n* Abnormal QT corrected for heart rate using Bazett's formula (QTcB) (>= 450 msec in males and >= 470 msec in females)\r\n* Ejection fraction =< 50% as assessed by echocardiogramXx_NEWLINE_xXCorrected QT (QTc) interval > 470 msecXx_NEWLINE_xXCorrected QT interval by Fredericia (QTcF) > 500 msec within 1 month before the first dose of study treatment:\r\n* Three electrocardiograms (ECGs) must be performed for eligibility determination. If the average of these three consecutive results for QTcF is =< 500 msec, the subject meets eligibility in this regardXx_NEWLINE_xXPatients who have ongoing cardiac dysrhythmias, atrial fibrillation, or prolongation of corrected QTc interval to > 480 msec on 2 out of 3 electrocardiograms (EKGs) (if first EKG has QTc < 480, no need to repeat, if first EKG has QTc > 480 repeat twice for a total of 3 EKGs)Xx_NEWLINE_xXConsistent corrected QT (QTc) > 470 msec on more than one screening electrocardiography (ECG). Patients with a history of long QTc syndrome or personal or family history of ventricular arrhythmias will be excluded.Xx_NEWLINE_xXParticipants must have a corrected QT (QTc) of =< 470 msec for females and =< 450 for males on the screening electrocardiogram (EKG)Xx_NEWLINE_xXHave a heart-rate corrected QT interval using Fridericia's method (QTcF) >470 msec.Xx_NEWLINE_xXFridericia-corrected QT interval (QTcF) > 470 msec (female) or history of congenital long QT syndrome.Xx_NEWLINE_xXAny clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiography (ECG), e.g. complete left bundle branch block, third-degree heart block, second-degree heart block, QT interval corrected by Fridericia’s formula (QTcF) of >= 450 ms in males or >= 470 ms in femalesXx_NEWLINE_xXAny factors that increase the risk of corrected QT interval (QTc) prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives, or any concomitant medication known to the prolong the QT interval that a patient is unable to stopXx_NEWLINE_xXCurrent treatment with medications that are well known to prolong the QT intervalXx_NEWLINE_xXHas electrocardiogram with a QT interval corrected for heart rate using Fridericia's formula (QTcF) > 470 msec or ECG with second degree type 2 or third degree atrioventricular block.Xx_NEWLINE_xXPatients with QTc interval >450 msec for male and >470 msec for female.Xx_NEWLINE_xXPatients who are on treatment with drugs known to prolong the QT/QTc interval.Xx_NEWLINE_xXHas ECG abnormalities that make QT interval corrected (QTc) evaluation difficult (e.g., severe morphologic abnormalities).Xx_NEWLINE_xXQTcF > 460 msec on Screening electrocardiogram (ECG)Xx_NEWLINE_xXProlonged Fridericia's corrected QT (QTcF) > 450 ms for men and > 470 ms for women at screening.Xx_NEWLINE_xXFredericia-corrected QT interval (QTcF) >470 msec (female) or >450 msec (male), or history of congenital long QT syndrome.Xx_NEWLINE_xXOn screening, any of the following cardiac parameters: interval between P and R (PR interval) >220 milliseconds (msec), interval between Q, R, and S (QRS) interval >109 msec, or QT interval corrected for heart rate using Fridericia's formula (QTcF) >450 msec;Xx_NEWLINE_xXMedications that have a known risk to prolong the QT interval or induce Torsades de Pointes;Xx_NEWLINE_xXProlongation of QT corrected (QTc) interval to >480 milliseconds (ms)Xx_NEWLINE_xXENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Corrected QT (QTc) =< 480 msecXx_NEWLINE_xXQTc prolongation (defined as a QTc > 450 msecs) or other significant ECG abnormalities including 2nd degree atrioventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats per minute [bpm]). If the screening ECG has a QTc > 450 msecs, the ECG can be submitted for a centralized, cardiologic evaluation.Xx_NEWLINE_xXCorrected QT (QTc) interval < 470 msecXx_NEWLINE_xXBaseline QT interval corrected with Fridericia's method (QTcF) > 480 ms Part 2 Only:Xx_NEWLINE_xXSubjects with corrected QT using Fridericia's formula (QTcF) interval of >= 450 msec if male and >= 470 msec if female; other factors that increase the risk of QT prolongation or arrhythmic events (e.g. heart failure, chronic hypokalemia, family history of long QT interval syndrome) at screening; subjects with bundle branch block should be reviewed by the principal investigator for potential inclusionXx_NEWLINE_xXHistory 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 torsade’s de pointes\r\n* Uncorrected hypomagnesemia or hypokalemia\r\n* Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg\r\n* Bradycardia (heart rate < 50 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 > 450 (based on a mean of 3 ECGs)Xx_NEWLINE_xXParticipants must have a corrected QT (QTc) of =< 470 msec on the screening electrocardiography (EKG)Xx_NEWLINE_xXClinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolonged QT/QTc ([QT interval/corrected QT interval], e.g., a repeated demonstration of a QTc interval > 500 ms)Xx_NEWLINE_xXSubjects with baseline QT prolongation > 470 msecXx_NEWLINE_xXSubjects receiving concomitant medications that prolong corrected QT interval (QTc)Xx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s CorrectionXx_NEWLINE_xXPatient with standard 12-lead electrocardiogram (ECG) with the following parameters at screening (defined as the mean of the triplicate ECGs):\r\n* Fridericia's correction formula (QTcF) interval at screening < 450 msec (using Fridericia’s correction)Xx_NEWLINE_xXConsistent corrected QT (QTc) > 470 msec on more than one screening electrocardiograms (ECGs); patients with a history of long QTc syndrome or personal or family history of ventricular arrhythmias will be excludedXx_NEWLINE_xXClinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolonged QT/ corrected QT (QTc) ([QT interval/corrected QT interval], eg, a repeated demonstration of a QTc interval > 500 ms)Xx_NEWLINE_xXCorrected QT (QTc) interval > 500 msec, unless a bundle branch block is also presentXx_NEWLINE_xXParticipant with mean resting corrected QT interval (specifically QTc calculated using the Fridericia formula [QTcF]) > 450 msec for males and > 470 msec for females, from 3 electrocardiograms (ECGs) performed within 2-5 minutes apart at study entry, or congenital long QT syndromeXx_NEWLINE_xXHistory of congenital long QT syndrome or mean (average of triplicate measurements) corrected QT (QTc) measured using Fridericia's method >/=450 millisecond (ms) at baseline or uncorrectable abnormalities in serum electrolytes (sodium, potassium, calcium, magnesium, phosphorus) VismodegibXx_NEWLINE_xXCorrected QT interval (QTc) =< 480 msecXx_NEWLINE_xXThe participant has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before randomization; note: if initial QTcF is found to be > 500 ms, two additional electrocardiogram (ECGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =< 500 ms, the participant meets eligibility in this regardXx_NEWLINE_xXConsistent corrected QT (QTc) > 450 msec for men and > 470 msec for women by Fridericia formula, on 3 separate electrocardiograms (ECGs)Xx_NEWLINE_xXDocumented within 14 days of registration: Cardiac corrected QT (QTc) interval < 450 msec on electrocardiogram (EKG)Xx_NEWLINE_xXRequired use of a concomitant medication that can prolong the QT intervalXx_NEWLINE_xXProlonged corrected QT (QTc) intervalXx_NEWLINE_xXINCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED BY WASH U GPS LABORATORY): Corrected QT (QTc) interval =< 450 msec for men or =< 470 msec for women within 2 weeks of registrationXx_NEWLINE_xXINCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED AT AN OUTSIDE CLIA CERTIFIED LOCATION): QTc interval =< 450 msec for men or =< 470 msec for women within 2 weeks of registrationXx_NEWLINE_xXMean resting corrected QT (QTc) interval using the Fridericia formula (QTcF) > 450 ms (i.e., grade 1 or higher) for males and > 470 ms for females on electrocardiogram (ECG) prior to initiation of study treatment obtained from 3 electrocardiograms (ECGs) obtained 2-5 minutes apart at study entry, or history of congential long QT syndrome\r\n* If baseline QTc on screening ECG is > 450 ms for males or > 470 ms for females:\r\n** Check potassium and magnesium serum levels\r\n** Correct any identified hypokalemia and/or hypomagnesemia and repeat ECG to confirm QTcF interval\r\n* For patients with baseline heart rate (HR) < 60 bpm or > 100 bpm, manual measurement of QT interval by cardiologist is required, with Fridericia correction applied to that manual measurement to determine the QTc for eligibility consideration\r\n* Note: For patients with HR 60-100 bpm, manual measurement of QTc interval is NOT requiredXx_NEWLINE_xXTreatment with medications that can prolong the QTc interval within the last 2 weeksXx_NEWLINE_xXQTc prolongation >450 ms or other factors that increase the risk for QT interval prolongation (e.g., heart failure, hypokalemia [defined as serum potassium <3.0 mEq/L that is persistent and refractory to correction], family history of long QT interval syndrome, or concomitant use of medications that may prolong QT interval)Xx_NEWLINE_xXParticipant has a Fridericia-corrected QT interval (QTcF) > 450 msec (average of triplicate determinations) per central read.Xx_NEWLINE_xXParticipant has a QTcF interval > 450 msec (average of triplicate determinations) by central read.Xx_NEWLINE_xXBaseline QTc prolongation (e.g., repeated demonstration of QTc interval > 480 milliseconds or history of congenital long QT syndrome or torsades de pointes)Xx_NEWLINE_xXMean resting corrected QT interval (QTc) > 470 msec obtained from 3 electrocardiograms (ECGs), using the Screening clinic ECG machine and Fridericia's formula for QT interval correction.Xx_NEWLINE_xXCorrected QT interval (QTc) < 470 msec (as calculated by the Fridericia correction formula [QTcF]).Xx_NEWLINE_xXUse of drugs that could prolong the QT interval within 7 days before the start of study therapy.Xx_NEWLINE_xXMedical history of uncontrolled but clinically significant abnormal cardiac conduction abnormalities at electrocardiogram (ECG), any history or evidence of long QT syndrome or QTcF interval >450 msec for males and ?470 msec for females (according to Fridericia's correction) at screeningXx_NEWLINE_xXQTc Fridericia (QTcF) >450 msXx_NEWLINE_xXFridericia’s corrected QT (QTcF) value of =< 470 msec on screening electrocardiogram (EKG) within 14 days prior to start of protocol therapy.Xx_NEWLINE_xXECG with correctd QT interval (QTc) >450 msec in males or >470 msec in females at screeningXx_NEWLINE_xXHave a mean QT interval corrected for heart rate (QTc) of ?470 milliseconds on screening electrocardiogram (ECG) as calculated using the Bazett's formula at several consecutive days of assessment.Xx_NEWLINE_xXElectrocardiogram (EKG) documenting corrected QT (QTc) interval < 480 mili (m)second and no clinically significant arrhythmiaXx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from an electrocardiogram (ECG) using Fridericia’s Correction (QTcF)\r\n* At screening, a single ECG will be obtained on which QTcF must be < 470 ms; in case of clinically significant ECG abnormalities, including a QTcF value > 470 ms, 2 additional 12-lead ECGs should be obtained over a brief period (eg, 30 minutes) to confirm the findingXx_NEWLINE_xXMean resting corrected QT interval (QTcF) >470 msec obtained from 3 ECGsXx_NEWLINE_xXHistory or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful. Screening corrected QT (QTc) interval > 470 msec is excluded (corrected by Fridericia). If a single QTc is > 470 milliseconds, the subject may enroll if the average QTc for the 3 ECGs is < 470 milliseconds. For subjects with an intraventricular conduction delay (QRS interval > 120 milliseconds), the JTc interval may be used in place of the QTc with sponsor approval. The JTc must be < 340 milliseconds if JTc is used in place of the QTc. Subjects with left bundle branch block are excluded. Note: QTc prolongation due to pacemaker may enroll if the JTc is normal or with medical monitor approval.Xx_NEWLINE_xXAny medications that are known to prolong the QTc interval.Xx_NEWLINE_xXCorrected QT interval (QTc) using Fridericia's formula (QTcF) value > 480 msec at Screening; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy at Screening; previous history of drug induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on electrocardiogram (ECG).Xx_NEWLINE_xXProlonged baseline QTcXx_NEWLINE_xXCorrected QT Interval (QTc) > 470 milliseconds (msec) on a 12-lead ECG obtained during the screening period\r\n* Note: If a machine reading is above this value, the ECG should be reviewed by a qualified reader and confirmed on a subsequent ECGXx_NEWLINE_xXCorrected QT (QTc) interval < 480 ms (as calculated by the Fridericia correction formula)Xx_NEWLINE_xXSubject has corrected QT (QTc) interval < 500 msec on baseline electrocardiogramXx_NEWLINE_xXLong QT or prolonged QTc (>460 ms)Xx_NEWLINE_xXHistory of long QT syndrome or whose corrected QT(QTc) interval measured (Fridericia method) at screening is prolonged (>450 ms)Xx_NEWLINE_xXFridericia's corrected QT interval (QTcF) =< 450 msecXx_NEWLINE_xXCorrected QT interval at screening greater than (>) 480 milliseconds (ms) (average of triplicate screening measurements)Xx_NEWLINE_xXPatients with corrected QT (QTc) interval of > 450 msec or those on medications known to prolong QTc intervalXx_NEWLINE_xXPatients who have corrected QT (QTc) interval of > 470 msec on a screening electrocardiogramXx_NEWLINE_xXQT interval corrected for rate (QTc) > 450 msec on the electrocardiogram (ECG) obtained at ScreeningXx_NEWLINE_xXQTc interval calculated according to Fridericia's formula (QTcF = QT/RR0.33; RR = RR interval) of ? 450 msec on screening electrocardiogram (ECG).Xx_NEWLINE_xXPatients with prolonged corrected QT (QTc) interval (> 450 msec) (for cohort 2a and 2b [belinostat cohorts] only, electrocardiogram [ECG] nor required for cohort 1)Xx_NEWLINE_xXAny known cardiac abnormalities such as:\r\n* Congenital long QT syndrome\r\n* Corrected QT(QTc) interval >= 500 millisecondsXx_NEWLINE_xXElectrocardiogram (ECG) abnormalities of Q-wave infarction, unless identified 6 or more months prior to screening or QTc Fridericia (F) interval >460 msecXx_NEWLINE_xXBaseline corrected QT (QTc) interval >= 480 millisecondsXx_NEWLINE_xXCorrected QT (QTc) interval (using Fridericia’s correction formula, QTcF, if prolonged) > 470 msecXx_NEWLINE_xXMedications with a known risk of prolongation of QT intervalXx_NEWLINE_xXElectrocardiogram (ECG) corrected QT (QTC) < 450 msecXx_NEWLINE_xXHave QT corrected interval of >450 milliseconds (msec) on screening electrocardiogram (ECG)Xx_NEWLINE_xXBaseline electrocardiogram (EKG) with corrected QT interval (QTc) > 470 msec (including subjects on medication); subjects with ventricular pacemaker for whom QT interval is not measurable will be eligible on a case-by-case basisXx_NEWLINE_xXPatients must have a baseline electrocardiogram (ECG) with QT interval corrected by Fridericia's formula (QTcF) within the normal range within 28 days prior to registrationXx_NEWLINE_xXNo previous history of corrected QT (QTc) prolongation as a result of medication that required discontinuation of that medicationXx_NEWLINE_xXNo QTc with Bazett’s correction that is unmeasurable, or >= 480 msec on screening electrocardiogram (ECG) obtained within 7 days prior to registration for protocol therapy; if a subject has QTc >= 480 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart); the average QTc from the three screening ECGs must be < 480 msec in order for the subject to be eligible for the study; NOTE: co-administration of drugs that in some reports might be associated with Torsades de Pointes but at this time lack substantial evidence of Torsades de Pointes should be avoided within 2 weeks of randomization and during study; however, these drugs will be allowed, at the discretion of the investigator, if considered\r\nabsolutely necessary; in such cases, the subject must be closely monitored including regular checks of QTc and electrolytes; for patients who start on the drugs in this group while on the study treatment, the ECG must be checked within 24 hours of commencing the concomitant medication and then at least once per week while the patient remains on the medication; the frequency of ECG monitoring could revert to the standard schedule if no QTc prolongation has been noted during 4 weeks of co-administration of a drug; the electrolytes should be maintained within the normal range using supplements if necessaryXx_NEWLINE_xXResting electrocardiogram (ECG) with corrected QT interval by Fridericia (QTcF) > 470 msec or family history of long QT syndromeXx_NEWLINE_xXSubjects with prolonged corrected QT (QTc) (> 450 msec) will be excluded from the study.Xx_NEWLINE_xXCorrected QT interval using Fridericia’s formula value > 480 msec at screening; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy at screening; previous history of drug-induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on electrocardiogram (ECG)Xx_NEWLINE_xXCorrected QT (QTc) interval ? 470 msec on screening electrocardiogram (ECG)Xx_NEWLINE_xXResting electrocardiogram (ECG) with corrected QT interval (QTc) > 470 msec on 2 or more time points within a 24-hour period or family history of long QT syndromeXx_NEWLINE_xXHas a mean QT interval corrected for heart rate (QTc) ? 470ms calculated from 3 electrocardiograms (ECGs) using Fredericia’s CorrectionXx_NEWLINE_xXCorrected QT (QTc) interval (i.e., Friderica’s correction [QTcF]) >= 450 ms 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) at screeningXx_NEWLINE_xXSubject has QT interval corrected (QTc) >480 ms (both males and females) at Screening (repeat values may be obtained during the period between Screening and admission to the study site).Xx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms using Fridericia’s correction.Xx_NEWLINE_xX12-lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of ? 470 msecXx_NEWLINE_xXCorrected QT (QTc) interval using Fridericia’s formula (QTcF) >= 450 msec. Bundle branch block and prolonged QTc interval are permitted after discussion with the PI.Xx_NEWLINE_xXPatients who have a QT interval corrected using Fridericia's formula (QTcF) of > 450 msec.Xx_NEWLINE_xXOngoing cardiac dysrhythmias of National Cancer Institute (NCI) CTCAE grade >= 2 or prolongation of the corrected QT interval (QTc) interval to > 500 msecXx_NEWLINE_xXHistory or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful; screening corrected QT (QTc) interval > 470 milliseconds is excluded; in the event that a single QTc is > 470 milliseconds, the subject may enroll if the average QTc for the 3 ECGs is < 470 milliseconds; for subjects with an intraventricular conduction delay (QRS interval > 120 milliseconds), the corrected JT (JTc) interval may be used in place of the QTc with sponsor approval; the JTc must be < 340 milliseconds if JTc is used in place of the QTc; subjects with left bundle branch block are excluded\r\n* Note: QTc prolongation due to pacemaker may enroll if the JTc is normalXx_NEWLINE_xXCorrected QT interval (QTc) prolongation (defined as a QTc >450 ms for males and >470 ms for females [Fridericia's correction]) or other clinically significant electrocardiogram (ECG) abnormalities as assessed by the investigatorXx_NEWLINE_xXSubjects must have a 12-lead electrocardiogram (EKG) showing no active ischemia and Fridericia's corrected QT interval (QTcF) less than 480 ms.Xx_NEWLINE_xXResting electrocardiogram (ECG) with corrected QT (QTc) > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.Xx_NEWLINE_xXCRITERIA SPECIFIC FOR COHORT #2 (MCL): Significant screening electrocardiogram (ECG) abnormalities including, but not limited to, left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) >= 470 msec; subjects with a cardiac pacemaker who have a QTc interval of >= 470msec may be eligible if these findings are considered not clinically significant as documented via a cardiology evaluationXx_NEWLINE_xXHave normal QT interval on electrocardiogram (ECG) evaluation QT corrected of =< 450 ms in males or =< 470 ms in females obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine-derived corrected QT (QTc) valueXx_NEWLINE_xXParticipants with any history of corrected QT (QTc) prolongation (i.e. QTc interval of > 450 msec)Xx_NEWLINE_xXSTRATUM A: Participants with QTc interval of > 450 msec on screening electrocardiogram (ECG)Xx_NEWLINE_xXSTRATUM B: Participants with QTc interval of > 450 msec on screening ECGXx_NEWLINE_xXSTRATUM C: Participants with QTc interval of > 450 msec on screening ECGXx_NEWLINE_xXAny of the following cardiac abnormalities or history:\r\n* Mean resting corrected QT interval (QTc) > 470 msec, obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value\r\n* Any clinically important 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 heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT intervalXx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s Correction.Xx_NEWLINE_xXUse of a drug known to prolong the cardiac QT interval.Xx_NEWLINE_xXQTcF <500 msecXx_NEWLINE_xXMean resting corrected QT interval (QTc) calculated using Fridericia's formula (QTcF) of >450 msec for males and >470 msec for females obtained from 3 electrocardiograms (ECGs) taken over 5 minutesXx_NEWLINE_xXMean QT interval ? 470 msecXx_NEWLINE_xXPatients taking medications that have the potential to prolong the QT intervalXx_NEWLINE_xXHistory or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful; screening corrected QT (QTc) interval >= 480 milliseconds is excluded; in the event that a single QTc is >= 480 milliseconds, the subject may enroll if the average QTc for the 3 ECGs is < 480 milliseconds; for subjects with an intraventricular conduction delay (QRS interval > 120 milliseconds), the corrected JT (JTc) interval may be used in place of the QTc with the approval of the principal investigator; the JTc must be < 340 milliseconds if JTc is used in place of the QTc; subjects with left bundle branch block are excluded; note: QTc prolongation due to pacemaker may enroll if the JTc is normalXx_NEWLINE_xXQT interval with Fridericia's correction [QTcF] >470 milliseconds. The QTcF should be calculated as the arithmetic mean of the QTcF on triplicate ECGs. In the case of potentially correctible causes of QT prolongation (e.g., medications, hypokalemia), the triplicate ECG may be repeated once during screening and that result may be used to determine eligibility.Xx_NEWLINE_xXPlanned concomitant use of medications known to prolong the QT/QTc intervalXx_NEWLINE_xXProlongation of corrected QT using Fridericia's formula (QTcF) interval to > 480 msXx_NEWLINE_xXElectrocardiogram (ECG) without evidence of clinically significant ventricular arrhythmias or ischemia as determined by the investigator and a rate-corrected QT interval (QTc, Bazett's formula) of < 480 msecXx_NEWLINE_xXAny of the following cardiac criteria: \r\n* Mean resting corrected QT interval (QTc using Fridericia's formula) > 470 msec;\r\n* Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG) e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250msec;\r\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT intervalXx_NEWLINE_xXCOHORT 1: HORMONE RECEPTOR POSITIVE BREAST CANCER: Patients with a mean Fridericia's correction formula (QTcF) interval of > 500 msec or receiving therapeutic agents known to prolong the QT intervalXx_NEWLINE_xXCOHORT 2: TRIPLE NEGATIVE BREAST CANCER: Patients with a mean QTcF interval of > 500 msec or receiving therapeutic agents known to prolong the QT intervalXx_NEWLINE_xXCOHORT 3: ENDOMETRIAL CANCER: Patients with a mean corrected QT (QTc) interval of > 500 msec or receiving therapeutic agents known to prolong the QT intervalXx_NEWLINE_xXCorrected QT (QTc) < 500 msec by FridericiaXx_NEWLINE_xXProlonged rate corrected QT (QTc) interval ? 500 msec, calculated according to institutional guidelinesXx_NEWLINE_xXResting ECG with corrected QT (QTc) > 470 msec on two or more time points within a 24 hour period, noted within 14 days of treatment, or family history of long QT syndromeXx_NEWLINE_xXPatients with a known history of corrected QT (QTc) prolongation (> 480 msec), or known history of ventricular tachycardia, ventricular fibrillation or Torsades de pointes are not eligibleXx_NEWLINE_xXQTc interval using Fridericia's formula (QTcF) ?450 msec or other factors that increase the risk of QT interval prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome). Bundle branch block and prolonged QTc are permitted with approval of the study SponsorXx_NEWLINE_xXTaking medications that are known to prolong the QT interval unless they can be transferred to other medications within ?5 half-lives prior to dosing (If equivalent medication is not available QTc will be closely monitored)Xx_NEWLINE_xXCorrected QT interval (QTc) prolongation > 480 msecXx_NEWLINE_xXAny of the following cardiac criteria:\r\n* Mean resting corrected QT interval (QTc using Frederica’s formula [QTcF]) > 470 msec\r\n* Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG) (e.g., complete left bundle branch block, third degree heart block, second degree heart block)\r\n* Congenital long QT syndrome or family history of long QT syndromeXx_NEWLINE_xXBaseline prolongation of the rate-corrected QT interval (QTc) > 480 milliseconds or history of congenital long QT syndrome or Torsades de pointesXx_NEWLINE_xXWithin two weeks prior to enrollment: Corrected QT (QTc) interval =< 450 msXx_NEWLINE_xXCorrected QT (QTc) interval =< 450 msecsXx_NEWLINE_xXRequired use of a concomitant medication that can prolong the QT intervalXx_NEWLINE_xXSubjects with a corrected QT (QTc) > 480 ms (QTc > 510 msec for subjects with a bundle branch block at baselineXx_NEWLINE_xXQT corrected by Bazzett's formula (QTcB) must be < 470 milliseconds (ms) for males and < 480 ms for femalesXx_NEWLINE_xXQT interval corrected for heart rate using Fridericia's formula (QTcF) =< 500 msecXx_NEWLINE_xXA corrected QT interval calculated by the Fridericia formula (QTcF) > 500 milliseconds within 28 days before first dose of study treatment. Three electrocardiograms (ECGs) must be performed for eligibility determination. If the average of these three consecutive results for QTcF is =< 500 milliseconds, the subject will be eligible.Xx_NEWLINE_xXBaseline Fridericia's corrected QT (QTcF) interval greater than 470 msec (female) or greater than 450 msec (male), history of congenital long QT syndrome, the presence in the screening electrocardiography (ECG) of a conduction abnormality that in the opinion of the investigator would preclude safe participation in this studyXx_NEWLINE_xXConcomitant use of a drug with a known risk of corrected QT interval (QTc) prolongationXx_NEWLINE_xXBaseline electrocardiogram (EKG) with corrected QT (QTc) > 470 msec (including subjects on medication); subjects with ventricular pacemaker for whom QT interval is not measurable will be eligible on a case-by-case basis at medical doctor (MD) discretionXx_NEWLINE_xXProlonged rate corrected QT (QTc) interval >= 500 msec, calculated according to institutional guidelinesXx_NEWLINE_xXCorrected QT interval (QTc) > 500 ms, uncorrectable by managing electrolytes and medications, using the Fridericia's correction (QTcF) formulaXx_NEWLINE_xXFridericia's corrected QT (QTcF) interval > 500 msec\r\nNote: Three electrocardiograms (ECGs) must be performed for eligibility determination; if the average of these three consecutive results for QTcF is =< 500 msec, the subject meets eligibility in this regardXx_NEWLINE_xXCardiac electrophysiologic stability as defined by an electrocardiogram (ECG) with a corrected QT (QTc) interval < 500 msec at screeningXx_NEWLINE_xXPositive risk assessment for cardiovascular disease including prior anthracycline cumulative dose more than 50% above recommended non-cardiotoxic levels, left ventricular ejection fraction (LVEF) <50%, valvular heart disease, or severe hypertension, (see Table 1). Cardiac subjects with a New York Heart Association (NYHA) classification of 3 or 4 will be excluded. (Cardiology consultation should be requested if any question arises about cardiac function.) This also includes subjects with baseline QT/QTc interval >480 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.Xx_NEWLINE_xXCorrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 7 days before starting study treatment\r\n* Note: if the QTcF is > 500 ms in first electrocardiography (ECG), a total of 3 ECGs should be performed; if the average of these 3 consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regardXx_NEWLINE_xXElectrocardiogram (ECG) abnormalities:\r\n* Prolonged corrected QT (QTc) (Bazette’s or Fredericia’s correction) interval on screening ECG (>= 450 msec)\r\n* QRS ? 120 msec\r\n* PR ? 210 msec\r\n* Any prior history, or current evidence of second- or third-degree heart block\r\n* Heart rate ? 40 beats per minute at screening\r\n* ECG second degree heart block (Mobitz’s type 2 or Wenckebach)\r\n* Complete heart block\r\n* Left bundle branch block or bifascicular block (right bundle branch block and left anterior hemiblock together)\r\n* Episodes of ventricular tachycardiaXx_NEWLINE_xXUnstable or serious concurrent medical conditions in the previous 6 months, eg, pancreatitis, severe/unstable angina, prolonged QT interval corrected by Fridericia’s formula (QTcF) > 470 msec (calculated as average of triplicate readings, taken no greater than 2 minutes apart, and no history of torsades de pointes or symptomatic corrected QT [QTc] abnormality), symptomatic congestive heart failure, myocardial infarction and/or pulmonary hypertension, ongoing maintenance therapy for life-threatening ventricular arrhythmia, stroke, and uncontrolled major seizure disorderXx_NEWLINE_xXUnstable cardiac dysrhythmias or persistent prolongation of the corrected QT interval (QTc) (Fridericia) to >480 msec for males or >500 msec for females, based on ECG at screening (patients with stable atrial fibrillation on treatment are allowed provided they do not meet any other cardiac or prohibited drug exclusion criterion);Xx_NEWLINE_xXPatients with a corrected QT (QTc) interval of > 450 milliseconds (msec) on screening electrocardiogram (ECG) for men or > 470 msec for womenXx_NEWLINE_xXHave a Fridericia's QT corrected interval (QTcF) interval of >450 milliseconds (msec) for males and >470 msec for females on screening electrocardiogram (ECG) utilizing Fridericia's correction.Xx_NEWLINE_xXBaseline electrocardiogram (EKG) shows corrected QT interval by Fredericia (QTcF) > 470 msec.Xx_NEWLINE_xXMean QT interval corrected for heart rate using Fridericia’s formula (QTcF) >= 470 ms; abnormality must be confirmed on 3 electrocardiography (ECG)sXx_NEWLINE_xXResting electrocardiogram (ECG) with corrected QT Interval (QTc) > 470 msec on 2 or more time points within a 24-hour period or family history of long QT syndrome.Xx_NEWLINE_xXBaseline prolongation of the QT interval corrected for heart reate (HR) using Fridericia's formula (QT interval corrected for heart rate using Fridericia's formula (QTcF); example, repeated demonstration of QTcF interval >480 millisecond (ms), history of congenital long QT syndrome, or torsades de pointes).Xx_NEWLINE_xXPatients with QTc interval > 480 msec or those known to have congenital long QTc syndrome.Xx_NEWLINE_xXQT interval corrected for heart rate using Fridericia’s formula (QTcF) >= 470 ms; (any clinically significant abnormalities detected require triplicate electrocardiogram [ECG] results and a mean QT interval corrected for heart rate using Fridericia’s formula (QTcF) >= 470 ms calculated from 3 ECGs)Xx_NEWLINE_xXHas a mean QTcF prolongation >470 ms for females and >450 ms for males in three successive Screening measurements.Xx_NEWLINE_xXSubject has familial short QT syndrome, is receiving medications that are known to shorten the QT interval, or has a clinically significant abnormal electrocardiogram (ECG).Xx_NEWLINE_xXCorrected QT using Fridericia's formula (QTcF) prolongation.Xx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from electrocardiograms (ECGs) using Bazett’s correctionXx_NEWLINE_xXFridericia's correction formula (QTcF) > 500 msec within 1 month before the first dose of study treatment:\r\n* Three electrocardiography (ECG)s must be performed for eligibility determination; if the average of these three consecutive results for QTcF is =< 500 msec, the subject meets eligibility in this regardXx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s correctionXx_NEWLINE_xXQT interval corrected for heart rate using Fridericia’s formula (QTcF) >= 470 ms. Any clinically significant abnormalities detected, require triplicate electrocardiogram (ECG) results and a mean QT interval corrected for heart rate using Fridericia’s formula (QTcF) >= 470 ms calculated from 3 ECGs.Xx_NEWLINE_xXCorrected QT (QTc) > 470 milliseconds (msec) on a 12-lead ECG obtained during the screening period; Note: If a machine reading is above this value, the ECG should be reviewed by a qualified reader and confirmed on a subsequent ECGXx_NEWLINE_xXCorrected QT using Fridericia's formula (QTcF) > 500 msec within 1 month before the first dose of study treatment:\r\n* Three electrocardiogram (ECG)s must be performed for eligibility determination; if the average of these three\r\nconsecutive results for QTcF is =< 500 msec, the subject meets eligibility in this regardXx_NEWLINE_xXMean QT interval corrected for heart rate using Fridericia’s formula (QTcF) >= 470 ms calculated from 3 electrocardiograms (ECGs) (within 15 minutes at 5 minutes apart)Xx_NEWLINE_xXHas history or presence of an abnormal electrocardiogram (ECG) which, in the investigator's opinion, is clinically significant\r\n* Corrected QT Fredericia's formula (QTcF) >= 480 ms or presence of a left bundle branch block (LBBB); if the QRS duration > 120ms, the JTc can be used in place of the QTcF; the JTc must be < 340 msXx_NEWLINE_xXScreening 12-lead ECG with a measurable QTc interval according to Fridericia's correction >450 ms.Xx_NEWLINE_xXKnown mean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s correction. (Note that ECG is not required for study entry and is not part of study procedures)Xx_NEWLINE_xXPatients with a corrected QT (QTc) > 480 ms in the baseline electrocardiography (EKG)Xx_NEWLINE_xXKnown QT interval prolongationXx_NEWLINE_xXProlongation of corrected QT (QTc) interval to >480 milliseconds (msec) when electrolyte balance is normalXx_NEWLINE_xXHas a QT interval corrected for heart rate (QTc) > 470 ms using the Fridericia formula; if the screening electrocardiogram (ECG) has a QTc > 470ms, the mean QTc of 3 electrocardiograms (ECGs) can be utilized, but must be < 470 msXx_NEWLINE_xXCorrected QT (QTc) (Fridericia Correction Formula) > 480 ms on electrocardiogram (ECG)Xx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from a baseline electrocardiogram using Fridericia’s correctionXx_NEWLINE_xXA single QT interval corrected for heart rate (QTc) >= 470 ms. If an electrocardiogram (ECG) is interpreted to be a prolonged QT interval, 2 additional ECGs will be obtained and the PI will then evaluate all three ECGs and determine whether the patient should be excluded. Mean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s correctionXx_NEWLINE_xXQT interval corrected for heart (QTc) >= 470 ms calculated from 1 electrocardiogram (ECG) using Fridericia's correctionXx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia’s correctionXx_NEWLINE_xXElectrocardiogram (ECG) - corrected QT (QTc) < 480 msec, within 2 weeks of registration (except where specified otherwise)Xx_NEWLINE_xXQTc interval of ? 450 msec (males) or 470 msec (females) calculated according to Fridericia's formula (QTc = QT/RR0.33; RR=RR interval)Xx_NEWLINE_xXA QTc interval outside of normal. (Normal: < 450 msec for males and < 460 msec for females)Xx_NEWLINE_xXCorrected QT (QTc) interval > 0.450 seconds (males) or > 0.470 seconds (females), or known history of QTc prolongation or Torsade de Pointes (TdP)Xx_NEWLINE_xXScreening rate-corrected QT interval (QTc) must be <450msec and a resting heart rate of at least 50-90 bpm via a standard 12-lead ECG within 28 days prior to registration.Xx_NEWLINE_xXHave normal QT interval on electrocardiogram (ECG) evaluation QT corrected Fridericia (QTcF) of =< 450 ms in males or =< 470 ms in femalesXx_NEWLINE_xXMean QT interval corrected for heart rate (corrected QT interval [QTc]) >= 470 ms calculated from electrocardiogram (in triplicate, if applicable) using Fridericia’s correctionXx_NEWLINE_xXProlongation of QT/ corrected QT (QTc) interval (QTc interval > 450 ms for males or > 470 ms for females) using the Fridericia method of QTc analysis.Xx_NEWLINE_xXScreening electrocardiogram (ECG) (defined as the mean of the triplicate ECGs) with QTcF interval at screening =< 450 msec (using Fridericia’s correction) and resting heart rate >= 50 bpmXx_NEWLINE_xXSubjects with a corrected QT (QTc) > 480 ms (QTc > 510 msec for subjects with a bundle branch block at baseline)Xx_NEWLINE_xXResting electrocardiogram (ECG) with corrected QT (QTc) > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndromeXx_NEWLINE_xXCorrected QT (QTc) > 500ms at baseline (average of 3 determinations at 10 minute intervals)Xx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s correction.Xx_NEWLINE_xXAny of the following cardiac criteria: Mean resting corrected QTc interval using the Fridericia formula (QTcF) greater than 450 msec/male and greater than 470 msec/female or congenital long QT syndromeXx_NEWLINE_xXMarked baseline prolongation of QT/corrected QT interval (QTc) interval (e.g. demonstration of a QTc interval greater than 500 milliseconds)Xx_NEWLINE_xXScreening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) > 500 milliseconds (msec). Participants who have a pacemaker may be included regardless of calculated QTc intervalXx_NEWLINE_xXBaseline corrected QT Interval (QTc) > 470 milliseconds (msec) in women and > 450 msec in men; concomitant treatment with medications that prolong the QT interval and have a known risk of Torsades De Pointes is not contraindicated, but should be avoided if possible and will require more frequent electrocardiogram (EKG) monitoringXx_NEWLINE_xXThe subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before randomization; Note: if initial QTcF is found to be > 500 ms, two additional electrocardiogram (EKG)s separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regardXx_NEWLINE_xX12?lead electrocardiogram (ECG) demonstrating QT interval corrected by Fridericia's formula >450 ms in males or >470 ms in females at screening or history of long QT interval corrected syndrome.Xx_NEWLINE_xXProlonged corrected QT interval by the Fridericia correction formula (QTcF) on screening electrocardiogram (EKG) > 480 msecXx_NEWLINE_xXResting electrocardiogram (ECG) with corrected QT (QTc) > 470 msec on 2 or more time points within a 24 hour period or of long QT syndromeXx_NEWLINE_xXBaseline prolongation of the rate-corrected QT interval (QTc; example, repeated demonstration of QTc interval > 480 millisecond [ms], or history of congenital long QT syndrome, or torsades de pointes).Xx_NEWLINE_xXCorrected QT interval (QTc) > 480 msec on screening electrocardiogram; if QTc prolongation is felt to be related to electrolyte imbalance, an electrocardiogram (EKG) can be repeated after correction of electrolytesXx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s correctionXx_NEWLINE_xXSignificant screening electrocardiogram (ECG) abnormalities including, but not limited to, left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) >= 470 msec; subjects with a cardiac pacemaker who have a QTc interval of >= 470 msec may be eligible if these findings are considered not clinically significant as documented via a cardiology evaluationXx_NEWLINE_xXConcurrent therapy with medications known to prolong the QT interval and/or associated with Torsade de Pointes arrhythmiaXx_NEWLINE_xXCorrected QT interval ([QTc] Fridericia) > 480 msXx_NEWLINE_xXSignificant screening electrocardiogram (ECG) abnormalities including, but not limited to, left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) >= 470 msec; subjects with a cardiac pacemaker who have a QTc interval of >= 470 msec may be eligible if these findings are considered not clinically significant as documented via a cardiology evaluationXx_NEWLINE_xXProlonged rate corrected QT (QTc) interval of > 500 msec, calculated according to institutional guidelinesXx_NEWLINE_xXMeets the following standard 12-lead electrocardiography (ECG) parameters at screening (defined as the mean of the triplicate ECGs):\r\n* Corrected QT using Fridericia's correction formula (QTcF) interval at screening < 450 msec for males and < 470 msec for females\r\n* Resting heart rate =< 100 beats per minute (bpm)Xx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's correctionXx_NEWLINE_xXPatients with available standard 12-lead electrocardiography (ECG) with the following parameters at screening (defined as the mean of the triplicate ECGs):\r\n* Fridericia's correction formula (QTcF) interval at screening < 450 msec\r\n* Resting heart rate 50-90 beats per minute (bpm)Xx_NEWLINE_xXCardiovascular disorders such as:\r\n* Inability to monitor the QT interval on electrocardiogram (ECG)\r\n* Complete left bundle branch block\r\n* Right bundle branch block plus left anterior or posterior hemiblock\r\n* Use of a ventricular-paced pacemaker\r\n* Congenital long QT syndrome or a known family history of long QT syndrome\r\n* Clinically significant resting bradycardia (< 50 beats per minute)\r\n* Corrected QT interval (QTc) > 450 msec on baseline ECG; if QTc > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc\r\n* Myocardial infarction within 6 months prior to starting study\r\n* History of unstable angina within 6 months prior to study entry\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 or atrial tachyarrhythmiasXx_NEWLINE_xXRate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead ECG during screeningXx_NEWLINE_xXCorrected QT interval calculated by the Bazett formula (QTcB) > 480 msecXx_NEWLINE_xXMean QT interval corrected for heart rate (QTcF) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s CorrectionXx_NEWLINE_xXMean resting corrected QT interval (QTc) >470 msecXx_NEWLINE_xXPatients, who continue to have prolonged corrected QT (QTc) (males: > 450 ms; females: > 470 ms as calculated by Fridericia’s correction formula) despite normal electrolyte balance and discontinuation of medications known to prolong QTc, will be excluded from the studyXx_NEWLINE_xXQTcF interval at screening <450 msec (using Fridericia's correction)Xx_NEWLINE_xXMarked baseline prolongation of QT/corrected QT (QTc) interval (QTc interval >= 500 msec) using the Fridericia method (QTc = QT/RR0.33) for QTc analysisXx_NEWLINE_xXClinically active cardiac disease, including prolonged corrected QT (QTc) interval >= 481 ms (i.e. >= grade 2)Xx_NEWLINE_xXScreening 12-lead electrocardiogram (ECG) with a measurable QTc interval according to Fridericia’s correction > 450 msXx_NEWLINE_xXBaseline corrected QT interval (corrected QT interval by Fridericia's formula [QTcF]) < 480 msXx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s CorrectionXx_NEWLINE_xXBaseline prolongation of QT/QTc interval (repeated demonstration of QTc ? 450 msec for men and 470 msec for women, or LVEF ? 40% by MUGA or ECHO).Xx_NEWLINE_xXAdequate cardiac function defined as\r\n* No history of congenital QTc syndrome, New York Heart Association (NYHA) class III or IV congestive heart failure (CHF)\r\n* No clinical significant cardiac arrhythmias, stroke or myocardial infarction within 6 months prior to enrollment\r\n* QTc =< 480 msec; Note: Three electrocardiograms (ECGs) must be performed for eligibility determination; if the average of these three consecutive results for corrected QT using Fridericia's formula (QTcF) is =< 480 msec, the subject meets eligibility in this regard; patients with grade 1 prolonged QTc (450-480 msec) at the time of study enrollment should have correctable causes of prolonged QTc addressed if possible (i.e. electrolytes, medications)Xx_NEWLINE_xXBaseline electrocardiogram demonstrating all of the following: corrected QT (QTc) < 450 milliseconds (msec) (men) and < 470 msec (women), PR < 240 msec, QRS < 100 msecXx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia’s correctionXx_NEWLINE_xXMean QT interval corrected for heart rate (corrected QT [QTc]) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s correctionXx_NEWLINE_xXElectrocardiogram (EKG) corrected QT interval (QTc) < 450 msec (females)Xx_NEWLINE_xXBaseline Fridericia's corrected QT (QTcF) interval of > 470 ms, participants with baseline resting bradycardia < 45 beats per minute, or baseline resting tachycardia > 100 beats per minuteXx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from an electrocardiograms (ECGs) using Bazett’s Correction; if first ECG is abnormal, then the mean will be calculated from 3 consecutive ECGs (taken 2-5 minutes apart); please contact the PI for further clarificationXx_NEWLINE_xXPART 2 GROUP 1 INCLUSION CRITERIA: Corrected QTc =< 480 msecXx_NEWLINE_xXPART 2 GROUP 2A INCLUSION CRITERIA: Corrected QTc =< 480 msecXx_NEWLINE_xXPART 2 GROUP 3 INCLUSION CRITERIA: Corrected QTc =< 480 msecXx_NEWLINE_xXCorrected QT (QTc) =< 450 msec. for men or QTc =< 470 msec. for womenXx_NEWLINE_xXPHASE I AND II SCLC AND UROTHELIAL CARCINOMA EXPANSION COHORT: Prolongation of QT/corrected QT (QTc) interval (QTc interval > 500 msec) using the Fridericia method of QTc analysis or family history of long QT syndrome; if single reading is above these minimum ranges, then repeat test in triplicate and evaluate eligibility based on average valueXx_NEWLINE_xXmCRPC EXPANSION COHORT: Prolongation of QT/QTc interval (QTc interval > 500 msec) using the Fridericia method of QTc analysis or family history of long QT syndrome; if single reading is above these minimum ranges, then repeat test in triplicate and evaluate eligibility based on average valueXx_NEWLINE_xXA corrected QT interval (QTc) ? 480 msec using the Fridericia's formula (QTcF)Xx_NEWLINE_xXAny of the following cardiac criteria\r\n* Resting corrected QT interval (QTc using Fridericia’s formula) > 480 msec\r\n* Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiograph (ECG) (e.g., complete left bundle branch block, third degree heart block, second degree heart block)\r\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval \r\n** Symptomatic congestive heart failure or left ventricular ejection fraction (LVEF) < 50%Xx_NEWLINE_xXFridericia's corrected QT interval (QTcF) > 470 msec using the Fredericia formulaXx_NEWLINE_xXNormal electrocardiogram with corrected QT (QTc) =< 450Xx_NEWLINE_xXSignificant screening electrocardiogram (ECG) abnormalities including, but not limited to, left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) >= 470 msec; subjects with a cardiac pacemaker who have a QTc interval of >= 470 msec may be eligible if these findings are considered not clinically significant as documented via a cardiology evaluationXx_NEWLINE_xXQTc prolongation >470 msec or other significant ECG abnormality noted within 14 days of treatmentXx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Bazett’s correctionXx_NEWLINE_xXMedications known to prolong corrected QT (QTC) are not allowedXx_NEWLINE_xXCorrected QT Interval Fridericia (QTcF) > 450 msec (both genders)Xx_NEWLINE_xXProlonged corrected QT (QTc) interval on pre-entry electrocardiogram (>= 450 msec)Xx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s correctionXx_NEWLINE_xXResting electrocardiogram (ECG) with corrected QT interval (QTc) > 470 msec (Fridericia’s scale)Xx_NEWLINE_xXPatients with clinically relevant abnormal electrocardiography (ECG) findings, including abnormal corrected QT interval (QTc) > 500 ms on screening ECG (note: if a patient has a QTc interval > 500 ms on screening ECG, the screening ECG may be repeated twice [at least 24 hours apart] for a total of 3 ECGs)Xx_NEWLINE_xXCorrected QT interval (QTc) > 470 msec (as calculated per institutional standards) at study entry or congenital long QT syndromeXx_NEWLINE_xXQT interval corrected for rate (QTc) ? 480 msec on the electrocardiogram (ECG) obtained at ScreeningXx_NEWLINE_xXFridericia's correction formula (QTcF) > 480 msec (males and females)Xx_NEWLINE_xXCorrected QT (QTc) interval =/< 470 msecs, no familial history of QTc prolongation or ventricular arrhythmiasXx_NEWLINE_xXBaseline prolongation of QT/QTc interval (repeated demonstration of QTc ? 450 msec for men and 470 msec for women), or LVEF ? 40% by MUGA or ECHO.Xx_NEWLINE_xXCorrected QT interval (QTc) value > 480 msec at screening; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy at screening; previous history of drug-induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on electrocardiogram (EKG); if QTc prolongation on screening EKG is felt to be related to electrolyte imbalance, an EKG can be repeated after correction of electrolytesXx_NEWLINE_xXCorrected QT (QTc) interval > 480 ms (>= grade 2) on a 12-lead electrocardiogram (ECG)\r\n* If baseline QTc on screening ECG is >= grade 2:\r\n** Check potassium and magnesium serum levels\r\n** Correct any identified hypokalemia and/or hypomagnesemia and repeat ECG to confirm exclusion of patient due to QTc\r\n* For patients with heart rate < 60 beats per minute (bpm) or > 100 bpm, manual read of the QT interval by a cardiologist is required, with Fridericia correction applied to determine Fridericia QTc (QTcF) which must be used to determine eligibility\r\n* Note: If heart rate is 60-100 bpm, manual read of the QT interval and correction to QTcF is not requiredXx_NEWLINE_xXPatient with available standard 12-lead electrocardiogram (ECG) with the following parameters at screening (defined as the mean of the triplicate ECGs):\r\n* Corrected QT interval using Fridericia's formula (QTcF) at screening < 450 msec (using Fridericia’s correction)\r\n* Resting heart rate 50-90 bpmXx_NEWLINE_xXSubjects with prolongation of corrected QT interval by Fridericia’s method (QTcF) at rest, where the mean QTcF interval is > 450 milliseconds (ms) for males and > 470 ms for females based on triplicate electrocardiogram (ECG)Xx_NEWLINE_xXPHASE I: Resting electrocardiogram (ECG) with corrected QT QTc) > 470msec on two or more time points within a 24h period, or a family history of long QT syndromeXx_NEWLINE_xXQTc > 450ms, history of Qtc prolongation or predisposition for QTc prolongation or family history of sudden cardiac death or QT prolongationXx_NEWLINE_xXMean corrected QT interval (QTc) > 480 msec or any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in a next-of-kin relative.Xx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 2 electrocardiograms (ECGs) using Bazett’s correction; two electrocardiogram (EKGs) 5 minutes (+/- 2 min) apart is mandatoryXx_NEWLINE_xXPatients with baseline corrected QT (QTc) > 470 ms or patients with symptomatic bradycardiaXx_NEWLINE_xXCongenital QT syndrome, corrected QT (QTc) > 500 msXx_NEWLINE_xXMean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value.Xx_NEWLINE_xXAny factors that increase the risk of QTc prolongation or risk of arrhythmic events, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval.Xx_NEWLINE_xXCorrected QT (QTc) interval > 480 msec, family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de PointesXx_NEWLINE_xXThe subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before treatment; note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regardXx_NEWLINE_xXQTcF (Fridericia formula for the QT interval correction for the heart rate) > 480 msec within 4 weeks of enrollment; if the initial QTcF is found to be > 480 msec, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =< 480 msec, the subject meets eligibility in this regard; subjects with history of congenital long QT syndrome, or torsades de pointes, are not allowedXx_NEWLINE_xXHas a QT interval corrected by Fridericia's formula (QTcF) ?480 msecXx_NEWLINE_xXHave normal QT interval corrected (Frederica) (QTcF) interval on screening electrocardiogram (ECG) evaluation, defined as QTcF of ? 450 ms in males or ? 470 ms in females.Xx_NEWLINE_xXCorrected QT (QTc) =< 480 msXx_NEWLINE_xX12-lead electrocardiogram (EKG) showing no active ischemia and corrected QT (QTc) interval less than 480 msecXx_NEWLINE_xXPatients must not have corrected QT (QTc)F (Fridericia Correction Formula) > 480 on 2 out of 3 electrocardiograms (EKG’s) (if first EKG is =< 480, no need to repeat, if first EKG is > 480 repeat twice for a total of 3 EKG’s)Xx_NEWLINE_xXFridericia corrected QT (QTcF) correction unmeasurable or > 450 ms on screening ECG (Note: If a patient has a QTcF interval > 450 ms on screening ECG, the screening ECG may be repeated twice [at least 24 hours apart] for a total of 3 ECGs; the average QTcF from the three screening ECGs must be =< 450 ms in order for the patient to be eligible for the study)Xx_NEWLINE_xXResting electrocardiogram (ECG) with QTc > 470 msec on 2 or more time points within a 24-hour period or family history of long QT syndromeXx_NEWLINE_xXSubject has corrected QT (QTc) interval < 500 msec on baseline electrocardiogramXx_NEWLINE_xXQT interval corrected for rate (QTc) ? 480 msec on the electrocardiogram (ECG) obtained at Screening (average of 3 readings)Xx_NEWLINE_xXA clinically significant ECG abnormality, including a marked baseline prolonged QT or QTc interval (eg, a repeated demonstration of a QTc interval greater than 480 msec).Xx_NEWLINE_xXCorrected QT interval (QTc) =< 480 msecXx_NEWLINE_xXRate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead electrocardiogram (ECG) during screeningXx_NEWLINE_xXScreening electrocardiography (ECG) with corrected QT (QTc) interval > 480 milliseconds (corrected by Fridericia); in the event that a single QTc is > 480 msec, the subject may enroll if the average QTc for 3 ECGs is < 480 msecXx_NEWLINE_xXAbnormalities on 12-lead electrocardiogram (ECG) considered by the investigator to be clinically significant (such as acute ischemia, left bundle branch block, ventricular arrhythmias) or baseline prolongation of the rate-corrected QT interval (e.g., repeated demonstration of QTc interval > 480 milliseconds)Xx_NEWLINE_xXCorrected QT(c) >= 481 ms (>= grade 2) on electrocardiogram (ECG) prior to initiation of treatment\r\n* If baseline QTc on screening ECG meets exclusion criteria:\r\n** Check potassium and magnesium serum levels\r\n** Correct any identified hypokalemia and/or hypomagnesemia and repeat ECG to confirm exclusion of patient due to QTc\r\n* For patients with HR 60-100 bpm, no manual read of QTc is required\r\n* For patients with baseline HR < 60 or > 100 bpm, manual read of QT by cardiologist is required, with Fridericia correction applied to determine QTcXx_NEWLINE_xXEvidence of currently uncontrolled cardiovascular conditions as listed in the protocol; acute myocardial infarction with 6 months before starting study drug; baseline QT interval (QTcF) greater than (>) 450 milliseconds (msec) (males) or > 475 msec (females); or abnormalities on baseline 12-lead electrocardiogram (ECG) that are considered clinically significant per investigator.Xx_NEWLINE_xXProlongation of corrected QT interval by Fridericia's method (QTcF) at rest, where the mean QTcF interval is >450 ms for males or >470 ms for females based on triplicate electrocardiograms (ECGs).Xx_NEWLINE_xXCorrected QT interval (QTc) > 500 ms at baselineXx_NEWLINE_xXA corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before first dose of study treatment; three electrocardiograms (ECGs) must be performed; if the average of these three consecutive results for QTcF is =< 500 msec, the subject meets eligibility in this regardXx_NEWLINE_xXPatients with prolonged corrected QT interval, defined as corrected QT (QTc) > 450 msecXx_NEWLINE_xXCorrected QT (QTc) interval >= 480 msec (>= 500 msec for subjects with bundle branch block)Xx_NEWLINE_xXBaseline QTc >470 msec measured by Fridericia's formula (QTcF) and/or previous history of QT prolongation while taking other medications. Concomitant use of medications associated with a high incidence of QT prolongation is not allowed.Xx_NEWLINE_xXPatients with known prolonged corrected QT (QTc) syndrome or prolonged QTc syndrome noted on baseline electrocardiography (ECG)Xx_NEWLINE_xXCorrected QT interval (QTc) > 480 msecsXx_NEWLINE_xXQT interval corrected using Fridericia’s method (QTcF) < 460 msecXx_NEWLINE_xXHistory of serious ventricular arrhythmia (VT or VF, ? 3 beats in a row), QTc ? 450 msec for men and 470 msec for women, or LVEF ? 40% by MUGA or ECHO.Xx_NEWLINE_xXBaseline cardiac QTc interval > 450 msecsXx_NEWLINE_xXBaseline prolongation of the rate-corrected QT interval (QTc) (e.g. repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes)Xx_NEWLINE_xXThe subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before randomization; Note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regardXx_NEWLINE_xXHistory of or ongoing cardiac dysrhythmias requiring treatment, atrial fibrillation of any grade, or persistent prolongation of the QTc (Fridericia) interval to > 450 msec for males or > 470 msec for females.Xx_NEWLINE_xXCorrected QT interval using Fridericia's formula (QTcF) interval less than or equal to 480 ms (Phase II only)Xx_NEWLINE_xXPatients with mean QTcF values of > 470 msec (in females) or > 450 msec (in males) following 3 ECGs conducted 5 minutes apart from each other; patients who are known to have congenital prolonged QT syndromes; or patients who are on medications known to cause prolonged QT intervals on ECG.Xx_NEWLINE_xXThe subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before randomization; Note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regardXx_NEWLINE_xXCorrected QT (QTc) interval =< 480 ms by electrocardiogram (EKG)Xx_NEWLINE_xXBaseline electrocardiogram (EKG) with corrected QT interval (QTc) > 470 msec (including subjects on medication); subjects with ventricular pacemaker for whom QT interval is not measurable will be eligible on a case-by-case basisXx_NEWLINE_xXHave chronic atrial fibrillation or QTc of greater than 470 msec, as calculated by Bazett's correction formula.Xx_NEWLINE_xXRelapsed/refractory MCL: Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, bradycardia (< 50 beats per minute [bpm]), or corrected QT (QTc) > 500 msecXx_NEWLINE_xXScreening electrocardiogram (ECG) with a corrected QT interval (QTc) > 460 msec confirmed by central laboratory prior to enrollment to the studyXx_NEWLINE_xXCorrected QT (QTc) > 480 ms (grade 2 or greater) on screening electrocardiogram (ECG)\r\n* If baseline QTc on screening ECG meets exclusion criteria on screening assessment:\r\n** Check potassium and magnesium levels\r\n** Correct any identified hypokalemia and/or hypomagnesemia and repeat ECG to confirm exclusion of patient due to QTc\r\n** For patients with a heart rate (HR) 60-100 bpm, no manual read of QT is required\r\n** For patients with baseline HR < 60 or > 100 bpm, manual read of QT by cardiologist is required using Fridericia correctionXx_NEWLINE_xXPatients with QTc > 480 msec.Xx_NEWLINE_xXPatients with the following cardiac diagnoses: ventricular tachycardia or fibrillation; Torsades de pointes; clinically significant bradycardia; sinus node dysfunction; heart block; prolonged corrected QT (QTc) interval (QTc > 450 milliseconds for males, QTc > 470 milliseconds for females); valvular, ischemic, or pulmonary heart disease; cardiomyopathy; history of heart failureXx_NEWLINE_xXPatient has a history or current evidence of clinically significant heart disease including:\r\n* Clinically significant congestive heart failure, unstable angina pectoris\r\n* Clinically significant cardiac arrhythmia\r\n* Myocardial infarction during the last 6 months, and/or a current electrocardiogram (ECG) tracing that is abnormal in the opinion of the treating Investigator\r\n* Corrected QT interval (QTc) prolongation > 480 msec (Bazett's formula)\r\n* Congenitally long QT syndrome, and/or current anti-arrhythmic therapy, and / or has received any marketed or experimental compound in the last 1 week prior to entering the study with known effects of QT prolongationXx_NEWLINE_xXPonatinib\r\n* Female and male patients who are fertile must agree to use an effective form of contraception with their sexual partners from randomization through 4 months after the end of treatment\r\n* Discontinuation of any medications known to contribute significantly to the risk of QT prolongation at least 48 hours prior to start of study drug; Levaquin and Zofran are an exception; of note, certain agents that prolong the corrected QT interval (QTc) may be allowed but only after discussion with the chemotherapy pharmacist; should the investigator believe that therapy with a potentially QT prolonging medication is vital to an individual subject’s care, then additional electrocardiograms (ECGs) should be done at the investigator’s discretion to ensure the subject’s safety\r\n* Serum lipase =< 1.5 x ULN\r\n* Serum amylase =< 1.5 x ULNXx_NEWLINE_xXNilotinib\r\n* Normal QTc interval on screening ECG evaluation, defined as < 450 msec for men and < 470 msec for women\r\n* Discontinuation of any medications known to contribute significantly to the risk of QT prolongation at least 48 hours prior to start of study drug; Levaquin and Zofran are an exception; of note, certain agents that prolong the corrected QT interval may be allowed but only after discussion with the chemotherapy pharmacist; should the investigator believe that therapy with a potentially QT prolonging medication is vital to an individual subject’s care, then additional ECGs should be done at the investigator’s discretion to ensure the subject’s safetyXx_NEWLINE_xXCorrected QT for Fridericia (QTcF) interval greater than 500 ms that is not correctable to less than 500 ms such as with cessation of a causative medication, etcXx_NEWLINE_xXCorrected QT (QTc) prolongation > 480 msec (Bazett's formula) or congenitally long QT syndromeXx_NEWLINE_xXCorrected QT interval (QTc) > 480 msecs using Bazett‘s formulaXx_NEWLINE_xXSyndrome of congenital corrected QT interval (QTc) prolongation or QTc > 500 msecXx_NEWLINE_xXAny of the following cardiac criteria:\r\n* Mean resting corrected QT interval (Fridericia's correction formula [QTcF]) > 470 ms ms obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived corrected QT (QTc) value\r\n* Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block)\r\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT intervalXx_NEWLINE_xXCorrected QT (QTc) > 470 milliseconds (msec) on a 12-lead ECG obtained during the Screening period\r\n* Note: If a machine reading is above this value, the ECG should be reviewed by a qualified reader and confirmed on a subsequent ECGXx_NEWLINE_xXScreening corrected QT interval (QTc) interval > 470 millisecondsXx_NEWLINE_xXQTcF >470 msec on screening ECG or congenital long QT syndromeXx_NEWLINE_xXBaseline Fridericia corrected QT (QTcF) > 480 ms; NOTE: this criterion does not apply to patients with a left bundle branch blockXx_NEWLINE_xXFridericia corrected QT (QTcF) interval on the electrocardiogram (EKG) greater than 480 millisecondsXx_NEWLINE_xXHistory or presence of an abnormal electrocardiogram (ECG) that, in the Investigator's opinion, is clinically meaningful. Screening QTcF interval >480 ms is excluded. In the event that a single QTcF is >480 ms, the subject may enroll if the average QTcF for the 3 ECGs is < 480ms. For patients with an intraventricular conduction delay (QRS interval >120ms), the JTc interval may be used in place of the QTcF with Sponsor approval. The JTc must be <340 ms if JTc is used in place of the QTcF. Patients with an intraventricular delay due to a left bundle branch block are excluded; Note: QTcF prolongation due to pacemaker may enroll if the JTc is normal.Xx_NEWLINE_xXQTc interval > 450 msecXx_NEWLINE_xXMean resting corrected QT interval (QTc) >450 millisecond (msec), obtained from 3 ECGs recordings, using the screening clinic ECG machine-derived QTc value.Xx_NEWLINE_xXQTcF >450 milliseconds (msec) or QTcF >480 msec for subjects with bundle branch blockXx_NEWLINE_xXQT interval corrected for heart rate (QTc) (corrected by Fridericia's method) > 450 msec at ScreeningXx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 consecutive electrocardiograms (EKGs) using Fridericia’s correction at baseline or before dosingXx_NEWLINE_xXAny of the following cardiac criteria: Mean resting QT interval corrected for heart rate (QTc) more than 470 msec, obtained from 3 ECGs, using the screening clinic ECG machine derived QTc value. Any clinically important 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. 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 40 years of age in first degree relatives or any concomitant medication known to prolong the QT intervalXx_NEWLINE_xXProlonged rate corrected QT (QTc) interval >= 500 msec, calculated according to institutional guidelinesXx_NEWLINE_xXProlonged QTc greater than or equal to 470 ms. If QTc greater than or equal to 470ms, confirmation of eligible QTc requires mean calculation from 2 additional electrocardiograms (ECGs) 2?5 minutes apart using Fridericia's Correction Formula (mean less than 470 ms).Xx_NEWLINE_xXMarked baseline prolongation of QT/corrected QC (QTc) interval (e.g. demonstration of a QTc interval greater than 500 milliseconds)Xx_NEWLINE_xXInterval from the Q wave on the ECG to point T using Fredericia's formula (QTcF) > 500 millisecond (msec)Xx_NEWLINE_xXQTcF interval >470 ms on screening ECG.Xx_NEWLINE_xXHas a corrected QT prolongation to > 450 millisecond (ms) in males and > 470 ms in femalesXx_NEWLINE_xXScreening ECG QTc interval 470 msec for females, 450 msec for males.Xx_NEWLINE_xXAt increased risk for developing prolonged QT interval unless corrected to within normal limits prior to first dose of SNX-5422Xx_NEWLINE_xXScreening ECG QTc interval 470 msec for females, 450 msec for males.Xx_NEWLINE_xXAt increased risk for developing prolonged QT interval unless corrected to within normal limits prior to first dose of SNX-5422Xx_NEWLINE_xXScreening corrected QT (QTc) interval >= 450 msec for males or >= 470 msec for females; PR interval > 250 msec for males and females within 4 weeks prior to start of any therapyXx_NEWLINE_xXOn ECG a QTc(F) interval >480 msec or any clinically significant cardiac rhythm abnormalities.Xx_NEWLINE_xXCorrected QT interval (QTc) > 480 msecs using Bazett's formulaXx_NEWLINE_xXPatients must have an electrocardiogram (EKG) within 28 days prior to registration according to the following parameters:\r\n* Male patients must have a corrected QT (QTc) =< 450 ms\r\n* Female patients must have a QTc =< 470 msXx_NEWLINE_xXQT intervals of QTc ? 500 msecXx_NEWLINE_xXCorrected QT interval (QTc) prolongation > 450 milliseconds (msec)Xx_NEWLINE_xXBaseline QTc > 470 msec or previous history of QT prolongation while taking other medicationsXx_NEWLINE_xXQTc interval < 450 msXx_NEWLINE_xXBaseline QT interval corrected with Fridericia's method (QTcF) >480 ms NOTE: this criterion does not apply to subjects with a right or left bundle branch block (BBB)Xx_NEWLINE_xX206 Baseline electrocardiogram (ECG) QTc > 470 msec.Xx_NEWLINE_xXHas a corrected QT interval (QTc) > 470 ms or has an electrocardiogram (ECG) with a new abnormal finding that is clinically significant.Xx_NEWLINE_xXMean resting corrected QTc interval using the Fridericia formula (QTcF) > 450 msec/male and > 470 msec/female (as calculated per institutional standards) obtained from 3 electrocardiograms (ECGs) 2-5 minutes apart at study entry, or congenital long QT syndromeXx_NEWLINE_xXResting electrocardiogram (ECG) with corrected QT interval (QTc) > 470 msec on 2 or more time points within a 24-hour period or family history of long QT syndrome.Xx_NEWLINE_xXProlongation of QTc interval to >480 milliseconds (ms)Xx_NEWLINE_xXResting electrocardiogram (ECG) with corrected QT interval (QTc) > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndromeXx_NEWLINE_xXHistory of non-pharmacologically induced prolonged QTc interval >480 milliseconds.Xx_NEWLINE_xXQT interval corrected for rate (QTc) > 480 msec for on the ECG obtained at Screening using Fridericia method for QTc calculationXx_NEWLINE_xXOngoing symptomatic cardiac dysrhythmias, uncontrolled atrial fibrillation, or prolongation of the corrected QT interval defined as > 450 msec for males and > 470 msec for femaleXx_NEWLINE_xXCorrected QT interval using Fridericia's formula (QTcF) interval of > 450 msec at study entry; congenital long QT syndromeXx_NEWLINE_xXCorrected QT (QTc) interval (Fridericia formula) > 450 msec for men or > 470 msec for women at study entry; history of congenital long QT syndromeXx_NEWLINE_xXCorrected QT (QTc) interval =< 450 msecXx_NEWLINE_xXPatients with resting corrected QT interval (specifically QTc calculated using the Fridericia formula [QTcF]) > 470 msec from a single electrocardiogram (ECG) performed at study entry or congenital long QT syndrome.Xx_NEWLINE_xXCorrected QT (QTc) interval > 480 msec (based on the mean value of the triplicate electrocardiography [ECG]s), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes.Xx_NEWLINE_xXProlongation of QT interval (QT)/corrected QT interval (QTc) (QTc interval > 470 ms) using the Fridericia method of QTc analysisXx_NEWLINE_xXCorrected QT (QTc) interval prolongation greater than 500 msXx_NEWLINE_xXMean corrected QT interval (QTc) > 450 ms for males or > 470 msec for females calculated from 3 electrocardiograms (ECGs) using Fridericia's formula (within at least 15 minutes, at least 5 minutes apart)Xx_NEWLINE_xXCorrected QT interval by Fridericia's formula (QTcF) > 500 msec within 1 month before the first dose of study treatment\r\n* Three electrocardiography (ECG)s must be performed for eligibility determination; if the average of these three consecutive results for QTcF is =< 500 msec, the subject meets eligibility in this regardXx_NEWLINE_xXStandard 12-lead electrocardiogram (ECG) with the following parameters at screening (defined as the mean of the triplicate ECGs):\r\n* QT corrected by Fridericia's formula (QTcF) interval at screening < 450msec (using Fridericia’s correction)Xx_NEWLINE_xXPatients with prolonged corrected QT(QTc) interval defined as male > 450 msec and female > 470 msecXx_NEWLINE_xXPatients who are on treatment with drugs known to prolong the QT/QTc interval.Xx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >/= 470 ms calculated from 3 electrocardiogram (ECGs) using Fredericia’s CorrectionXx_NEWLINE_xXBaseline QT Fridericia's correction formula (QTcF) ? 470 msecXx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from electrocardiogram (ECG) using Fridericia’s correction by manual read.Xx_NEWLINE_xXFor screening electrocardiographs (ECGs), exclude patients with a Fridericia's corrected QT interval (QTcF) > 480 ms, or JTc > 340 ms for those with an intraventricular conduction delay. If the screening ECG has a QTcF > 480 ms, eligibility can be confirmed if the average of 3 ECGs done 5 minutes apart have an average QTcF < 480 msXx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia’s correctionXx_NEWLINE_xXFridericia's correction formula (QTcF) interval on standard 12-lead electrocardiography (ECG) parameters at screening (defined as the mean of the triplicate ECGs) of < 450 msec for males and < 470 msec for femalesXx_NEWLINE_xXCorrected QT interval (QTc) prolongation > 480 msec, as calculated by either the Bazett or Fridericia formula, as per institutional standardXx_NEWLINE_xXA QT interval corrected for heart rate using the Fridericia’s formula (QTcF) >= 470 msec on screening examXx_NEWLINE_xXFridericia's correction formula (QTcF) > 470 msec on screening electrocardiography (ECG) or congenital long QT syndromeXx_NEWLINE_xXResting electrocardiography (ECG) with correct QT interval (QTc) > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.Xx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s correctionXx_NEWLINE_xXPatient has a QT interval adjusted by the Fridericia formula (QTcF) > 480 msec on screening electrocardiogram (ECG).Xx_NEWLINE_xXHistory of cardiac disease (arrhythmia, conduction abnormality, congenital prolonged QT syndrome, or prolonged corrected QT [QTc] rhythm noted during initial electrocardiogram [EKG] > 480 ms)Xx_NEWLINE_xXCorrected QT (QTC) by 12 lead electrocardiography (EKG) < 450 msecsXx_NEWLINE_xXCorrected QT (QTc) interval > 470 msec (females) or > 450 msec (males)Xx_NEWLINE_xXQT interval adjusted according to Fredericia (QTcF) > 480 msec on screening electrocardiogram (ECG)Xx_NEWLINE_xXPatients who have a mean corrected QT (QTc) interval > 450 ms at base line will be excluded; concomitant use of agents that prolong the QT interval will be avoidedXx_NEWLINE_xXImpaired cardiac function including any one 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 (< 50 beats per minute)\r\n* QTc > 450 msec on baseline ECG; if QTc > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc\r\n* Myocardial infarction within 12 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 or atrial tachyarrhythmiasXx_NEWLINE_xXObtained =< 7 days prior to registration: Corrected QT (QTc) interval =< 500 msec on the baseline electrocardiogramXx_NEWLINE_xXCorrected QT (QTc) interval =< 480 millisecondsXx_NEWLINE_xXCorrected QT (QTc) interval > 480 msec on baseline electrocardiogram (EKG)Xx_NEWLINE_xXDocumented history of prolonged QTc interval =< 6 months prior to registrationXx_NEWLINE_xXElectrocardiogram (ECG) corrected QT (QTc) =< 450 msecXx_NEWLINE_xXTo be performed within 28 days prior to day 1 of protocol therapy: Corrected QT (QTc) interval =< 480 ms (12 lead-electrocardiography [ECG])Xx_NEWLINE_xXQTcF interval ?450 msec using the mean of triplicate electrocardiograms (ECGs).Xx_NEWLINE_xXCorrected QT interval (QTc) =< 470 msec (based on average of screening triplicates)Xx_NEWLINE_xXQT interval corrected using Fridericia's formula (QTcF) >470 msec or history of prolonged QT syndrome or Torsades de pointes, or familial history of prolonged QT syndrome.Xx_NEWLINE_xXKnown congestive heart failure and/ or a known decreased cardiac ejection fraction of < 45%. A baseline QT interval as corrected by Fridericia's formula (QTcF) > 480 msec, a complete left bundle branch block (defined as a QRS interval ? 120 msec in left bundle branch block form) or an incomplete left bundle branch block.Xx_NEWLINE_xXCorrected QT using Fridericia's formula (QTcF) =< 450 msXx_NEWLINE_xXKnown history of QT/corrected QT (QTc) prolongation or torsades de pointes (TdP); patients who are currently receiving treatment with medication with a known risk to prolong the QT interval or inducing torsades de pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drugsXx_NEWLINE_xXProlonged corrected QT interval (QTc) > 450 milliseconds (ms) at the screening visitXx_NEWLINE_xXClinically significant active cardiovascular disease or history of prolonged QT interval corrected for heart rate (QTc)Xx_NEWLINE_xXCorrected QC interval calculated using Fridericia's formula (QTcF) =< 500 msec; ONLY APPLICABLE for patients with NF2 mutation (GSK2256098)Xx_NEWLINE_xXThe subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms =< 7 days before the first dose of study treatmentXx_NEWLINE_xXSubjects must have normal corrected QT interval (QTc) =< 470 msec (based on average of screening triplicates)Xx_NEWLINE_xXBaseline electrocardiogram (EKG) shows normal corrected QT interval (QTc) interval of =< 470 milliseconds (ms)Xx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiography (ECG)s using Frediricia’s correctionXx_NEWLINE_xXCorrected QT (QTc) interval > 450 ms on screening 12-lead electrocardiogram (ECG)\r\n* If baseline QTc on screening ECG meets exclusion criteria:\r\n** Check calcium, potassium, and magnesium serum levels\r\n** Correct any identified hypocalcemia, hypokalemia, and/or hypomagnesemia and repeat ECG to confirm exclusion of patient due to prolonged QTc interval\r\n* For patients with heart rate (HR) 60-100 beats per minute (bpm), manual read of QTc is not required\r\n* For patients with a baseline HR < 60 bpm or > 100 bpm, manual read of the QT interval by a cardiologist is required, with Fridericia correction applied to determine QTc (ie, QTcF)Xx_NEWLINE_xXMean QT interval corrected for heart rate (corrected QT [QTc]) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Bazett’s correctionXx_NEWLINE_xXCardiac ejection fraction >= 50%, and Fridericia's formula corrected QT (QTcF) < 450 ms (male) or < 470 ms (female) on electrocardiogram (ECG) at baselineXx_NEWLINE_xXQTc interval >460 msec (males) or >470 msec (females); or repeated demonstration of a QTc interval >450 msec.Xx_NEWLINE_xXThe use of concomitant medications that prolong the QT/QTc interval.Xx_NEWLINE_xXAny of the following cardiac criteria:\r\n* Mean resting corrected QT interval (QTc using Fridericia’s formula [QTcF]) > 470 msec obtained from 3 electrocardiograms \r\n* Congenital or family history of long or short QT syndrome, Brugada syndrome, known history of QTc prolongation or torsades de pointes within 12 months of entering the study\r\n* Abnormal echocardiogram at baseline (left ventricular ejection fraction [LVEF] < 40% and shortening fraction [SF] < 15%)Xx_NEWLINE_xXDOSE ESCALATION COHORT: History or presence of an abnormal electrocardiogram (ECG) which, in the investigator's opinion, is clinically meaningful; screening corrected QT using Fridericia’s formula (QTcF) interval > 480ms is excluded; subjects with left bundle branch block are excludedXx_NEWLINE_xXHas a QT interval corrected by Fridericia's formula (QTcF) =< 450 msecXx_NEWLINE_xXResting electrocardiogram (ECG) with corrected QT interval (QTc) > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndromeXx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Bazett's formulaXx_NEWLINE_xXCorrected QT (using Bazett's formula [QTcB]) interval < 500 msecsXx_NEWLINE_xXPatients with a mean QT interval corrected by Bazett's formula (QTcB) > 450 msec in males and > 470 msec in femalesXx_NEWLINE_xXAt screening QT interval corrected by Fridericia's formula (QTcF) >= 450 msecXx_NEWLINE_xXPatients with baseline corrected QT (QTc) > 450 ms or patients who are taking medications that prolong the QTc interval at the time of screeningXx_NEWLINE_xXPatients with mean QTc interval >450 msec at screening and patients taking drugs known to prolong the QTc interval (see Section 9, Appendix D) who cannot be switched to an alternative drugXx_NEWLINE_xXProlonged QT interval (corrected QT interval [QTc] > 480 milliseconds) on screening electrocardiogram (EKG) or congenital long QT syndromeXx_NEWLINE_xXThe subject has a corrected QT interval (QTc) > 500 ms at screening or has a history of long QT syndromeXx_NEWLINE_xXBaseline corrected QT (QTc) interval > 500 msecXx_NEWLINE_xXWithin 30 days of registration: Corrected QT interval (QTc) must be < 450 ms in males and < 470 ms in femalesXx_NEWLINE_xXEvidence of corrected QT (QTc) prolongation as defined as QTc using Fredericia's formula (QTcF) > 470 ms (per Fridericia’s formula)Xx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s CorrectionXx_NEWLINE_xXSubjects with baseline QTc interval >470 msec at screeningXx_NEWLINE_xXClinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's\n             method (QTCF) greater than 450 msecXx_NEWLINE_xXInability to measure QT interval on ECGXx_NEWLINE_xXCorrected QT interval (QTc) =< 480 msec per Fridericia’s formula AND PR interval =< 200 msec (using 12-lead electrocardiography [EKG])Xx_NEWLINE_xXBaseline corrected QT interval (QTc) =< 480 msXx_NEWLINE_xXCorrected QT interval less than 500 milliseconds by electrocardiogram (EKG)Xx_NEWLINE_xXPatients must not have a mean resting corrected QT interval (QTc) > 450 msec obtained from 3 consecutive electrocardiograms (ECGs); performed within 28 days prior to sub-study registration; patients must not have any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block); patients must not have any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of ageXx_NEWLINE_xXPatients must not be planning to receive any concomitant medication known to prolong QT intervalXx_NEWLINE_xXPatients must not have a mean resting corrected QT interval (QTc) > 450 msec obtained from 3 consecutive electrocardiograms (ECGs); performed within 28 days prior to Step 2 re-registration; patients must not have any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block); patients must not have any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of ageXx_NEWLINE_xXSubjects who have a corrected QT (Fridericia's correction formula [QTcF]) interval > 480 milliseconds (ms) (CTCAE grade > 1) determined by the electrocardiogram (ECG) recorder’s algorithm on the screening ECGXx_NEWLINE_xXPatients must not have a screening corrected QT Fridericia’s formula (QTcF) interval > 480 msec based on the average of the triplicate electrocardiograms (EKGs) performed within 28 days prior to registration; NOTE: triplicate EKGs are required at other timepoints; patients must not have any family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or torsade de pointesXx_NEWLINE_xXAveraged corrected QT interval (QTc) baseline in 3 electrocardiography (ECG)s at least 5 minutes apart of >= 450 msXx_NEWLINE_xXSevere conduction abnormality including significant corrected QT (QTc) prolongation > 450 msXx_NEWLINE_xXOn screening, inability to determine the Fridericia corrected QT interval (QTcF) interval on the ECG (i.e.: unreadable or not interpretable) or QTcF > 450 msec (using Fridericia’s correction); all as determined by screening ECG (mean of triplicate ECGs)Xx_NEWLINE_xXCorrected QT using the Fridericia formula (QTcF) < 470 msecXx_NEWLINE_xXSubject has a corrected QT by the Fridericia formula (QTcF) > 480 msec on the screening electrocardiogram (ECG) (using the QTcF formula)Xx_NEWLINE_xXCorrected QT (QTc) =< 480 msec\r\n* Note: patients with grade 1 prolonged QTc (450-480 msec) at the time of study enrollment should have correctable causes of prolonged QTc addressed if possible (i.e. electrolytes, medications)Xx_NEWLINE_xXPatients with congenital long QT syndrome, bradyarrhythmias, or QTc > 480 msec are not eligibleXx_NEWLINE_xXQT interval adjusted according to Fridericia (QTcF) > 480 msec on screening electrocardiography (ECG)Xx_NEWLINE_xXQT interval corrected by Fridericia's formula (QTcF) > 450 msec on screening electrocardiogram (ECG)Xx_NEWLINE_xXCorrected QT (QTc) interval on electrocardiogram must be =< 480 msec (Fridericia correction)Xx_NEWLINE_xXProlonged corrected QT interval (QTc) on pre-entry electrocardiogram (> 470 msec for men and > 480 msec for women per American Heart Association (AHA)/American College of Cardiology (ACC) 2011 scientific statementXx_NEWLINE_xXMarked baseline prolongation of QT/QT corrected (QTc) interval (e.g. demonstration of a QTc interval greater than 500 milliseconds)Xx_NEWLINE_xXA prolonged QTc of >= 480 ms interval on electrocardiogramXx_NEWLINE_xXA corrected QT interval calculated by the Fridericia formula (QTcF) =< 500 ms within 28 days before randomization; Note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =< 500 ms, the patient meets eligibility in this regardXx_NEWLINE_xXPatients with a history of prolonged corrected QT (QTc) syndromeXx_NEWLINE_xXPatients with a known history of a prolonged QT interval (corrected QT interval [QTc] > 480) may not be enrolled in this studyXx_NEWLINE_xXPatients may not have any clinically significant cardiovascular disease including the following:\r\n* Myocardial infarction or ventricular tachyarrhythmia within 6 months\r\n* Prolonged corrected QT (QTc) > 480 msec (Fridericia correction)\r\n* Known ejection faction less than institutional normal\r\n* Major conduction abnormality (unless a cardiac pacemaker is present)Xx_NEWLINE_xXAt screening, patients must have no known history of congenital long QT syndrome and must have a corrected mean QTc interval =< 450 msec at baselineXx_NEWLINE_xXCorrected QT interval (QTc) greater than 460 ms at baselineXx_NEWLINE_xXCorrected QT interval (QTc) =< 480 msecXx_NEWLINE_xXCorrected QT interval (QTc) >= 480 msec and/or receiving any concomitant medications that are associated with a risk of QTc prolongation and/or torsades de pointes; NOTE: these medications should be discontinued or replaced with drugs that do not carry these risksXx_NEWLINE_xXPatients with corrected QT interval (QTc) prolongation greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 (> 480 msec); in addition, patients should not be receiving non-study medications known to prolong QTcXx_NEWLINE_xXQT interval corrected for Fridericia formula (QTcF) at screening > 470 msecXx_NEWLINE_xXConcomitant medication(s) known to increase the QT intervalXx_NEWLINE_xXDocumentation of the patient’s history of corrected QT interval (QTc) prolongation, family history of prolonged QTc, and relevant cardiac disease within 10 days prior to registrationXx_NEWLINE_xXQTc prolongation defined as a QTc interval >= 480 msecs or other significant electrocardiogram (EKG) abnormalities are ineligible; Note: if unsure about EKG abnormality, the treating physician should discuss this with Drs. Sherman or BibleXx_NEWLINE_xXPatients must have corrected QT (QTc) interval < 500 msec on baseline electrocardiogram (EKG)Xx_NEWLINE_xXPatient must have an electrocardiogram (ECG) performed within 42 days prior to registration; patient must not have mean corrected QT (QTc) > 500 msec (with Bazett’s correction) in screening electrocardiogram, or other significant ECG abnormality, New York Heart Association (NYHA) classification III or IV; patient must not require concurrent use of drugs or biologics with proarrhythmic potentialXx_NEWLINE_xXProlonged corrected QT interval (QTC) on electrocardiogram (EKG)Xx_NEWLINE_xXProlonged QTCXx_NEWLINE_xXCorrected QT interval (QTc) =< 480 msecXx_NEWLINE_xXSignificant abnormalities on ECG at screening. QTcF >450 msec for males or >470 msec for females at screeningXx_NEWLINE_xXSubjects with mean of triplicate Fridericia-corrected QT interval (QTcF) > 450 ms at Screening based on central reading.Xx_NEWLINE_xXHas a QT interval corrected by Fridericia's formula (QTcF) ?450 msecXx_NEWLINE_xXHas clinically active heart disease including prolonged corrected QT intervalXx_NEWLINE_xXPatient must have a corrected QT interval (QTc) interval < 461 msec on the 12 lead electrocardiogram (ECG) within 42 days prior to registration, patients with asymptomatic or incidental bundle branch blocks may have QTc measured by a cardiologist or standard formulas such as Bazett’s or Fridericia’s to adjust for pre-existing blocksXx_NEWLINE_xXQTc > 470 msec (including subjects on medication);Xx_NEWLINE_xXA QTc interval of >470 msec by the Fridericia formula (QTcF), at the Screening ECG. If the subject's QTcF is >470 msec on the initial ECG, a total of 3 ECGs should be obtained at least 3 minutes apart and all within 30 minutes. The average of the 3 QTcF's will be used to determine eligibility. Known or suspected causes of prolonged QTc can be treated (e.g., hypocalcemia, hypokalemia, hypomagnesimia) and the ECGs may be repeated. If the subject initiates treatment with a drug known to prolong the QTc during the Screening period after the initial Screening ECGs were obtained, the Screening ECGs must be repeated once the new drug has reached steady state to ensure the average QTcF remains ?470 msec. For subject's whose heart rate is <60 bpm, the Bazett correction formula (QTcB) may be used.Xx_NEWLINE_xXSubjects with a QTcF interval of >470 msec; if the Screening ECG QTcF interval is >470 msec, it may be repeated, and if repeat <470 msec, the subject may be enrolled.Xx_NEWLINE_xXSubjects with heart-rate corrected QT (QTc) interval ?450 ms or other factors that increase the risk of QT prolongation or arrhythmic events.Xx_NEWLINE_xXPatients taking medications that are known to prolong the QT intervalXx_NEWLINE_xXQTcF interval < 450 msec and mean resting heart rate 50-90 bpmXx_NEWLINE_xXAny concomitant medications that are associated with a risk of corrected QT interval (QTc) prolongation and/or torsades de pointes should be discontinued or replaced with drugs that do not carry these risks, if possible; patients who must take medication with a risk of possible risk of torsades de pointes should be watched carefully for symptoms of QTc prolongation, such as syncope; patients with personal or family history of congenital long QTc syndrome are NOT eligibleXx_NEWLINE_xXHeart-rate corrected QT interval (QTc) prolongation > 470 msec at screeningXx_NEWLINE_xXPatients with QTc interval ?450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome)Xx_NEWLINE_xXFor participants receiving alectinib: baseline Fridericias corrected QT interval (QTcF) greater than (>) 470 milliseconds (ms) or symptomatic bradycardia.Xx_NEWLINE_xXMean resting corrected QT interval (QTc) calculated using Fridericia's formula (QTcF) >450 msec obtained from 3 electrocardiograms (ECGs); family or personal history of long or short QT syndrome; Brugada syndrome or known history of QTc prolongation or torsade de pointes within 12 months of the subject entering the study.Xx_NEWLINE_xXCongenital long QT syndrome or a corrected QT interval (QTc) ?450 ms at Screening (unless secondary to pacemaker or bundle branch block).Xx_NEWLINE_xXCorrected QT interval (QTc) > 480 milliseconds as corrected by the Fridericia formulaXx_NEWLINE_xXScreening 12-lead ECG with measurable QTc interval (according to either Fridericia's or Bazett's correction) of >=470 msec).Xx_NEWLINE_xXMean resting corrected QT interval (QTc using Fridericia’s formula [QTcF]) > 470 msecXx_NEWLINE_xXQTc interval >0.450 seconds (males) or >0.470 (females), or known history of QTc prolongation or Torsade de Pointes (TdP)Xx_NEWLINE_xXCorrected QT interval (QTc) > 480 miliseconds (msecs)Xx_NEWLINE_xXBaseline corrected QT interval (QTc) < 480 msXx_NEWLINE_xXCorrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before start of treatment; Note: at baseline (i.e. screening), three ECGs to be obtained within 30 minutes but approximately 2 to 3 minutes apart (i.e. triplicate); if the average of the three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regardXx_NEWLINE_xXPatients who have a mean resting correct corrected QT (QTc) interval using the Fridericia formula (QTcF) > 470 msec (as calculated per institutional standards) obtained from 3 electrocardiograms (ECGs) 2-5 minutes apart at study entry, or congenital long QT syndrome; AZD1775 should not be given to patients who have a history of Torsades de pointes unless all risk factors contributed to Torsades have been corrected; AZD1775 has not been studied in patients with ventricular arrhythmias or recent myocardial infarctionXx_NEWLINE_xXHas a QTc prolongation to > 450 millisecond (ms) in males and > 470 ms in femalesXx_NEWLINE_xXPatients who require use of a concomitant medication that can prolong the QT intervalXx_NEWLINE_xXPatients with baseline QTc > 480 msec.Xx_NEWLINE_xXQTc >480 msecXx_NEWLINE_xXHas marked prolongation of QTc(F) interval at screening or baseline (QTc[F] interval > 470 msec) using the Fridericia method of correction for heart rate.Xx_NEWLINE_xXA clinically significant electrocardiogram (ECG) abnormality, including a marked Baseline prolonged QT/QTc interval (e.g., a repeated demonstration of a QTc interval >500 milliseconds (msec)).Xx_NEWLINE_xXHistory of long QT syndrome or whose corrected QT interval (QTc) measured (Fridericia method) at screening is prolonged (> 450 ms).Xx_NEWLINE_xXHistory of prolonged QTc interval (e.g., repeated demonstration of a QTc interval > 450 milliseconds).Xx_NEWLINE_xXCardiac function: baseline corrected QT (QTc) interval =< 450 msecsXx_NEWLINE_xXBaseline cardiac QTc interval > 450 msecsXx_NEWLINE_xXHas a QT interval corrected by Fridericia's formula (QTcF) ?480 msecXx_NEWLINE_xXHas QT interval corrected for heart rate (QTc) ?480 msec.Xx_NEWLINE_xXInability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF > 450 msec (using Fridericia’s correction); NOTE: all as determined by screening ECGXx_NEWLINE_xXHas marked prolongation of QTc(F) interval at screening or baseline (QTc[F] interval > 470 msec) using the Fridericia method of correction for heart rateXx_NEWLINE_xXA baseline ECG QTcF > 470 msecXx_NEWLINE_xXHas a QT interval corrected by Fridericia's formula (QTcF) less than or equal to (<=) 480 milliseconds (msec)Xx_NEWLINE_xXCorrected QT interval duration prolongationXx_NEWLINE_xXAny of the following ECG findings: Baseline QTcF interval >=450 millisecond (msec); Any clinically significant ECG assessments should be reviewed by the site cardiologist prior to study entry.Xx_NEWLINE_xXHas a QT interval corrected by Fridericia's formula (QTcF) ?480 msecXx_NEWLINE_xXHave normal QT interval on screening ECG evaluation, defined as QT interval corrected (Fridericia) (QTcF) of ?450 milliseconds (msec) in males or ?470 msec in females.Xx_NEWLINE_xXCongenital long QT syndrome or a corrected QTc interval ?450 ms at the Screening visit.Xx_NEWLINE_xXElectrocardiogram (ECG) showing clinically significant abnormality at Screening or showing an average QTc interval ?450 msec in males and ?470 msec in females (?480 msec for subjects with Bundle Branch Block (BBB) over 3 consecutive ECGs).Xx_NEWLINE_xXNo marked baseline prolongation of QT/QTc intervalXx_NEWLINE_xXCorrected QT interval > 480 msec (using the Fridericia formula)Xx_NEWLINE_xXSubjects with mean QTcF interval > 500 ms.Xx_NEWLINE_xXHave chronic atrial fibrillation or QTc interval corrected for heart rate of greater than 470 msec in adults and 450 msec in pediatrics (< 18 years).Xx_NEWLINE_xXQTc interval of > 480 ms.Xx_NEWLINE_xXQTcF > 470 msec on the screening ECGXx_NEWLINE_xX12 lead ECG with QtcF interval ? 470 msecXx_NEWLINE_xXQTcF interval at screening < 450 msec (using Fridericia's correction).Xx_NEWLINE_xXCorrected QT interval (QTc) > 500 ms at baseline (average of 3 determinations at 10 minutes interval)Xx_NEWLINE_xXPatients with a baseline electrocardiography (ECG) demonstrating a corrected QT (QTc) > 460 msXx_NEWLINE_xXHistory of long QT syndrome or whose corrected QT interval (QTc) measured (Fridericia method) at screening is prolonged (> 470 ms). Individuals who screen fail due to this criterion are not eligible to be re-screenedXx_NEWLINE_xXPatients with prolonged corrected QT (QTc) interval (> 500 msec) determined by electrocardiogram (EKG) within 28 days prior to registrationXx_NEWLINE_xXhistory or family history of long QT syndrome; 12-Lead electrocardiogram (ECG) abnormalities considered by the investigator to be clinically significant or QTcF ? 450 milliseconds, regardless of clinical significance, at screening. Abnormal ECG may be confirmed with one repeat assessment. For subjects with QTcF ? 450 msec on initial ECG, the mean of the two QTcF assessments will determine eligibility;Xx_NEWLINE_xXIncreased corrected QT (QTc) interval (QTc > 470 ms), patients with baseline resting bradycardia < 45 beats per minute (bpm), or baseline resting tachycardia > 100 bpmXx_NEWLINE_xXFamily history of long QT syndrome or other risk factors for torsades de pointes, and/or the use of concomitant medications that prolong the QT/QTc intervalXx_NEWLINE_xXBaseline prolongation of the rate-corrected QT interval (QTc; example, repeated demonstration of QTc interval >480 millisecond [ms], or history of congenital, long-QT syndrome, or torsades de pointes).Xx_NEWLINE_xXHave a corrected QT interval >470 milliseconds as calculated be the Fredericia equation.Xx_NEWLINE_xXA clinically significant electrocardiogram (ECG) abnormality (ie, corrected QT interval [QTc] interval greater than 480 msec when electrolyte balance is normal), or a history of risk factors for torsade de pointes, hypokalemia, long QT syndrome, or the use of concomitant medications resulting in a prolongation of QTc interval.Xx_NEWLINE_xXMean QT interval corrected for heart rate (corrected QT [QTc]) < 470 msec calculated from 3 electrocardiograms (ECGs) performed at least 2 minutes apart using Fridericia’s correctionXx_NEWLINE_xXInability to determine the QTcF interval on the ECG (i.e. unreadable or not interpretable) or QTcF > 450 msec (using Fridericia's correction). All as determined by screening ECG (using the mean QTcF of triplicate ECGs)Xx_NEWLINE_xXMedications that have a known risk to prolong the QT interval or induce Torsades de PointesXx_NEWLINE_xXMean resting corrected QT interval (QTc) ?450 msec for males and ?470 msec for females.Xx_NEWLINE_xXKnown history or predisposition to QT interval prolongationXx_NEWLINE_xXCorrected QT interval (QTc) =< 500 milliseconds (ms)Xx_NEWLINE_xXThat have a known risk to prolong the QT interval or induce Torsades de Pointes.Xx_NEWLINE_xXProlongation of QT/QTc intervalXx_NEWLINE_xXElectrocardiogram (ECG) demonstrating clinically significant arrhythmias (Note: participants with chronic atrial arrhythmia, ie, atrial fibrillation or paroxysmal supraventricular tachycardia, are eligible). A clinically significant ECG abnormality, including a marked prolonged QT/QTc interval (eg, a repeated demonstration of a QTc interval of greater than 500 ms).Xx_NEWLINE_xXEvidence of QTcF prolongation defined as > 450 ms for males and > 470 ms for females at screeningXx_NEWLINE_xXClinically significant ECG abnormalities or any factors that increase the risk of corrected QT interval prolongation or risk of arrhythmic eventsXx_NEWLINE_xXFridericia´s Corrected QT interval (QTcF) prolongation > 450 ms or QT prolongation deemed clinically relevant by the investigator (e.g., congenital long QT syndrome). The QTcF will be calculated as the mean of the 3 ECGs taken at screening.Xx_NEWLINE_xXPatients must have corrected QT (QTc) =< 500 msecXx_NEWLINE_xXCorrected QT interval (QTc) > 470 msec; excluded are patients who may develop prolongation of QTc; these conditions include patients with hypokalemia or hypomagnesemia, patients with congenital long QT syndrome, patients taking anti-arrhythmic medicines or other medicinal products that lead to QT prolongation, and cumulative high-dose anthracycline therapyXx_NEWLINE_xXCorrected QT interval (QTc) < 480 msecXx_NEWLINE_xXCorrected QT (QTc) interval > 500 msec; if QTc interval is > 500 msec, then 2 additional electrocardiograms (ECGs) should be obtained over a brief period of time (e.g., within 15-20 minutes) to confirm the abnormality; the average QTc interval will be determined from the 3 ECG tracings by manual evaluation and will be used to determine if the subject will be excluded from the study; the same method of QTc determination must be used throughout the subject’s participation in the trialXx_NEWLINE_xXScreening QTcF >450 msec or current medication known to prolong QTXx_NEWLINE_xXParts A, B, C, and E: Have QTc interval of > 470 millisecond (msec) on screening electrocardiogram (ECG). Part D participants have QTc interval of >450msec on screening ECG. Additional Exclusion Criteria For Part CXx_NEWLINE_xXA baseline QT interval as corrected by Fridericia's formula (QTcF) > 450 msec, a complete left bundle branch block (defined as a QRS interval ? 120 msec in left bundle branch block form) or an incomplete left bundle branch block.Xx_NEWLINE_xXProlonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 450 msec) within 30 days prior to study registrationXx_NEWLINE_xXCorrected QTc interval > 480 msec; baseline electrocardiogram (EKG) obtained pre-transplant does not need to be repeated unless clinically indicatedXx_NEWLINE_xXProlongation of QTc interval to greater than 480 msXx_NEWLINE_xXThe subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before treatment initiationXx_NEWLINE_xXImpaired cardiac function including any of the following:\r\n* Congenital long QT syndrome or a known family history of long QT syndrome\r\n* History or presence of clinically significant ventricular or atrial tachyarrhythmias\r\n* Clinically significant resting bradycardia (< 50 beats per minute)\r\n* Inability to monitor the QT interval by electrocardiogram (ECG)\r\n* Corrected QT (QTc) > 450 msec on baseline ECG; if QTc > 450 and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc\r\n* Myocardial infarction within 1 year of starting study drug\r\n* Other clinically significant heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension)Xx_NEWLINE_xXQTcF prolongation (defined as a QTcF > 450 msec)Xx_NEWLINE_xXTreatment with medications known to cause corrected QT (QTc) interval prolongation within 7 days of study day 1 is not permitted unless approved by the sponsor; use of ondansetron is permitted for treatment of nausea and vomitingXx_NEWLINE_xXPatients with a baseline QTc > 500 msec and patients with a family history of prolonged QT syndromeXx_NEWLINE_xXQTcF >450 msec (males) or >470 msec (females).Xx_NEWLINE_xXClinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolonged QT/corrected QT (QTc) ([QT interval/corrected QT interval], e.g., a repeated demonstration of a QTc interval > 480 ms), a family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or torsade de pointes (TdP)Xx_NEWLINE_xXSubject with mean Fridericia-corrected QT interval (QTcF) > 450 ms at screening based on central reading.Xx_NEWLINE_xXOn screening, inability to determine the Fridericia's corrected QT (QTcF) interval on the ECG (i.e.: unreadable or not interpretable) or QTcF> 450 msec (using Fridericia’s correction); all as determined by screening ECGXx_NEWLINE_xXConcurrent use of digoxin due to cardiac disease; corrected QT (QTc) interval >= 450 milliseconds in men and >= 470 milliseconds in women within 2 weeks of registration or known history of QTc prolongation or Torsades de PointesXx_NEWLINE_xXQTcF >470 msec on screening ECG or congenital long QT syndromeXx_NEWLINE_xXA screening Fridericia corrected QT interval (QTcF) >= 450 ms (men) or >= 470 ms (women)Xx_NEWLINE_xXQTc <450 msec on screening ECG.Xx_NEWLINE_xXPatient with available standard 12-lead electrocardiography (ECG) with the following parameters at screening: a. Corrected QT interval by Fridericia's formula (QTcF) interval at screening < 450 msec (using Fridericia’s correction). b. Resting heart rate 50-100 beats per minute (bpm).Xx_NEWLINE_xXCorrected QT using Fridericia's correction formula (QTcF) =< 480 msecXx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's correctionXx_NEWLINE_xXMean resting corrected QT interval (QTc), calculated using Fridericia’s formula, > 470 msec obtained from 3 electrocardiograms (ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes within 12 months of the patient entering in the studyXx_NEWLINE_xXCorrected QT interval using Fridericia’s formula (QTcF) value > 480 msec at screening; family or personal history of long corrected QT (QTc) syndrome or ventricular arrhythmias including ventricular bigeminy at screening; previous history of drug-induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on electrocardiogram (ECG)Xx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s correctionXx_NEWLINE_xXCorrected QT interval (QTc) > 470 milliseconds (msec) on a 12-lead electrocardiography (EKG) obtained during the screening period; if a machine reading is above this value, the EKG should be reviewed by a qualified reader and confirmed on a subsequent EKGXx_NEWLINE_xXQTc interval ? 470 msec at BaselineXx_NEWLINE_xXImpaired 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 (< 50 beats per minute)\r\n* Corrected QT (QTc) > 450 msec on baseline ECG; NOTE: if the ECG shows a QTc interval greater than 450 msecs at screening triplicates should be performed, one minute apart to confirm the finding (after replacement of any electrolyte imbalance); if 2/3 or 3/3 of the ECGs confirm the QT prolongation (i.e. QTc interval > 450 msecs) the patient must not be included into the trial\r\n* Myocardial infarction =< 3 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 < 45%\r\n* History of congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXMean QT interval ?470 msXx_NEWLINE_xXMean QT interval corrected for heart rate (corrected QT [QTc]) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Frederica’s CorrectionXx_NEWLINE_xXThe calculated Fridericia's corrected QT interval (QTcF) average of the triplicate electrocardiograms (ECGs) must be < 470 msecXx_NEWLINE_xXHistory of prolonged QT syndrome or electrocardiogram (ECG) at screening QT interval corrected for heart rate (QTc) of > 470 ms with Bazett’s or Fridericia’s formulaXx_NEWLINE_xXAbnormalities on 12-lead electrocardiogram (ECG) considered by the investigator to be clinically significant or baseline prolongation of the rate-corrected QT interval (e.g., repeated demonstration of QTc interval > 480 milliseconds).Xx_NEWLINE_xXThe participant has a QT interval calculated using Bazett's formula (QTcB) interval of >450 milliseconds (msec) for males and >470 msec for females on screening electrocardiogram (ECG).Xx_NEWLINE_xXBaseline corrected QT interval (QTc) =< 480 milliseconds (ms)Xx_NEWLINE_xXCurrent use of drugs that are known to prolong the QT intervalXx_NEWLINE_xXImpaired 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 12 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 50% 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 12 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 > 450 msec (using Fridericia’s correction); all as determined by screening ECG (mean of triplicate ECGs)Xx_NEWLINE_xXMean resting corrected QT interval (Fridericia formula for QT interval correction [QTcF]) > 480 msec obtained from 3 electrocardiograms (ECGs)Xx_NEWLINE_xXCorrected QT interval using Fridericia's formula (QTcF) > 470 msec within 4 weeks of enrollment; if the initial QTcF is found to be > 470 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =< 470 ms, the subject meets eligibility in this regardXx_NEWLINE_xXBaseline screening corrected QT (QTc) < 470 ms is eligibleXx_NEWLINE_xXHave Fridericia-corrected QT interval (QTcF) > 470 msec (female) or > 450 (male), or history of congenital long QT syndrome.Xx_NEWLINE_xXA screening Fridericia corrected QT interval (QTcF) ? 450 ms (men) or ? 470 ms (women).Xx_NEWLINE_xXPatient must have a corrected QT (QTc) interval on electrocardiogram (ECG) =< 0.48 seconds by Bazett’s calculation at screeningXx_NEWLINE_xXPatients with Common Terminology Criteria for Adverse Events (CTCAE) grade 2 cardiac arrhythmias may be considered for inclusion if the arrhythmias are stable, asymptomatic, and unlikely to affect patient safety; patients will be excluded if they have ongoing cardiac dysrhythmias of CTCAE grade >= 3, corrected QT interval (QTc) prolongation > 450 ms, or other factors that increase the risk for QT interval prolongation (eg, heart failure, hypokalemia [defined as serum potassium < 3.0 mEq/L that is persistent and refractory to correction], or family history of long QT interval syndrome)Xx_NEWLINE_xXCorrected QT interval (QTc)/QT Fridericia equation (QTf) interval >= 480 milliseconds; unless secondary to pacemaker or bundle branch blockXx_NEWLINE_xXPatients taking drugs that can cause significant QTc/QTf prolongation unless able to be switched to non-QTc/QTf prolonging medication or on a stable dose without significant QT prolongation (> 470 msec)Xx_NEWLINE_xXPatient requires the use of concomitant medications that are contraindicated with cardiac glycosides and/or are known to prolong the QT/QTc interval during study participation (see Appendix 2).Xx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) ?470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's CorrectionXx_NEWLINE_xXMean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTcF value.Xx_NEWLINE_xXAny patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval.Xx_NEWLINE_xXQTcF interval at screening >450 msec (using Fridericia's correction)Xx_NEWLINE_xXQT interval corrected (QTc) <450 millisecond (msec) or QTc <480 msec for patients with bundle branch block.Xx_NEWLINE_xXThe QTc is the QT interval corrected for heart rate according to either Bazett's formula (QTcB)Xx_NEWLINE_xXFor purposes of this data analysis, Bazett's formula will be used as the primary method of calculating the corrected QT interval. The QTc should be based on either a single Electrocardiogram (ECG) or an average of 3 sequential ECGs obtained within 24 hours of each other.Xx_NEWLINE_xXPatients who have a resting electrocardiogram (ECG) with a Fridericia corrected QT (QTcF) interval of >= 470 msec at 2 or more time points within a 24 hour period or a family history of long QT syndromeXx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) ?470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's CorrectionXx_NEWLINE_xXOther medications known to prolong QT interval should be discontinued and if not possible, patient is excluded from this studyXx_NEWLINE_xXCorrected QT interval (QTc) =< 480 ms within 14 days before enrollmentXx_NEWLINE_xXBaseline corrected QT interval using Fridericia's formula (QTcF) > 480 ms; NOTE: this criterion does not apply to patients with a left bundle branch blockXx_NEWLINE_xXConcurrent treatment with any agent known to prolong the corrected QT (QTc) intervalXx_NEWLINE_xXPatients will be required to have a baseline electrocardiogram (EKG) prior to the start of treatment; patients with a corrected QT (QTc) > 480 millisecond (ms) are excluded from the studyXx_NEWLINE_xXCorrected QT (QTc) interval >= 450 msec at baseline or history of congenital long QT syndrome or uncorrectable electrolyte abnormalitiesXx_NEWLINE_xXImpaired cardiac function or clinically significant heart disease, including any one of the following: a) angina pectoris within 3 months; b) acute myocardial infarction within 3 months; c) QT interval corrected with the Fridericia formula (QTcF) greater than 450 msec for males and greater than 470 msec for females on the screening electrocardiogram (ECG); d) a past medical history of clinically significant ECG abnormalities or a family history of prolonged QT-interval syndrome; e) other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)Xx_NEWLINE_xXMean resting correct QT interval (QTc) >470 msec obtained from triplicate electrocardiagramsXx_NEWLINE_xXHave normal QT interval on screening electrocardiogram (ECG) evaluation, defined as QT interval corrected (Fridericia) (QTcF) of ?450 ms in males or ?470 ms in females.Xx_NEWLINE_xXSubjects with heart-rate corrected QT (QTc) interval ? 450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome). Subjects with right bundle branch block and a prolonged QTc interval should be reviewed by the Medical Monitor for potential inclusion.Xx_NEWLINE_xXSubjects taking medications that are known to prolong the QT interval (see Section 9.11.3).Xx_NEWLINE_xXScreening ECG QTc interval ?470 msec for females, ?450 msec for males.Xx_NEWLINE_xXAt increased risk for developing prolonged QT interval, including hypokalemia or hypomagnesemia, unless corrected to within normal limits prior to first dose of SNX-5422; congenital long QT syndrome or a history of torsade de pointes; currently receiving anti-arrhythmics or other medications that may be associated with QT prolongation.Xx_NEWLINE_xXGrade 3 corrected QT interval (QTc) prolongation (QTc > 500 msec on two separate electrocardiograms (ECGs)Xx_NEWLINE_xXPatients must have QTc interval less than 450 msecXx_NEWLINE_xXBaseline corrected QT interval (QTc) =< 480 msXx_NEWLINE_xXCurrent use of drugs that are known to prolong the QT intervalXx_NEWLINE_xXPatients must have a baseline electrocardiogram (ECG) showing corrected QT (QTc) interval =< 460 msec within 28 days prior to registrationXx_NEWLINE_xXThe subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 milliseconds (ms) within 28 days before initiation of cabozantinib; Note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regardXx_NEWLINE_xXCorrected QT interval (QTc) > 480 msec; history of QT syndrome, Brugada syndrome or known history of QTc prolongation, or torsade de pointesXx_NEWLINE_xXQT interval corrected for heart rate by Fridericia's formula (QTcF) ? 480msXx_NEWLINE_xXParticipants with a history of congenitally prolonged corrected QT interval (QTc), a first degree relative with unexplained sudden death under 40 years of age, or a measured QTcB (Bazett’s correction) longer than 480 msec on electrocardiogram (ECG); ECGs should be performed after correction of electrolyte abnormalities; participants with a prolonged QTcB should have a repeat ECG twice, at least 24 hour apart, and the average of the 3 QTcBs should not exceed 480 msec; history of QT prolongation associated with other medications that required discontinuation of that medicationXx_NEWLINE_xXSubjects with a corrected QT interval (QTc) > 480 msec (QTc > 510 msec for subjects with bundle branch block) at baselineXx_NEWLINE_xXBaseline QT interval corrected with Fridericia's method (QTcF) > 480 ms (average of triplicate readings) Note: This criterion does not apply to subjects with a right or left bundle branch block (BBB)Xx_NEWLINE_xXNormal corrected QT (QTc) interval defined on electrocardiogram (EKG) as QTc =< 440 msec\r\n* Note: patients who are assigned to arm B must have QTc =< 440 msec on day (D)1 and D8 of cycle 1 of eribulin treatments for continued eligibility\r\nPostmenopausal women defined as women with:\r\n* Prior bilateral surgical oophorectomy, or\r\n* Medically confirmed post-menopausal status defined as spontaneous cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological causeXx_NEWLINE_xXCorrected QT interval using Fridericia's formula (QTcF) value > 480 msec at screening; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy; previous history of drug-induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on electrocardiogram (ECG)Xx_NEWLINE_xXHistory of congenital long QT syndrome or corrected QT interval (QTc) greater than (>) 450 milliseconds at screeningXx_NEWLINE_xXMean resting QTc >470 msec obtained from 3 ECGsXx_NEWLINE_xXConcomitant use of drugs that may cause a prolongation of the QT interval corrected by Fridericia's formula (QTcF) or inducing torsades de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug; if these drugs become medically necessary during study, they must be used with cautionXx_NEWLINE_xXOn screening, any of the following cardiac parameters: bradycardia (heart rate < 50 at rest), tachycardia (heart rate > 90 at rest), PR interval > 220 msec, QRS interval >109 msec, or QTcF >450 msec.Xx_NEWLINE_xXThat have a known risk to prolong the QT interval or induce Torsades de Pointes.Xx_NEWLINE_xXCorrected QT interval (QTc) > 480 msecs using Bazett's formula; electrocardiography (EKG) for screening must be =< 28 days before registrationXx_NEWLINE_xXSubject has Fridericia-corrected QT interval (QTcF) > 450 ms at Screening based on central reading.Xx_NEWLINE_xXSubject has Long corrected QT interval (QTc) Syndrome at Screening.Xx_NEWLINE_xXResting electrocardiogram (ECG) with corrected QT (QTc) > 470 msec on 2 or more time points within a 24 hour period or a documented family history of long QT syndrome.Xx_NEWLINE_xXOn electrocardiogram, corrected QT (QTc) interval > 500 msecXx_NEWLINE_xXCorrected QT (QTc) interval > 450 ms for men or 470 ms for women, or known history of QTc prolongation or Torsades de PointesXx_NEWLINE_xXProlonged rate corrected QT (QTc) interval >= 500 msec, calculated according to institutional guidelinesXx_NEWLINE_xXQT (Interval from the beginning of the QRS complex to the end of the T wave on an electrocardiogram) interval with Fridericia's correction [QTcF] >450 milliseconds. The QTcF should be calculated as the arithmetic mean of the QTcF on triplicate ECGs. In the case of potentially correctible causes of QT prolongation (e.g., medications, hypokalemia), the triplicate ECG may be repeated once during screening and that result may be used to determine eligibility.Xx_NEWLINE_xXPlanned concomitant use of medications known to prolong the QT/QTc intervalXx_NEWLINE_xXParticipant has a corrected QT (QTc) interval > 470 ms or known history of QTc prolongation or Torsade de PointesXx_NEWLINE_xXSubjects with heart-rate corrected QT (QTc) interval ?450 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) at screening.Xx_NEWLINE_xXA baseline corrected QT interval of > 470 msXx_NEWLINE_xXPatients must not have a corrected QT (QTc) interval >= 480 msecs within 28 days prior to registrationXx_NEWLINE_xXHistory of congenital long QT syndrome or a corrected QTc interval >= 450 msec at baselineXx_NEWLINE_xXSubjects with a QTc > 480 msec (QTc > 510 msec for subjects with Bundle Branch Block) at baselineXx_NEWLINE_xXCorrected QT interval (QTc) of > 480 msec using Bazett’s formulaXx_NEWLINE_xXCorrected QT (QTc) prolongation, as defined by > 470 milliseconds on ECGXx_NEWLINE_xXNo ongoing cardiac dysrhythmias, atrial fibrillation, or prolongation of corrected QT (QTc) interval to > 480 msecXx_NEWLINE_xXQTc\t=< 480 msecsXx_NEWLINE_xXPatient has a corrected QT interval (QTcF) > 500 ms at screeningXx_NEWLINE_xXCorrected QT interval (QTc) > 480 msecs\r\n* Note: correction method should be reportedXx_NEWLINE_xXProlongation of corrected QT interval (QTc) > 480 milliseconds using Bazett’s formulaXx_NEWLINE_xXElectrocardiogram (ECG) corrected QT (QTC) interval < 470 msXx_NEWLINE_xXImpaired cardiac function including any one 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 (< 50 beats per minute)\r\n* Corrected QT (QTc) > 450 msec on baseline ECG; if QTc > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc\r\n* Myocardial infarction =< 12 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 < 45%\r\n* History of, congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXAt Screening QTcF ?450 msec for males and ?470 msec for females.Xx_NEWLINE_xXProlonged corrected QT (QTc) interval (>= 450 msec) as calculated by Bazett’s formula, or patients with a history of congenital long QT syndrome or uncorrectable electrolyte abnormalitiesXx_NEWLINE_xXProlonged QTc interval on pre-entry electrocardiogram (>/= 450 msec)Xx_NEWLINE_xXCorrected QT interval corrected for Fridericia's formula (QTcF) < 450 msXx_NEWLINE_xXProlonged corrected QT (QTc) interval (>= 500 msec), as calculated by Bazett's formulaXx_NEWLINE_xXCorrected QT (QTc) interval greater than or equal to 480 msecs (>= 500 msec for subjects with bundle branch block)Xx_NEWLINE_xXCorrected QT interval according to Fridericia (QTcF) prolongation > 470 ms or QT prolongation deemed clinically relevant by the investigator (e.g., congenital long QT syndrome).The QTcF will be calculated as the mean of the 3 Electrocardiogram (ECGs) taken at screening.Xx_NEWLINE_xXCorrected QT interval using Bazett's formula (QTcB) > 470 milliseconds (msec) on a 12-lead electrocardiogram (ECG) obtained during the screening period; if a machine reading is above this value, the ECG should be reviewed by a qualified reader and confirmed on a subsequent ECGXx_NEWLINE_xXCorrected QT interval (QTc) < 480 msecsXx_NEWLINE_xXElectrocardiogram (ECG) without evidence of clinically significant ventricular arrhythmias or ischemia as determined by the investigator and a rate-corrected QT interval (QTc, Bazett's formula) of < 480 msecXx_NEWLINE_xXPatients must have a corrected QT (QTc) interval < 450 ms on baseline electrocardiogram (EKG)Xx_NEWLINE_xXInability to determine the QT interval on ECGXx_NEWLINE_xXQTcF > 480 msecXx_NEWLINE_xXThe subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before initiation of protocol therapy; Note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regardXx_NEWLINE_xXCorrected QT (QTc) interval > 500 msec, unless a bundle branch block is also presentXx_NEWLINE_xXPatient must not have corrected QT (QTc) > 500 ms within 14 days before enrollmentXx_NEWLINE_xXImpaired cardiac function including any of the following:\r\n* Congenital long QT syndrome or a known family history of long QT syndrome;\r\n* History or presence of clinically significant ventricular or atrial tachyarrhythmias\r\n* Clinically significant resting bradycardia (< 50 beats per minute) \r\n* Inability to monitor the QT interval by electrocardiogram (ECG)\r\n* Corrected QT interval (QTc) > 450 msec on baseline ECG; if QTc > 450 and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc\r\n* Myocardial infarction within 1 year of starting study drug\r\n* Other clinically significant heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension)Xx_NEWLINE_xXPatient with corrected QT (QTc) interval must be less than 500 msecXx_NEWLINE_xXThe subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before randomizationXx_NEWLINE_xXPatients must have corrected QT (QTc) < 500 msecXx_NEWLINE_xXPatients with QTc prolongation (defined as a QTc interval equal to or greater than 500 msec) or other significant echocardiogram (ECG) abnormalities are excludedXx_NEWLINE_xXPatients with a baseline corrected QT interval (QTc) > 500 msXx_NEWLINE_xXCorrected QT interval (QTc) > 480 msecs using Bazett’s formulaXx_NEWLINE_xXThe patient has a corrected QT interval (corrected QT using Fridericia formula [QTcF]) > 500 ms within 28 days before randomization; if QTcF is >= 500 ms by Bazett formula, this must be confirmed by the Fridericia formulaXx_NEWLINE_xXCorrected QT interval (QTc) > 475 millisecondsXx_NEWLINE_xXQTcF > 480 msec, family or personal history of long QTc syndrome or ventricular bigeminy; previous history of drug-induced QTc prolongation or the need for medications known or suspected of producing prolonged QTc intervals on ECGXx_NEWLINE_xXCorrected QTc > 470 msec; the corrected QTc may be corrected using either Bazett’s or Fridericia’s formula; in general Fridericia corrected QT interval (QTcf) is the preferred correction methodXx_NEWLINE_xXCorrected QT interval (QTc) > 480 msecs using Bazett’s formulaXx_NEWLINE_xXCorrected QT (QTc) interval > 470 msecXx_NEWLINE_xXCorrected QT interval less than 500 milliseconds by electrocardiogram (EKG)Xx_NEWLINE_xXCorrected QT (QTc) interval =< 470 ms on screening electrocardiogram (ECG)Xx_NEWLINE_xXProlongation of corrected QT interval (QTc) > 480 msecsXx_NEWLINE_xXThe subject has a baseline corrected QT interval < 500 within 28 days before randomizationXx_NEWLINE_xXScreening electrocardiogram (ECG) with a QTcF > 450 millisecond (msec)Xx_NEWLINE_xXSubjects with a baseline corrected QT (QTc) of equal to or greater than 480 msecs or other significant electrocardiogram (ECG) abnormalitiesXx_NEWLINE_xXCorrected QT interval (QTc) > 480 msecs using Bazett’s formulaXx_NEWLINE_xXImpaired cardiac function or clinically significant heart disease, including any one of the following:\r\n* Angina pectoris within 3 months\r\n* Acute myocardial infarction within 3 months\r\n* QT interval corrected using Fridericia’s formula (QTcF) > 450 msec for males and > 470 msec for females on the screening electrocardiogram (ECG)\r\n* A past medical history of clinically significant ECG abnormalities or a family history of prolonged QT-interval syndrome\r\n* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)Xx_NEWLINE_xXFor patients on mefloquine arm, a baseline electrocardiogram (EKG) without evidence of prolonged corrected QT (QTc) interval > 450 ms or clinically significant arrhythmia must be obtained within 14 days prior to registrationXx_NEWLINE_xXFor mefloquine arm, patients with evidence of QTc interval > 450 ms or clinically significant arrhythmia on baseline EKG obtained within 14 days of registration will be ineligible for protocol enrollmentXx_NEWLINE_xXProlongation of corrected QT interval (QTc) > 480 msecsXx_NEWLINE_xXInability to monitor the QT interval on electrocardiogram (ECG)Xx_NEWLINE_xXCorrected QT interval (QTc) (based on Bazett) > 450 msec on baseline ECG; if QTc > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTcXx_NEWLINE_xXCorrected QT (QTc) =< 500 msec on baseline electrocardiogram (ECG)Xx_NEWLINE_xXMean corrected QT (QTc) > 450 ms at time of screeningXx_NEWLINE_xXPatients with a corrected QT using Fridericia's formula (QTcF) or corrected QT using Bazett's formula (QTcB) > 480 ms in the baseline electrocardiogram (EKG)Xx_NEWLINE_xXBazett-corrected QT (QTcB) interval ?501 msec at the time of transition to this studyXx_NEWLINE_xXBaseline corrected QT (QTc) > 480 msec or other clinically significant baseline electrocardiogram (ECG) abnormalityXx_NEWLINE_xXAt eltrombopag dose levels 200 mg and above cohorts, subjects with a corrected QT (QTc) > 480 msec at screening, if other drugs known to cause prolonged QT are stopped an electrocardiogram (EKG) documenting QTc below 480 msec is requiredXx_NEWLINE_xXQT related exclusion criteria:\r\n* QT interval corrected using Fridericia’s formula (QTcF) at screening > 470 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 intervalXx_NEWLINE_xXScreening electrocardiogram (ECG) with a corrected QT interval using Fridericia's formula (QTcFredericia)(QTcF) > 450 msecXx_NEWLINE_xXCorrected QT (QTc) interval >/= 480 msec at the time of transition to this studyXx_NEWLINE_xXNormal QT Fridericia-corrected interval (QTcF) ?450 ms for males and ?470 ms for femalesXx_NEWLINE_xXProlongation of corrected QT interval (QTc) > 480 msecsXx_NEWLINE_xXEXPANSION COHORT ONLY: Prolongation of corrected QT interval (QTc) > 480 msecsXx_NEWLINE_xXQTc > 450 msecXx_NEWLINE_xXHistory of significant cardiovascular disease, defined as:\r\n* Congestive heart failure greater than New York Heart Association (NYHA) class III according to the NYHA functional classification \r\n* Unstable angina or myocardial infarction within 6 months of enrollment\r\n* Serious cardiac arrhythmia\r\n* A prolonged QT/corrected QT (QTc) interval (QTc > 500 ms) demonstrated on electrocardiogram (ECG) at screening or baseline; a history of risk factors for torsade de pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome) or the use of concomitant medications that prolonged the QT/QTc intervalXx_NEWLINE_xXQTcF >500 msec (males or females)Xx_NEWLINE_xXTreatment with medications known to cause corrected QT (QTc) interval prolongation within 7 days of study day 1 is not permitted unless approved by the sponsor; use of ondansetron is permitted for treatment of nausea and vomitingXx_NEWLINE_xXClinically significant active cardiovascular disease or history of myocardial infarction within 3 months prior to planned start of LOXO-195 or prolongation of the QT interval corrected (QTcF) > 480 msec within the past 6 monthsXx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's correctionXx_NEWLINE_xXQT-interval corrected according to Fridericia's formula (QTcF) ? 450 ms on electrocardiogram (ECG) at ScreeningXx_NEWLINE_xXBaseline corrected QT interval (QTc) =< 480 msXx_NEWLINE_xXCurrent use of drugs that are known to prolong the QT intervalXx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from a single electrocardiogram or average from 3 electrocardiograms (ECGs) using Fridericia's correctionXx_NEWLINE_xXQTc > 470 msec on electrocardiogramXx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs)Xx_NEWLINE_xXSignificant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) >= 470 msecXx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Frederica’s correctionXx_NEWLINE_xXProlongation of corrected QT (QTc) interval to >480 milliseconds (ms)Xx_NEWLINE_xXPatients with any of the following:\r\n* History of myocardial infarction within six months\r\n* Patients with corrected QT (QTc) prolongation > 500 msec or other significant electrocardiogram (ECG) abnormality noted within 14 days of treatment\r\n** For patients enrolled in the Phase 1-T portion of the protocol, the QTc should not exceed 470 msec\r\n* New York Heart Association (NYHA) classification of III or IV\r\n* If cardiac function assessment is clinically indicated or performed: left ventricular ejection fraction (LVEF) less than normal per institutional guidelines, or < 55%, if threshold for normal not otherwise specified by institutional guidelines\r\n* Condition requiring concurrent use of drugs or biologics with pro-arrhythmic potentialXx_NEWLINE_xXMean QTc >= 450 msec (for males) or QTc >= 470 msec (for females)Xx_NEWLINE_xXClinically significant abnormality on electrocardiogram (ECG). The corrected QT interval (QTc, Fridericia) must be < 470 milliseconds for men and < 490 milliseconds for women (Must be confirmed by at least 2 additional 12-lead ECGs at least 2 minutes apart such that average manually over-read QTcF based on 3 ECGs exceeds stated thresholds)Xx_NEWLINE_xXCorrected QT interval (QTc) must be < 500 msecXx_NEWLINE_xXMean QTc > 500 msec (with Bazett’s correction) in screening electrocardiogram or history of familial long QT syndromeXx_NEWLINE_xXProlonged QTc interval on pre-entry electrocardiogram (> 470 msec)Xx_NEWLINE_xXQTc interval >0.45 secondsXx_NEWLINE_xXECG: QTc interval ? 450 msXx_NEWLINE_xXPatients must not have any clinically significant cardiovascular disease including the following: myocardial infarction or ventricular tachyarrhythmia within 6 months, prolonged corrected QT interval (QTc) > 480 msec (Fridericia correction), ejection fraction less than institutional normal, major conduction abnormality (unless a cardiac pacemaker is present); patients with any cardiopulmonary symptoms of unknown cause (e.g. shortness of breath, chest pain, etc.) are to be evaluated by a baseline echocardiogram with or without stress test as needed in addition to electrocardiogram (EKG) to rule out QTc prolongation; the patient may be referred to a cardiologist at the discretion of the principal investigator; patients with underlying cardiopulmonary dysfunction are excluded from the studyXx_NEWLINE_xXPatients must not have QTc prolongation defined as a QTc interval equal to or greater than 450 milliseconds (msecs)Xx_NEWLINE_xXMean QTcF ?450 msec (for males) or ?470 msec (for females) at ScreeningXx_NEWLINE_xXHas electrocardiogram (ECG) abnormalities that make QT interval corrected (QTc) evaluation difficult.Xx_NEWLINE_xXthe potential to prolong the QT interval, orXx_NEWLINE_xXClinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTCF) > 450 msXx_NEWLINE_xXInability to measure QT interval on ECGXx_NEWLINE_xXCorrected QT interval (QTc) < 470 ms (as calculated by the Fridericia correction formula).Xx_NEWLINE_xXBaseline prolongation of QT/corrected QT (QTc) interval, i.e., defined as an average QTc interval > 450 msec calculated using the Fridericia formula for QT correction; long QT syndrome; or the required use of concomitant medication that may cause torsade de pointesXx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia’s correctionXx_NEWLINE_xXPatients with QTcF >470 msec at screening ECG or congenital long QT syndromeXx_NEWLINE_xXHas a corrected QT interval (QTc) > 470 ms or has an electrocardiogram (ECG) with a new abnormal finding that is clinically significantXx_NEWLINE_xXGrade >= 2 QT interval corrected (QTc) prolongation on screening electrocardiogram (ECG) within 28 days of enrollment, or history of ventricular arrhythmiaXx_NEWLINE_xXBaseline mean QTcF ? 450 msec (for males) or ? 470 msec (for females) at Screening.Xx_NEWLINE_xXCorrected QT interval (QTc) < 470 msXx_NEWLINE_xXAppropriately corrected screening ECG QTc interval 470 msec for females, 450 msec for males.Xx_NEWLINE_xXCurrently receiving medications known to cause QT prolongation AND corrected QTc of 450 msec for females, 430 msec for males.Xx_NEWLINE_xXQT/QTc interval >480 msec, before C1D1 treatment administration, as determined by screening electrocardiogram (ECG)Xx_NEWLINE_xXSubject has QTcF interval > 450 ms on 12-lead ECG at screening.Xx_NEWLINE_xXSubject is taking medication known to prolong the QT interval.Xx_NEWLINE_xXImpaired cardiac function including ongoing cardiac dysrhythmias of grade > 2, ejection fraction < 50%, atrial fibrillation of any grade, or corrected QT (QTc) prolongation > 450 ms, or other factors that increase the risk of QT prolongation (i.e. family history of long QT interval syndrome, hypokalemia defined as serum potassium < 3.0 mEq/L)Xx_NEWLINE_xXQT/QTc interval > 450 msec, as determined by screening ECG performed no earlier than 1 week before C1D1Xx_NEWLINE_xXCorrected QT interval (QTc) greater than 450 msXx_NEWLINE_xXCorrected QT (QTc) interval >= 450 ms (ie, grade 1 or higher) on electrocardiogram (ECG) prior to initiation of study treatment\r\n* If baseline QTc on screening ECG is >= 450 ms (ie, grade 1 or higher):\r\n** Check potassium and magnesium serum levels\r\n** Correct any identified hypokalemia and/or hypomagnesemia and repeat ECG to confirm QTc interval\r\n* For patients with baseline heart rate (HR) < 60 beats per minute (bpm) or > 100 bpm, manual measurement of QT interval by cardiologist is required, with Fridericia correction applied to that manual measurement to determine the QTc for eligibility consideration\r\n* Note: For patients with HR 60-100 bpm, manual measurement of QTc interval and use of Fridericia calculation is NOT requiredXx_NEWLINE_xXClinically relevant findings in the ECG such as a second-degree or third-degree atrioventricular (AV) block (subjects with AV block and pacemaker in place for >1 year and checked by a cardiologist within ?6 months before the first dose of study drug will not be excluded), prolongation of the QRS complex over 120 msec or of the QTc interval (Fridericia, QTcF) over 470 msec (subjects with a pacemaker and QRS interval over 120 msec or QTc inverval over 470 msec may be enrolled on a case-by-case basis, following a discussion between the investigator and the sponsor).Xx_NEWLINE_xXHistory of long QT syndrome or whose corrected QT interval (QTc) measured (Fridericia method) at screening is prolonged (> 480 ms for males and females).Xx_NEWLINE_xXCorrected QT (QTc) interval =< 480 msXx_NEWLINE_xXImpaired 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 (< 45 beats per minute), d. QTc > 480 msec on baseline ECG; if QTc > 450 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) < 6 months prior to screening, symptomatic chronic heart failure, history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality < 6 months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardiaXx_NEWLINE_xXA QT interval corrected for heart rate using Bazett's formula QTcB >= 480 msecXx_NEWLINE_xXConcurrent administration of crizotinib and agents that can cause corrected QT (QTc) prolongation is not permittedXx_NEWLINE_xXParticipants with electrocardiogram (ECG) abnormalities considered by the investigator to be clinically significant, or repeated baseline prolongation of the rate-corrected QT interval (QTc).Xx_NEWLINE_xXParticipants with electrocardiogram (ECG) abnormalities considered by the investigator to be clinically significant, or repeated baseline prolongation of the rate-corrected QT interval (QTc).Xx_NEWLINE_xXCardiac function: 12-lead electrocardiogram (ECG) with normal tracing, or non-clinically significant changes that do not require medical intervention; corrected QT (QTc) interval is to be < 470 msecXx_NEWLINE_xXCorrected QT interval (QTc) > 470 msec on electrocardiogram (by Bazett’s; average of triplicate recordings at the discretion of the principal investigator [PI]) will exclude patients from entry on study; medications that are known to cause QTc interval prolongation are prohibited for patients entering on trial; patients for whom a given medication that may cause QTc interval prolongation cannot be discontinued, may be eligible at the discretion of the study PI, provided QTc interval criteria is met at enrollmentXx_NEWLINE_xXQTcF >480 msec on screening ECG or congenital long QT syndromeXx_NEWLINE_xXSubjects with a corrected QT interval (QTc) <450 milliseconds (msec) or <480msec for subjects with bundle branch block. The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF), machine or manual overread. For subject eligibility and withdrawal, QTcF will be used. For purposes of data analysis, QTcF will be used. The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording periodXx_NEWLINE_xXHas marked prolongation of QTc interval at screening or baseline using the Fridericia method of correction for heart rateXx_NEWLINE_xXParticipants with mean corrected QTc interval > 500 msec, as assessed within 4 weeks prior to enrollment, or participants who require medication known to prolong the QT intervalXx_NEWLINE_xXCorrected QT interval (QTc) >470 msec (as calculated by Fridericia correction formula) at study entry or congenital long QT syndrome.Xx_NEWLINE_xXCorrected QT interval (QTc) > 480 msecs using Bazett’s formulaXx_NEWLINE_xXCorrected QT (QTc) interval =< 480 msXx_NEWLINE_xXPre-treatment corrected QT (QTc) interval of greater than 490 msXx_NEWLINE_xX11. Corrected QT interval (QTc) < 470 ms (as calculated by the Fridericia correction formula).Xx_NEWLINE_xXCorrected QT interval (QTc) < 470 msXx_NEWLINE_xXNormal QT interval corrected (Fridericia) (QTcF) on screening electrocardiogram (ECG) evaluation, defined as QTcF of =< 450 ms in males or =< 470 ms in femalesXx_NEWLINE_xXCorrected QT interval (QTc) prolongation (defined as a QTc interval > 480 msec) or other significant electrocardiogram (ECG) abnormalitiesXx_NEWLINE_xXCorrected QT interval (QTc) > 480 msecs using Bazett's formula.Xx_NEWLINE_xXThe subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before day 1 of cycle 1; note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regardXx_NEWLINE_xXPredose mean QTc? 450 msec or QTcF ? 450 msec.Xx_NEWLINE_xXMean QTcF interval > 450 msec at screening.Xx_NEWLINE_xXHistory of congenital long QT syndrome or mean corrected QTc interval > 450 msec at baselineXx_NEWLINE_xXPatients with corrected QT (QTc) prolongation (defined as a QTc interval equal to or greater than 500 msec) or other significant electrocardiogram (ECG) abnormalities are excludedXx_NEWLINE_xXSubjects have a mean QT interval corrected by the Fridericia Correction formula value of >470 msec (in females) or >450 msec (in males)Xx_NEWLINE_xXNON-PROGRESSED DIPG (STRATUM 2): Patient has a QTc interval < 450 msXx_NEWLINE_xXCorrected QT (QTc) (Frederica) prolongation > 470 msecXx_NEWLINE_xXCorrected QT (QTc) interval =< 470 msecXx_NEWLINE_xXHas a QTc prolongation to > 450 millisecond (ms) in males and > 470 ms in females.Xx_NEWLINE_xXPatients with a corrected QT interval using Fridericia's formula (QTcF) interval of > 450 msec on screening electrocardiogram (ECG); Note: if > 450 msec on the first ECG, 2 additional ECGs can be ordered same day and then the average may be used to determine eligibilityXx_NEWLINE_xXMean resting corrected QT interval (QTc using Fridericia’s formula [QTcF]) > 470 msecXx_NEWLINE_xXClinically significant electrocardiogram (ECG) abnormality, including a marked Baseline prolonged QT interval/corrected QT interval ([QT/QTc], example, a repeated demonstration of a QTc interval >500 millisecond [ms]).Xx_NEWLINE_xXConsistent corrected QT (QTc) > 450 msec for men and > 470 msec for women by Fridericia formula, on 3 separate electrocardiograms (ECGs); patients with a history of long QTc syndrome or personal or family history of ventricular arrhythmias will be excludedXx_NEWLINE_xXBaseline prolongation of the rate-corrected QT interval (QTc) > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointesXx_NEWLINE_xXQTcF > 470 msec on Screening ECG (mean of triplicate recordings).Xx_NEWLINE_xXScreening electrocardiogram (EKG) with a corrected QT (QTc) > 450 msecXx_NEWLINE_xXPatients with significant cardiovascular disease (New York Heart Association class III or IV cardiac disease), symptomatic congestive heart failure, myocardial infarction within the past 6 months, unstable angina, unstable arrhythmia or a need for anti-arrhythmic therapy (use of frequency adjusting medication for atrial fibrillation is allowed, if stable medication for at least last month prior to initiation of belinostat treatment and medication not listed as causing Torsades de Pointes), or evidence of acute ischemia on electrocardiogram (ECG); marked baseline prolongation of QT/corrected QT (QTc) interval, e.g., repeated demonstration of a QTc interval > 450 msec; long QT syndrome; concomitant use of drugs known to prolong the QT interval and/or cause Torsades de Pointes is not allowed during the study or within 2 weeks of study entry; these drugs should also be avoided for up to 4 weeks following discontinuation of study treatment; drugs that may be associated with Torsades de Pointes but lack substantial evidence will be allowed at the discretion of the PI (although it is preferable to substitute an alternate medication), and patients will be closely monitoredXx_NEWLINE_xXQTcF > 470 msec on the screening ECGXx_NEWLINE_xXHave corrected QT (QTc) interval of >470 milliseconds on screening electrocardiogram (ECG).Xx_NEWLINE_xXThe subject has a corrected QT interval (QTc) > 480 ms at screening or has a history of long QT syndromeXx_NEWLINE_xXHave Fridericia-corrected QT interval (QTcF) >480 milliseconds on screening electrocardiogram (ECG).Xx_NEWLINE_xXHistory of congenital long QT syndrome or QTc > 470 msecXx_NEWLINE_xXHave Fridericia-corrected QT interval > 470 milliseconds (msec) (female) or > 450 msec (male), or history of congenital long QT syndromeXx_NEWLINE_xXCongenital long QT syndrome or QT interval corrected using Fridericia's formula (QTcF) >470 milliseconds (msec)Xx_NEWLINE_xXConcurrent medications associated with a risk of corrected QT (QTc) prolongation and/or torsades de pointes are not allowed; those medications listed as reported but lacking substantial evidence for causing QTc prolongation and torsades de pointes will be allowed, although if an alternative medication can be substituted, that would be preferable; for this study, a baseline electrocardiogram (EKG) will be performed and will be repeated during cycle 1 and then every 3 cycles while on treatmentXx_NEWLINE_xXPatients with current evidence of significant cardiovascular disease (New York Heart Association class III or IV cardiac disease), symptomatic congestive heart failure, dilated/hypertrophic or restrictive cardiomyopathy, myocardial infarction (within the past 6 months), unstable angina, unstable arrhythmia or a need for anti-arrhythmic therapy (use of medications for rate control for atrial fibrillation is allowed such as calcium channel blockers and beta-blockers, if stable medication for at least last month prior to initiation of MK-2206 treatment and medication not listed as causing torsades de pointes), or evidence of acute ischemia on electrocardiogram (ECG); marked baseline prolongation of QT/QTc interval, e.g., repeated demonstration of a QTc interval > 450 msec*; long QT syndrome; the required use of concomitant medication that may cause torsades de pointes or may cause a significant prolongation of the QTc\r\n*Note: Due to difficulties assessing QTc in patients with heart block, they may be eligible if deemed safe by a cardiologistXx_NEWLINE_xXCardiac ejection fraction ?50%, and QTcF<450 ms (males) or <470 ms (females) on ECG at Baseline.Xx_NEWLINE_xXScreening ECG with a QTc > 450 msec.Xx_NEWLINE_xXUncontrolled or severe cardiovascular disease, including myocardial infarction, unstable angina, or atrial fibrillation (AFib) within 6 months prior to study treatment, New York Heart Association (NYHA) class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease, cardiac amyloidosis, or corrected QT (QTc) with Fridericia’s (QTcF) correction that is unmeasurable or >= 480 msec on screening electrocardiography (ECG); (Note: for QTcF >= 480 sec on the screening ECG, the ECG may be repeated twice at least 24 hours apart; the mean QTcF from the three screening ECGs must be < 480 msec in order to meet eligibility for trial participation)Xx_NEWLINE_xXCorrected QT interval (QTc) using Fridericia's formula value > 480 msec at screening; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy at screening; previous history of drug induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on electrocardiogram (ECG).Xx_NEWLINE_xXClinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTcF) >450 msXx_NEWLINE_xXInability to measure QT interval on ECGXx_NEWLINE_xXA baseline QT interval as corrected by Fridericia's formula (QTcF) > 450 msec, a complete left bundle branch block (defined as a QRS interval ? 120 msec in left bundle branch block form) or an incomplete left bundle branch block.Xx_NEWLINE_xXCorrected QT (QTc) interval ? 450 msec at baseline or history of congenital long QT syndrome or uncorrectable electrolyte abnormalities. (Patients with well controlled atrial fibrillation are exempt from this criteria.)Xx_NEWLINE_xXHistory of long QT syndrome or whose corrected QT interval (QTc) measured (Fridericia method) at screening is prolonged (> 450 ms for males and > 470 ms for females). Individuals who screen-fail due to this criterion are not eligible to be re-screenedXx_NEWLINE_xXSubject with a QTcF of > 450 msec in male subjects and > 470 msec in female subjects on the screening 12 lead ECG.Xx_NEWLINE_xXPatients with baseline QTcF ? 480 msecXx_NEWLINE_xXPatients with Common Terminology Criteria for Adverse Events (CTCAE) grade 2 cardiac arrhythmias may be considered for inclusion if the arrhythmias are stable, asymptomatic, and unlikely to affect patient safety; patients will be excluded if they have ongoing cardiac dysrhythmias of CTCAE grade >= 3, corrected QT interval (QTc) prolongation > 450 ms, or other factors that increase the risk for QT interval prolongation (eg, heart failure, hypokalemia [defined as serum potassium < 3.0 mEq/L that is persistent and refractory to correction], or family history of long QT interval syndrome)Xx_NEWLINE_xXHeart-rate corrected QT (QTc) interval >450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome). Subjects with right bundle branch block and a prolonged QTc interval should be reviewed by the Medical Monitor for potential inclusionXx_NEWLINE_xXSubjects taking medications that are known to prolong the QT intervalXx_NEWLINE_xXCorrected QT interval using Fridericia's formula (QTcF) interval equal to or less than 470 msecXx_NEWLINE_xXQTcF ? 450 msec for males or 470 msec for females.Xx_NEWLINE_xXScreening and Baseline QTcF (Fridericia's) less than 470 msecXx_NEWLINE_xXPatients taking medications known to prolong the QTc interval directly or that interact pharmacodynamically with medicines to prolong the QTc interval.Xx_NEWLINE_xXMust not have QT interval of >470 millisecond.Xx_NEWLINE_xXCorrected QT interval (QTc) > 500 milliseconds in a 12-lead electrocardiogram (ECG) during screening.Xx_NEWLINE_xXPatient has clinically significant resting bradycardia (heart rate < 50 at rest), tachycardia (heart rate > 90 at rest), PR interval > 220 msec, QRS interval > 109 msec, or QTcF > 450 msec.Xx_NEWLINE_xXCorrected QT interval (QTc) of > 450 milliseconds (ms) in males and > 470 milliseconds (ms) in females on baseline electrocardiogram (ECG) (using Fridericia [QTcF] corrected QT intervalXx_NEWLINE_xXClinically active heart disease including prolonged QTc or prolonged PR interval, or history of arrhythmiasXx_NEWLINE_xXPatients must have corrected QT (QTC) interval =< 480 msec on electrocardiogram (EKG) at baseline; patient with congenital long QT syndrome are not eligibleXx_NEWLINE_xXCorrected QT interval (QTc) > 480 msecXx_NEWLINE_xXProlonged rate corrected QT interval (QTc) >=500 millisecond (msec), calculated according to institutional guidelines.Xx_NEWLINE_xXPatients with a baseline QT/corrected QT (QTc) interval >= 501 msecXx_NEWLINE_xXPatients who have, at screening, corrected QT interval using Fridericia's formula (QTcF) >= 450 msec for males and QTcF >= 470 for femalesXx_NEWLINE_xXA QT interval corrected for heart rate using the Bazett's formula (QTcB) >=480 millisecond (msec);Xx_NEWLINE_xXProlongation of corrected QT interval by Fridericia's method (QTcF) at rest, where the mean QTcF interval is > 450 ms for males and > 470 ms for females based on triplicate electrocardiogram (ECG).Xx_NEWLINE_xXBaseline corrected QT interval (QTc) > 470 msec (average of triplicate electrocardiogram [ECG] recordings); a consistent method of QTc calculation must be used for each patient's QTc measurements; QTcF (Fridericia's formula) is preferredXx_NEWLINE_xXBaseline QTc >470 msec and/or previous history of QT prolongation while taking other medications.Xx_NEWLINE_xXCorrected QT (QTc) interval =< 480 msXx_NEWLINE_xXPatients should not be allergic to eggs or soy beans. Patients must be medically, psychologically and neurologically stable and have triplicate baseline ECG's with a mean QTc interval <500 ms and >300 ms and neither a history of congenital prolonged or short QT syndrome. Patients with a history of cardiac disease must be stable.Xx_NEWLINE_xXQTcF interval on electrocardiogram (ECG) at screening > 450 msec for males or > 460 for females;Xx_NEWLINE_xXBaseline ATc>470 msec and/or previous history of QT prolongation.Xx_NEWLINE_xXCorrected QT (QTc) interval using Bazett's Formula; (QTcB) >= 480 msecsXx_NEWLINE_xXImportant abnormalities of the ECG that may interfere with the interpretation of QTc interval changes at screeningXx_NEWLINE_xXQTc (corrected QT) interval < 480 msec.Xx_NEWLINE_xXPatients must have an electrocardiogram (EKG) documenting normal intervals (especially QTc interval < 480 msec) and no arrhythmia prior to enrollmentXx_NEWLINE_xXMean QTc interval >= 480 msec at screeningXx_NEWLINE_xXMean corrected QT (QTc) interval >= 450 (triplicate electrocardiograms [ECGs]) or history congenital prolonged QT intervalXx_NEWLINE_xXCorrected QT (QTc) interval >= 500 millisecondsXx_NEWLINE_xXBaseline QTc exceeding 450 msec (470 msec for females) using the Bazetts formula and/or patients receiving class 1A or class III antiarrythmic agents.Xx_NEWLINE_xXThe patient has QTcF interval greater than 450 msec, has a known history of QTcF prolongation, is taking medications known to prolong QTcF, or has a history of torsade de pointes.Xx_NEWLINE_xXClinically relevant findings in the ECG such as a second- or third-degree AV block, prolongation of the QRS complex over 120 msec or of the QTcF-interval over 450 msecXx_NEWLINE_xXCorrected QT (QTc) interval > 450 msec (males) or > 470 msec (females)Xx_NEWLINE_xXQTc interval <= 300 msecXx_NEWLINE_xXQT interval measurement corrected by Fridericia's formula (QTcF) interval of >450 msec (males) or >470 msec (females)Xx_NEWLINE_xXScreening ECG QTc interval ? 470 msec for females, ? 450 msec for males.Xx_NEWLINE_xXAt increased risk for developing prolonged QT interval, including hypokalemia or hypomagnesemia, unless corrected to within normal limits prior to first dose of SNX-5422; congenital long QT syndrome or a history of torsade de pointes; currently receiving anti-arrhythmics or other medications that may be associated with QT prolongationXx_NEWLINE_xXSubjects with a QT interval corrected for heart rate according to Bazett's formula (QTcB) <450millisecond (msec) or <480msec for subjects with bundle branch block. The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period.Xx_NEWLINE_xXElectrocardiogram (12-lead ECG) QTc ? 480 msXx_NEWLINE_xXCorrected QT interval (QTc) of greater than 500 msecXx_NEWLINE_xXPatients with a corrected QT interval (QTc) at baseline of > 450 milliseconds or other factors that increase the risk of QT prolongation or arrhythmic events (i.e., heart failure, hypokalemia with potassium < 3.5 despite supplementation, family history of long QT syndrome) should be excludedXx_NEWLINE_xXElectrocardiogram (EKG) abnormalities of:\r\n* Q-wave infarction, unless identified 6 or more months prior to screening\r\n* QTc interval > 470 msec, the upper limit of normal for womenXx_NEWLINE_xXPatients must not have prolonged corrected QT (QTc) interval (> 500 msec) determined by electrocardiogram (EKG) within 28 days prior to registrationXx_NEWLINE_xXCardiovascular baseline corrected QT by Fridericia's (QTcF) > 450 msec (male) or QTcF > 470 msec (female) will exclude patients from entry on studyXx_NEWLINE_xXQTcF corrected with Frederica's or Bazett's formula QTcB >450 ms for males and >470 ms for females on screening ECG.Xx_NEWLINE_xXA corrected QT interval >=480 msec (e.g. Bazett's formula [QTcB])Xx_NEWLINE_xXQT/QTc interval >450 msec, as determined by screening electrocardiogram (ECG)Xx_NEWLINE_xXQTcF interval > 450 msec (males) or > 470 msec (females)Xx_NEWLINE_xXSerious cardiac condition such as myocardial infarction within the past 6 months, unstable angina, or Class III or IV congestive heart failure as defined by the New York Heart Association (NYHA); have ECG abnormalities including baseline 12-lead ECG with Fridericia-corrected QT interval (QTcF) > 470 msec (female) or > 450 msec (male), a history of congenital long QT syndrome, or any ECG abnormality that, in the opinion of the Investigator, would preclude safe participation in the studyXx_NEWLINE_xXQTc interval prolongation >450ms for males and >470 ms for females.Xx_NEWLINE_xXKnown history of QT prolongation or is taking any medication known to lead to QT prolongationXx_NEWLINE_xXConcomitant medication that may cause Torsade de Pointes, i.e. prolongation of the QT interval > 500 msecXx_NEWLINE_xXCurrent long QT syndrome or baseline prolongation of QT/QTcF interval, i.e. demonstration of a QTcF interval > 450 msecXx_NEWLINE_xXPatients with a mean QTc interval greater than 480ms are excluded. Avoid concomitant administration of agents that prolong the QT interval, except at the discretion of the investigator. If advised, patients should discontinue the use of these agents at least 2 weeks before the study begins. No uncontrolled arrhythmias.Xx_NEWLINE_xXProlonged corrected QT interval by the Fridericia correction formula (QTcF) on the Electrocardiogram (ECG) > 470 msec.Xx_NEWLINE_xXPatients may not have any clinically significant cardiovascular disease including the following:\r\n* Myocardial infarction or ventricular tachyarrhythmia within 6 months\r\n* Prolonged corrected QT interval (QTc) > 480 msec\r\n* Ejection fraction less than 50%\r\n* Major conduction abnormality (unless a cardiac pacemaker is present)Xx_NEWLINE_xXHave chronic atrial fibrillation or QTc interval corrected for heart rate of greater than 470 msec.Xx_NEWLINE_xXAt increased risk for developing prolonged QT interval, including hypokalemia or hypomagnesemia, unless corrected to within normal limits prior to first dose of SNX-• Chronic diarrhea.Xx_NEWLINE_xXPatient must have a QT/QTc interval ? 450 msec.Xx_NEWLINE_xXPatient with prolonged QT/QTc (defined as QTc interval > 450 msec) are not eligible.Xx_NEWLINE_xXMust have a QT interval corrected for heart rate according to Fridericia's formula (QTcF) <470 milli seconds (msec) or <480 msec with bundle branch block.Xx_NEWLINE_xXThe subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before enrollment; note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regardXx_NEWLINE_xXThe subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 14 days before week 1 day 1Xx_NEWLINE_xXCorrected QT interval (QTc) < 480 msec (with Bazett’s correction) in screening electrocardiogramXx_NEWLINE_xXHistory of familial long QT syndrome, or use of medications that may cause QTc interval prolongationXx_NEWLINE_xXNormal ejection fraction (echocardiogram [ECHO] or cardiac MRI) >= 53% (or the institutional normal; if a range is given then the upper value of the range will be used); corrected QT (QTC) or Fridericia's correction formula (QTcF) =< 450 msecXx_NEWLINE_xXPatient has a QT interval prolongation > 480 ms at screening. If a patient has a prolonged QT interval and the prolongation is deemed to be due to a pacemaker upon Investigator evaluation (ie, the patient otherwise has no cardiac abnormalities), then the patient may be eligible to participate in the study following discussion with the Medical Monitor.Xx_NEWLINE_xXCorrected QT (QTc) interval > 500 msec (Bazett formula or Fridericia formula based on institutional standard)Xx_NEWLINE_xXPretreatment QTcF interval >470 msec (females) or >450 msec (males)Xx_NEWLINE_xXElectrocardiogram (EKG) with mean corrected QT (QTc) interval < 450 msecXx_NEWLINE_xXA baseline ECG QTcF > 470 msecXx_NEWLINE_xXCorrected QT (QTc) interval > 500 msec on baseline electrocardiogram (EKG)Xx_NEWLINE_xXDocumented history of prolonged QTc interval =< 6 months prior to registrationXx_NEWLINE_xXProlonged QTc interval on pre-entry electrocardiogram (> 450 msec) on the Bazett’s correctionXx_NEWLINE_xXBaseline QTc > 470 msec or previous history of QT prolongation while taking other medicationsXx_NEWLINE_xXGrade > 1 QTc prolongation at baseline (> 450 msec by Bazett formula) confirmed by a repeat electrocardiogram (ECG)Xx_NEWLINE_xXAt Screening, QTcF >450 msec for males; QTcF >470 msec for femalesXx_NEWLINE_xXCorrected QT interval > 480 msecs using Bazett's formula.Xx_NEWLINE_xXSubjects with a high probability of Long QT Syndrome or QTc interval prolongation of more than or equal to 501 msec on at least two separate ECGs, following correction of any electrolyte imbalance.Xx_NEWLINE_xXPatient has a QTcF value of >480 msec; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy; previous history of drug-induced QTc prolongationXx_NEWLINE_xXCorrected QT (QTc) interval > 500 msecXx_NEWLINE_xXQTc greater than 470 msec.Xx_NEWLINE_xXHave a QTc interval greater than 470 msecXx_NEWLINE_xXA baseline ECG QTc > 470 msXx_NEWLINE_xXBaseline corrected QT interval (QTc) > 450 msXx_NEWLINE_xXCorrected QT (QTc) prolongation with other medications; if the medication can be discontinued and an alternative medication started that does not cause QTc prolongation, the patient would be eligible; if no alternative medication is available and the medication cannot be discontinued for medical reasons, then the patient would not be eligibleXx_NEWLINE_xXQTc with Fridericia’s correction that is not measurable, or >= 480 msec on screening electrocardiogram (ECG); (Note: if a patient has a QTc interval >= 480 msec on screening ECG, the screen ECG may be repeated twice [at least 24 hours apart]; the average QTc from the three screening ECGs must be < 480 msec in order for the patient to be eligible for the study); patients who are receiving a drug that has a risk of QTc prolongation are excluded if QTc is >= 460 msecXx_NEWLINE_xXQTcF >450 ms for males and >470 ms for females on screening ECGXx_NEWLINE_xXHave QTc interval of >500 msec on screening electrocardiogramXx_NEWLINE_xXProlonged QTC interval >450msXx_NEWLINE_xXProlonged QTc interval (males >450ms, females >470ms)Xx_NEWLINE_xXProlonged QTc interval (males >450ms, females >470ms)Xx_NEWLINE_xXCorrected (Bazett) QTc interval of > .50 ms (male) or > .52 ms (female)Xx_NEWLINE_xXProlongation of corrected QT interval (QTc) > 480 milliseconds (msec)Xx_NEWLINE_xXCorrected QT interval (QTc) ? 450 msec at least 7 days prior to registration for protocol therapy.Xx_NEWLINE_xXPatients must not have a marked baseline prolongation of QT/corrected QT (QTc) interval (e.g., demonstration of a QTc interval > 500 milliseconds (ms)Xx_NEWLINE_xXQTc prolongation defined as a QTc greater than or equal to 470 ms or a prior history of cardiovascular disease, arrhythmias, or significant ECG abnormalitiesXx_NEWLINE_xXMust have electrocardiogram (EKG) with corrected QT (QTc) interval < 450 msec and Echocardiogram with shortening fraction >= 27% or ejection fraction > 50%Xx_NEWLINE_xXShortening fraction greater than or equal to 27% by echocardiogram; corrected QT interval =< 450 millisecondsXx_NEWLINE_xXPatients using medications that have a relative risk of prolonging the QT intervalXx_NEWLINE_xXQTcF interval < 450 msec and mean resting heart rate 50-90 bpmXx_NEWLINE_xXQT interval corrected for heart rate using Fridericia’s formula (QTcF) >= 70 ms; any clinically significant abnormalities detected, require triplicate electrocardiography (ECG) results and a mean QT interval corrected for heart rate using Fridericia’s formula (QTcF) >= 470 ms calculated from 3 ECGsXx_NEWLINE_xXCorrect QT (QTc) longer than 500 msXx_NEWLINE_xXPatients with marked baseline prolongation of QT/corrected QT (QTc) interval (QTc interval > 450 msec for males or > 470 msec for females) using the Fridericia method for QTc analysisXx_NEWLINE_xXFridericia's corrected QT (QTcF) prolongation > 470 ms or QT prolongation deemed clinically relevant by the investigator (e.g., congenital long QT syndrome); the QTcF will be calculated as the mean of the 3 electrocardiograms (ECGs) taken at screening\r\n* NOTE: The formula used to calculate QTcF can be physician’s choice, but it must be used consistently throughout the studyXx_NEWLINE_xXAny of the following cardiac abnormalities or history:\r\n* Clinically significant abnormal 12-lead electrocardiograph (ECG), QT interval corrected using Fridericia's method (QTcF) > 450 msec\r\n* Inability to measure QT interval on ECG\r\n* Personal or family history of long QT syndrome\r\n* Implantable pacemaker or implantable cardioverter defibrillator\r\n* Resting bradycardia < 55 beats/minXx_NEWLINE_xXCorrected QT interval (QTc) > 470 milliseconds on baseline electrocardiogram (ECG) (using corrected QT interval using Fridericia [QTcF] or Bazett [QTcB]); if electrolytes are abnormal, they may be corrected and baseline ECG should be repeatedXx_NEWLINE_xXCorrected QT (QTc) =< 450 msXx_NEWLINE_xXCardiovascular disease, including recent history of or currently clinically symptomatic and uncontrolled congestive heart failure, arrhythmia, angina, corrected QT (QTc) prolongation or other QTc risk factors, myocardial infarction; patients with Common Terminology Criteria for Adverse Events (CTCAE) grade 2 cardiac arrhythmias may be considered for inclusion if the arrhythmias are stable, asymptomatic, and unlikely to affect patient safety; patients will be excluded if they have ongoing cardiac dysrhythmias of CTCAE grade >= 3, corrected QT interval (QTc) prolongation > 450 ms, or other factors that increase the risk for QT interval prolongation (e.g., heart failure, hypokalemia [defined as serum potassium < 3.0 mEq/L that is persistent and refractory to correction], or family history of long QT interval syndrome)Xx_NEWLINE_xXAny concomitant medications that are associated with a risk of corrected QT (QTc) prolongation and/or Torsades de Pointes should be discontinued or replaced with drugs that do not carry these risks, if possible; patients who must take medication with a possible risk of Torsades de Pointes should be watched carefully for symptoms of QTc prolongation, such as syncope; patients with personal or family history of congenital long QTc syndrome are NOT eligibleXx_NEWLINE_xXCorrected QT interval (QTc) > 480 msecsXx_NEWLINE_xXCorrected QT interval (QTc) > 480 msecs (record QTc correction method)Xx_NEWLINE_xXProlongation of corrected QT interval of > 480 msXx_NEWLINE_xXCorrected QT (QTc) interval =< 480 msXx_NEWLINE_xXProlonged corrected interval between the Q wave and T wave (QTc) by Fridericia's correction factor (QTcF) interval on pre-entry ECG ?450 ms (average of 3 ECG readings done in triplicate);Xx_NEWLINE_xXPatients may not currently be taking quinidine, ceritinib, highest risk corrected QT interval (QTc)-prolonging agents, mifepristone, or succinylcholineXx_NEWLINE_xXPatients must have electrocardiogram with corrected QT (QTc) with correction within 28 days prior to registrationXx_NEWLINE_xXRisk factors for torsades de pointes such as:\r\n* Uncontrolled hypokalemia\r\n* Uncontrolled hypomagnesemia or hypermagnesemia\r\n* Cardiac failure (New York Heart Association class II or higher)\r\n* Clinically significant/symptomatic bradycardia (hear rate [HR] < 50), or high-grade atrioventricular (AV) block\r\n* Known diagnosis of QT prolongation (QTc >= 470) or family history of long QT syndrome\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 medications known to prolong the QT interval during the same time as pasireotide is to be administered (unless approved by principal investigator [PI] and QTc < 470; standard transplant medications that are known to prolong the QT (e.g. azoles, ondansetron, etc.) are permitted but caution is advised and patients should be closely monitored)Xx_NEWLINE_xXBaseline QTc ?470 msec and no previous history of QT prolongation while taking other medications.Xx_NEWLINE_xXClinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolonged QT/QTc ([QT interval/corrected QT interval], e.g., a repeated demonstration of a QTc interval > 500 ms)Xx_NEWLINE_xXEXCLUSION CRITERIA FOR CROSSOVER THERAPY: Clinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolonged QT/QTc ([QT interval/corrected QT interval], e.g., a repeated demonstration of a QTc interval > 500 ms)Xx_NEWLINE_xXCurrent treatment with medications known to prolong the QT interval Stage I:Xx_NEWLINE_xXSubject has electrocardiogram (ECG) showing clinically significant abnormality at screening or an average QTc interval (Fridercia's or Bazett's formula) >450 msec in males and >470 msec in females (>480 msec for subjects with Bundle Branch Block (BBB)).Xx_NEWLINE_xXMean QT interval corrected for heart rate (QTc) < 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's correctionXx_NEWLINE_xXFriderichia corrected QT interval (QTcF) >450 milliseconds (msec) (men) or >475 msec (women) on a 12-lead electrocardiogram (ECG) during the Screening period.Xx_NEWLINE_xXProlongation of QTcF interval to >480 milliseconds (msec)Xx_NEWLINE_xXCorrected QT interval (QTc) =< 480 msecXx_NEWLINE_xXQT interval corrected for heart rate according to Fridericia's formula (QTcF) <450 milliseconds (msec) or QTcF <480 msec for subjects with bundle branch block.Xx_NEWLINE_xXMedical disorder that would endanger subject’s well-being (e.g., uncorrected hypothyroidism, cardiac arrhythmia, hypertension requiring treatment, sick sinus syndrome, prolonged corrected QT [QTc])Xx_NEWLINE_xXPATIENTS: History of prolonged corrected QT (QTc) interval (> 500 ms)Xx_NEWLINE_xXPatients with corrected QT (QTc) interval greater than 450 msXx_NEWLINE_xXCurrent evidence of cardiac arrhythmias defined as corrected QD interval (QTc) >= 480 mm/secXx_NEWLINE_xXQ-T interval of =< 450 ms as measured by electrocardiography (EKG)Xx_NEWLINE_xXPatients with a known or screening-period-determined corrected QT (QTc) interval > 450 msec and patients who require a therapy with a drug known to prolong the QT/QTc interval, are ineligibleXx_NEWLINE_xXPatients on medications that prolong QT interval, per principal investigator (PI) discretionXx_NEWLINE_xXPatients must not have baseline corrected QT (QTc) interval >= 500 msXx_NEWLINE_xXDiagnosis of narcolepsy, sick sinus syndrome, arrhythmia, or prolonged corrected QT interval (QTc)Xx_NEWLINE_xXPatients with a known pathologic prolongation of the corrected QT (QTc)Xx_NEWLINE_xXCorrected QT (QTc) interval within normal range for ageXx_NEWLINE_xXFridericia's Heart Rate Correction Formula (QTcF) interval >450 msec;Xx_NEWLINE_xXBaseline Fridericia corrected QT (QTcF) > 480 ms; NOTE: this criterion does not apply to patients with a left bundle branch blockXx_NEWLINE_xXQT interval corrected using Fridericia's formula (QTcF) >450 millisecondsXx_NEWLINE_xXFridericia's correction formula (QTcF) =< 470 msecXx_NEWLINE_xXQTc interval < 480 milliseconds (msec) on the baseline electrocardiogram.Xx_NEWLINE_xXPreviously documented and persistent corrected QT (QTc) prolongation (> 500 ms)Xx_NEWLINE_xXPatient must have an electrocardiogram without evidence of arrhythmia, QT prolongation (corrected QT [QTc] > 450 ms in males and > 470 ms in females), or other severe dysfunction within 2 weeks of registrationXx_NEWLINE_xXCorrected QT interval (QTc) =< 480 msecXx_NEWLINE_xXPatients with a QT interval corrected by Fridericia's formula (QTcF) > 450 msec (QTcF > 480 msec for patients with bundle branch block)Xx_NEWLINE_xXHas an 12-lead ECG obtained at screening visit which shows medically significant abnormality(ies) (e.g. left bundle branch block, frequent premature ventricular contractions, QTc interval prolongation > 450 msec for males and > 470 msec for females)Xx_NEWLINE_xXSubjects having an electrocardiogram with a prolonged corrected QT (QTc) interval by manual reading: QTc greater than 490 msecXx_NEWLINE_xXCorrected QT interval (QTc) > 450 msec (male) or > 470 msec (female) on 12-lead electrocardiogramXx_NEWLINE_xXScreening ECG with a QTc > 450 msec. If QTc > 450 and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient rescreened for QTc.Xx_NEWLINE_xXPatients with familial short QT syndrome or with corrected QT (QTc) interval =< 300 msXx_NEWLINE_xXMarked baseline prolongation of QT/corrected QT (QTc) interval (e.g. demonstration of a QTc interval greater than 500 milliseconds)Xx_NEWLINE_xXCorrected QT interval (QTc) > 450 ms per Fridericia’s correctionXx_NEWLINE_xXPrevious history of Corrected QT Interval (QTc ) prolongation resulting from medication that required discontinuation of that medicationXx_NEWLINE_xXQTc with Fridericia's correction that is unmeasurable, or ? 480 msec on screening ECG. The average QTc from the screening ECG (completed in triplicate) must be < 480 msec in order for the patient to be eligible for the study;Xx_NEWLINE_xXSubjects taking any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes are not eligible if QTc ? 460 msec.Xx_NEWLINE_xXHas QTc (QT interval corrected for rate) prolongation defined as: a) Symptomatic QTc prolongation >450 msec (males) or >470 msec (females) OR b) Any QTc prolongation of >500 msecXx_NEWLINE_xXProlonged QTc interval >450 msecXx_NEWLINE_xXQTCF > 450 ms, inability to measure QT interval on ECG, personal or family history of long QT syndrome, requirement for medications that have the potential to prolong the QT intervalXx_NEWLINE_xXPatients with corrected QT (QTc) interval > 0.47 secondsXx_NEWLINE_xXPatients with baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes) are ineligibleXx_NEWLINE_xXConcurrent medications associated with a known risk of corrected QT interval (QTc) prolongation and/or Torsades de Pointes are not allowed within 2 weeks of initiation of study treatment; those medications listed as a possible risk for causing QTc prolongation and Torsades de Pointes will be allowed, although if an alternative medication can be substituted, that would be preferable; granisetron is an acceptable antiemetic on this study, but if a patient must take ondansetron, they may NOT take any other concomitant agents which might impact their QTcXx_NEWLINE_xXPatients with current evidence of significant cardiovascular disease (New York Heart Association class III or IV cardiac disease), symptomatic congestive heart failure, dilated/hypertrophic or restrictive cardiomyopathy, myocardial infarction (within the past 6 months), unstable angina, unstable arrhythmia or a need for anti-arrhythmic therapy (use of medications for rate control for atrial fibrillation is allowed such as calcium channel blockers and beta-blockers, if stable medication for at least last month prior to initiation of romidepsin treatment and medication not listed as causing Torsades de Pointes), or evidence of acute ischemia on electrocardiogram (ECG); marked baseline prolongation of QT/QTc interval, e.g., repeated demonstration of a QTc interval > 450 msec*; long QT syndrome; the required use of concomitant medication that may cause Torsades de Pointes or may cause a significant prolongation of the QTc\r\n* Note: due to difficulties assessing QTc in patients with heart block, they may be eligible if deemed safe by a cardiologist; if a patient must take ondansetron as their antiemetic, their QTc may NOT be over 450 (no exception for patients with heart block)Xx_NEWLINE_xXAbnormal ECGs (ie, QT prolongation - QTc > 480 msec, signs of cardiac enlargement or hypertrophy, bundle branch block, signs of ischemia or necrosis and Wolff Parkinson White patterns)Xx_NEWLINE_xXMean QT interval corrected for heart rate (corrected QT [QTc]) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's correctionXx_NEWLINE_xXSubject has a QTcF > 480 ms (corrected) in the screening or baseline ECG.Xx_NEWLINE_xXProlongation of the corrected QT interval by Fridericia's formula (QTcF) interval defined as > 450 msec for males and > 470 msec for femalesXx_NEWLINE_xXCorrected QT (QTc) (Fredericia’s formula) < 470 msXx_NEWLINE_xXClinically 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 6 months prior to study entry\r\n* Documented cardiomyopathy\r\n* Left ventricular ejection fraction (LVEF) < 50% 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 torsade’s de pointes\r\n** Uncorrected hypomagnesemia or hypokalemia\r\n** Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg\r\n** Bradycardia (heart rate < 50 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 > 450 screening ECG (based on a mean of 3 ECGs)Xx_NEWLINE_xXCorrected QT (QTc) prolongation with other medications that required discontinuation of that medicationXx_NEWLINE_xXQTc with Bazett’s correction that is unmeasurable or >= 450 msec on screening electrocardiogram (ECG); (Note: if a subject has a QTc interval >= 450 msec on screening ECG, the screen ECG may be repeated twice [at least 24 hours apart]; the average QTc from the three screening ECGs must be < 450 msec in order for the subject to be eligible for the study)Xx_NEWLINE_xXHas a known history of QT prolongation or is taking any medication that is known to lead to QT prolongationXx_NEWLINE_xXEvidence of corrected QT (QTc) prolongation on pre-treatment electrocardiography (ECG) (greater than 440 ms in males or greater than 460 ms in females)Xx_NEWLINE_xXEvidence of corrected QT (QTc) prolongation on pretreatment electrocardiography (ECG) (greater than 440 ms in males or greater than 460 ms in females)Xx_NEWLINE_xXA history of clinically significant electrocardiography (EKG) abnormalities, including QT prolongation (Fridericia corrected QT interval [QTcF] > 500 ms), a family history of prolonged QT interval syndrome, or myocardial infarction (MI) within 6 months of study entry; patients with rate-controlled atrial fibrillation/flutter will be allowed on studyXx_NEWLINE_xXA history of clinically significant electrocardiography (EKG) abnormalities, including QT prolongation (QT interval by Fridericia's correction formula [QTcF] > 500 ms), a family history of prolonged QT interval syndrome, or myocardial infarction (MI) within 6 months of study entry; patients with rate-controlled atrial fibrillation/flutter will be allowed on studyXx_NEWLINE_xXPatient must not have corrected QT interval (QTc) > 480 msecs using Bazett’s formulaXx_NEWLINE_xXCardiovascular risk, including:\r\n* Poorly controlled hypertension, defined as either systolic > 170 or diastolic > 110\r\n* Congestive heart failure\r\n* Myocardial infarction within the past year\r\n* QT prolongation, defined as pretreatment corrected QT interval (QTc) > 440 msec in males or > 460 msec in femalesXx_NEWLINE_xXSerious ventricular arrhythmias or high risk for arrhythmias, due to prolongation of the QT-interval (> 60 milliseconds [msec])Xx_NEWLINE_xXEvidence of QT prolongation on pretreatment electrocardiogram (ECG) (greater than 440 ms in males or greater than 450 ms in females)Xx_NEWLINE_xXHas a mean corrected QT interval using Fridericia's Correction Formula (QTcF) prolongation to > 470 ms for females and > 450 ms for males in three successive Screening measurementsXx_NEWLINE_xXHistory of, or at risk for, cardiac disease (e.g., long QT syndrome [> 450 msec] or concurrent treatment with any medication that prolongs QT interval).Xx_NEWLINE_xXHas prolonged corrected QT interval by Fridericia's method (QTcF) at rest, where the mean QTcF interval is > 450 milliseconds (ms) based on triplicate electrocardiograms (ECGs)Xx_NEWLINE_xXMean resting corrected QT interval (QTc), calculated using Fridericia’s formula, > 470 msec obtained from 3 electrocardiograms (ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or torsade de pointes within 12 months of the patient entering in the studyXx_NEWLINE_xXBaseline Fridericia's correction formula (QTcF) or corrected QT (QTc) > 480 ms.; NOTE: This criterion does not apply to patients with a left bundle branch blockXx_NEWLINE_xXCorrected QT (QTc) prolongation > 480 msec, as calculated by either the Bazett or Fridericia formula, as per institutional standardXx_NEWLINE_xX12-lead ECG with QTc interval within defined limitXx_NEWLINE_xXSubject has QTcF interval > 450 msec (average of triplicate determinations based on central reading).Xx_NEWLINE_xXEvidence of QT prolongation on pretreatment electrocardiogram (ECG) (greater than 440 ms in males or greater than 450 ms in females)Xx_NEWLINE_xXA history of clinically significant electrocardiogram (EKG) abnormalities, including QT prolongation, a family history of prolonged QT interval syndrome, or myocardial infarction (MI) less than 1 year ago with ensuing unstable EKGXx_NEWLINE_xXCorrected QT interval (QTc) > 470 msec (as calculated by Fridericia correction formula) at study entry or congenital long QT syndromeXx_NEWLINE_xXPatients with history of long QT syndrome, uncorrectable electrolyte abnormalities, or corrected QT (QTc) > 500 msecXx_NEWLINE_xXHave corrected QT interval of >500 millisecond (msec) on screening electrocardiogram (ECG).Xx_NEWLINE_xXQTc interval <480 millisecond (msec).Xx_NEWLINE_xXProlonged QTc interval defined as greater than 480 ms.Xx_NEWLINE_xXInability to determine the QT interval on ECG, except for patients with evidence of measurable QT interval at the time of CML diagnosis (e.g. prior to first start of TKI treatment) and who have no documented clinical signs of cardiovascular disease and/or clinical signs of conduction abnormality.Xx_NEWLINE_xXQTc > 450 msec on the average of three serial baseline ECG (using the QTcF formula). If QTcF > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-tested for QTc.This exclusion criterion is not applicable for patients with non-measurable QT interval who have evidence of measurable QT interval at the time of CML diagnosis (e.g. prior to first start of TKI treatment) and who have no documented clinical signs of cardiovascular disease and/or clinical signs of conduction abnormality.Xx_NEWLINE_xXSubjects with prolonged QT interval.Xx_NEWLINE_xXQTc prolongation >480 msec.Xx_NEWLINE_xXSubjects with QTc interval > 480ms.Xx_NEWLINE_xXFridericia corrected QT interval (QTcF) >450 milliseconds (msec) (men) or >475 msec (women) on a 12-lead electrocardiogram (ECG) during the Screening period.Xx_NEWLINE_xXHave corrected QT interval of >470 milliseconds on screening electrocardiogram (ECG).Xx_NEWLINE_xXQTcF interval >450 ms for men and >470 ms for women, symptomatic bradycardia <45 beats per minute or other significant ECG abnormalities in the investigator's opinion.Xx_NEWLINE_xXProlongation of corrected QT interval (QTc) to >480 ms as demonstrated by a repeated electrocardiogram (ECG) or a clinically significant ECG abnormality, including a marked prolonged QT/QTc interval (eg, a repeated demonstration of a QTc interval >500 ms).Xx_NEWLINE_xXCongenital long QT syndrome or a corrected QTc interval of ?450 ms at the Screening visit.Xx_NEWLINE_xXQTc > 450 ms (M) or 470 ms (F) (Bazett formula -QT Interval / ? (RR interval) where RR Interval = 60/HR).Xx_NEWLINE_xX