The patient has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, uncontrolled thrombotic or hemorrhagic disorder, or any other serious uncontrolled medical disorder in the opinion of the investigatorXx_NEWLINE_xXPatients with cardiac diseases ongoing or in the past 6 months (e.g. congestive heart failure, acute myocardial infarction, significant uncontrolled arrhythmias) are not eligible for this trialXx_NEWLINE_xXMust have no congenital heart diseaseXx_NEWLINE_xXHistory of congestive heart failureXx_NEWLINE_xXPatients with a known history of congestive heart failure (CHF), cardiomyopathy, myocarditis, myocardial infarction (MI), exposure to cardiotoxic medications, or with a clinical history suggestive of the above must have an electrocardiography (EKG) and echocardiogram (ECHO) performed within 42 days prior to registration and as clinically indicated while on treatmentXx_NEWLINE_xXPatient must have no history of recent myocardial infarction (within three months), uncontrolled congestive heart failure, or uncontrolled cardiac arrhythmiaXx_NEWLINE_xXNo congestive heart failure (CHF) within 182 days of registrationXx_NEWLINE_xXPatients who have a significant history of cardiac disease, i.e., uncontrolled hypertension, unstable angina, congestive heart failure, or uncontrolled arrhythmias within 6 months of registrationXx_NEWLINE_xXHistory of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXPatients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection; examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, unstable spinal cord compression, superior vena cava syndrome, symptomatic congestive heart failure, unstable angina pectoris, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent and would limit compliance with study requirementsXx_NEWLINE_xXSymptomatic cardiac disease, including congestive heart failure, coronary artery disease, and arrhythmiasXx_NEWLINE_xXConcomitant diseases/conditions: Angina, myocardial infarction, congestive heart failure or clinically significant valvular heart disease, arrhythmia, immunodeficiency (including known HIV seropositive), ongoing or treatment-requiring chronic liver disease, active infection, oxygen requirement within two weeks prior to randomization, diffuse interstitial lung disease (ILD) or pulmonary fibrosis, second invasive malignancy treated with chemotherapy and/or radiotherapy, invasive fungal infections requiring systemic treatment within 12 weeks of randomization.Xx_NEWLINE_xXSymptomatic congestive heart failure, unstable angina pectoris, or myocardial infarction within 6 months of registrationXx_NEWLINE_xXHistory of congestive heart failure or myocardial infarction <1 year prior to first study dose administrationXx_NEWLINE_xXActive congestive heart failure or ventricular arrhythmia requiring medicationXx_NEWLINE_xXConcurrent severe or uncontrolled medical disease (i.e., systemic infection, diabetes, hypertension, coronary artery disease, congestive heart failure).Xx_NEWLINE_xXHistory of congestive heart failure, arrhythmias, acute coronary syndrome or torsades de pointesXx_NEWLINE_xXUncontrolled inter-current illness including, but not limited to ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, or serious, uncontrolled cardiac arrhythmia, that might jeopardize the ability of the patient to receive the therapy program outlined in this protocol with reasonable safetyXx_NEWLINE_xXCongestive heart failureXx_NEWLINE_xXUnstable angina.Xx_NEWLINE_xXHas a medical history of myocardial infarction within 6 months, symptomatic congestive heart failureXx_NEWLINE_xXClinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure, or serious cardiac arrhythmia requiring medication.Xx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:\r\n* Symptomatic congestive heart failure of New York heart Association Class III or IV\r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease\r\n* Severely impaired lung function as defined as spirometry and diffusion capacity of the lung for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or oxygen (O2) saturation that is 89% or less at rest on room air\r\n* Uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN\r\n* Active (acute or chronic) or uncontrolled severe infections\r\n* Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitisXx_NEWLINE_xXPatients with known unstable angina pectorisXx_NEWLINE_xXHistory of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXEvidence or history of significant cardiac disease (such as, but not limited to, unstable angina pectoris, myocardial infarction within the prior 6 months, heart failure within 6 months, symptomatic congestive heart failure, symptomatic or uncontrolled arrhythmias, severe aortic stenosis, symptomatic mitral stenosis).Xx_NEWLINE_xXClinically significant cardiovascular disease or peripheral vascular (e.g. myocardial infarction, unstable angina within 6 months of study entry), symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia requiring medications, baseline corrected QT (QTc) > 450 msec or previous history of QT prolongation while taking other medicationsXx_NEWLINE_xXEXCLUSION CRITERIA FOR SECOND-LINE THERAPY: Cardiovascular disease problems including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke within the last 3 months, or a diagnosis of congestive heart failureXx_NEWLINE_xXEXCLUSION CRITERIA FOR THIRD-LINE THERAPY: Cardiovascular disease problems including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke within the last 3 months, or a diagnosis of congestive heart failureXx_NEWLINE_xXClinically significant cardiac diseases, including any of the following:\r\n* Unstable angina pectoris\r\n* Myocardial infarction =< 3 months prior to registration\r\n* Other clinically significant heart disease such as congestive heart failure requiring treatment or uncontrolled hypertensionXx_NEWLINE_xXHistory of active myocardial ischemia, cardiomyopathy, uncontrolled dysrhythmia, or congestive heart failure within the last 6 months before enrollmentXx_NEWLINE_xXImpaired cardiac function including any of the following:\r\n* Myocardial infarction within 6 months of starting study drug\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 anti-hypertensive regimen)Xx_NEWLINE_xXMust not have a serious heart condition, such as congestive heart failure, unstable angina pectoris, or heart attack within the last three monthsXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 monthsXx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:\r\n* Symptomatic congestive heart failure of New York heart Association class III or IV\r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease\r\n* Severely impaired lung function as defined as spirometry and carbon monoxide diffusing capability test (DLCO) that is 50% of the normal predicted value and/or oxygen (O2) saturation that is 89% or less at rest on room air\r\n* Uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN\r\n* Active (acute or chronic) or uncontrolled severe infections\r\n* Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis\r\n* Note: A detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients; hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and hepatitis C virus (HCV) ribonucleic acid (RNA) polymerase chain reaction (PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infectionXx_NEWLINE_xXPatients who have evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months are not eligibleXx_NEWLINE_xXCardiac issues consisting of either symptomatic congestive heart failure (NYHA Class II or higher), unstable angina pectoris, myocardial infarction within 6 months, and/or cardiac arrhythmia, including atrial fibrillation (which is symptomatic or requires treatment).Xx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions such as:\r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to start of everolimus\r\n* Serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease\r\n* Symptomatic congestive heart failure of New York Heart Association class III or IV\r\n* Active (acute or chronic) or uncontrolled severe infection,\r\n* Liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable hepatitis B virus [HBV]-deoxyribonucleic acid [DNA] and/or positive hepatitis B surface antigen [HbsAg], quantifiable hepatitis C virus [HCV]-ribonucleic acid [RNA])\r\n* Known severely impaired lung function (spirometry and diffusion capacity of the lung for carbon monoxide [DLCO] 50% or less of normal and oxygen [O2] saturation 88% or less at rest on room air)\r\n* Active bleeding diathesisXx_NEWLINE_xXNo serious medical conditions such as myocardial infarction within 6 months prior to entry, congestive heart failure, unstable ventricular arrhythmia, uncontrolled hypertension, uncontrolled diabetes mellitus, uncontrolled psychotic disorders, serious infections, active peptic ulcer disease, psychiatric illness, or any other medical conditions that might be aggravated by treatment or limit complianceXx_NEWLINE_xXUnstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac diseaseXx_NEWLINE_xXHistory of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including but not limited to clinically significant cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction, within the past 6 monthsXx_NEWLINE_xXHistory of cerebral vascular event, unstable angina, myocardial infarction, or cardiac symptoms consistent with congestive heart failure within the last 6 monthsXx_NEWLINE_xXHistory of congestive heart failure, unstable angina pectoris, unstable atrial fibrillation, or cardiac arrhythmia.Xx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months; recent history of myocardial infarction in the six months prior to registrationXx_NEWLINE_xXParticipants who have an uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, congestive heart failure-New York Heart Association class III or IV, active ischemic heart disease, myocardial infarction within the previous six months, uncontrolled diabetes mellitus, gastric or duodenal ulceration diagnosed within the previous 6 months, chronic liver or renal disease, or severe malnutrition; in addition, patients are ineligible if they have a psychiatric illness or a social situation that could limit their ability to comply with the study requirementsXx_NEWLINE_xXPatients with cardiac diseases ongoing or in the past 6 months (e.g. congestive heart failure, acute myocardial infarction, significant uncontrolled arrhythmias) are not eligible for this trialXx_NEWLINE_xXTesting for LVEF is not required for pre-registration, but patient must not have a recent LVEF < LLN or have symptoms of congestive heart failureXx_NEWLINE_xXSerious clinically significant illnesses, such as: cardiovascular disease (uncontrolled congestive heart failure, uncontrolled hypertension, cardiac ischemia, myocardial infarction, and severe cardiac arrhythmia), bleeding disorders, symptomatic autoimmune diseases (such as inflammatory bowel disease, autoimmune hepatitis, uncontrolled hypo or hyperthyroidism), severe obstructive or restrictive pulmonary diseases, retinopathy, active systemic infections, and inflammatory bowel disordersXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 monthsXx_NEWLINE_xXThe patient has active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, unstable angina pectoris, or uncontrolled congestive heart failure (NYHA class III and IV).Xx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months; patients experiencing an isolated cardiac complication at the time of transplant who have been evaluated by cardiology and remained stable for at least 60 days are eligibleXx_NEWLINE_xXHistory or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within the previous year.Xx_NEWLINE_xXSymptomatic congestive heart failureXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months; Note: prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevantXx_NEWLINE_xXHistory or evidence of cardiac risk including any of the following: history or evidence of current clinically significant uncontrolled arrhythmias or arrhythmia requiring treatment with the exceptions of atrial fibrillation and paroxysmal supraventricular tachycardia; history of acute coronary syndromes within 6 months prior to the first dose of study therapy (including myocardial infarction and unstable angina, coronary angioplasty, or stenting); history of uncontrolled hypertension; or any history of congestive heart failure with most recent ejection fraction < 45% (screening left ventricular ejection fraction [LVEF] assessment without history of congestive heart failure CHF is not required)Xx_NEWLINE_xXHistory of:\r\n* Symptomatic congestive heart failure\r\n* Unstable angina pectoris or cardiac arrhythmia (subjects with stable atrial fibrillation are not excluded)\r\n* Adrenal insufficiencyXx_NEWLINE_xXHeart failure, ischemic heart disease, uncontrolled hypertension, uncontrolled diabetes mellitus, psychiatric condition, ongoing cardiac arrhythmia requiring medication (Grade ?2, by NCI CTCAE v. 4.03), or significant/unstable concurrent medical illness by investigator opinionXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 monthsXx_NEWLINE_xXAny significant medical diseases or conditions, as assessed by the investigators and sponsor that would substantially increase the medical risks of participating in this study (i.e., uncontrolled diabetes, NYHA II-IV congestive heart failure, myocardial infarction within 6 months of study, severe chronic pulmonary disease or active uncontrolled infection, uncontrolled or clinically relevant pulmonary edema).Xx_NEWLINE_xXUnstable cardiac disease, including unstable angina or unstable hypertension, or need to change medication within 6 weeks of provision of consent due to lack of disease controlXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.Xx_NEWLINE_xXUncontrolled hypertension, unstable angina, congestive heart failure of any NYHA classification stage greater than (>) 2, serious cardiac arrhythmia requiring treatment (exceptions: atrial fibrillation, paroxysmal supraventricular tachycardia), history of myocardial infarction within 6 months of enrollmentXx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions such as:\r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease\r\n* Symptomatic congestive heart failure of New York Heart Association class III or IV\r\n* Active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease\r\n* Known severely impaired lung function\r\n* Corrected QT (QTc) interval > 450 msec for males or > 470 msec for females\r\n* Active, bleeding diathesis\r\n* Psychiatric illness/social situations that would preclude informed consent, limit compliance with study requirementsXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, uncontrolled congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.Xx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 monthsXx_NEWLINE_xXKnown history of coronary artery disease, angina, myocardial infarction, congestive heart failure, cardiac arrhythmia or any other type of heart disease present within the last 6 monthsXx_NEWLINE_xXUnstable angina pectoris,Xx_NEWLINE_xXPatients with a history of myocardial infarction or unstable angina =< 6 months prior to registration or congestive heart failure (CHF) requiring use of ongoing maintenance therapy, or life-threatening ventricular arrhythmiasXx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:\r\n* Symptomatic congestive heart failure of New York Heart Association class III or IV\r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease\r\n* Severely impaired lung function as defined as spirometry and diffusion capacity of the lungs for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or oxygen (O2) saturation that is 90% or less at rest on room air\r\n* Active (acute or chronic) or uncontrolled severe infections\r\n* Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C)Xx_NEWLINE_xXNo unstable angina or myocardial infarction within the prior 6 months; no symptomatic congestive heart failure; no serious cardiac arrhythmia requiring medication; no cerebrovascular ischemia or stroke within the past 6 monthsXx_NEWLINE_xXSubjects with significant or uncontrolled cardiovascular disease (e.g., uncontrolled hypertension, peripheral vascular disease, congestive heart failure, cardiac arrhythmia, or acute coronary syndrome) within 6 months prior to starting study treatment or heart attack within 12 months prior to starting study treatmentXx_NEWLINE_xXUnstable angina pectorisXx_NEWLINE_xXClinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) =< 1 year or serious concurrent infectionXx_NEWLINE_xXUncontrolled angina, congestive heart failure, myocardial infarction (MI) (within last 6 months), congenital long QT syndrome, history of clinically significant ventricular arrhythmia, prolonged QTcF interval on pre-entry electrocardiogram (EKG) (greater than normal range)Xx_NEWLINE_xXHistory of myocardial infarction or decompensated congestive heart failure (CHF) within the last 6 monthsXx_NEWLINE_xXSubjects with evidence of severe or uncontrolled systemic disease, or any concurrent condition, which could compromise participation in the study, including, but not limited to, active or uncontrolled infection, immune deficiencies (human immunodeficiency virus [HIV]-positive subjects on combination antiretroviral therapy are eligible), hepatitis B, hepatitis C, uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 3 months, uncontrolled cardiac arrhythmia, stroke/cerebrovascular accident within the past 3 months, or psychiatric illness/social situations which would jeopardize compliance with the protocolXx_NEWLINE_xXUncontrolled inter-current illness including, but not limited to:\r\n* Ongoing or active infection (requiring IV antibiotics within 2 weeks of study enrollment)\r\n* Symptomatic/uncontrolled congestive heart failure (New York heart association > class II)\r\n* Unstable angina pectoris\r\n* Recent myocardial infarction (< 6 months)\r\n* Uncontrolled cardiac arrhythmia\r\n* Uncontrolled hypertension (? Common Terminology Criteria for Adverse Events [CTCAE] v4.03 grade 3)\r\n* Prior history of hypertensive crisis or hypertensive encephalopathy\r\n* Hemorrhagic or ischemic stroke < 6 months\r\n* Clinically-significant vascular disease (e.g. aortic aneurysm, or dissecting aneurysm), severe aortic stenosis clinically significant peripheral vascular disease, or ? grade 3 cardiac toxicity following prior chemotherapy\r\n* Interstitial lung disease (ILD) \r\n* Active peptic ulcer disease or gastritis interfering with the absorption of rucaparib\r\n* Active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C\r\n* Active varicella zoster infection, cytomegalovirus infection, or history of tuberculosis\r\n* Psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consentXx_NEWLINE_xXUncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, seizuresXx_NEWLINE_xXPatient has significant abnormalities on screening electrocardiogram (EKG) and active and significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, hypertension, valvular disease, pericarditis, or myocardial infarction within 6 months of screeningXx_NEWLINE_xXPresence of uncontrolled hypertension or congestive heart failure, or acute myocardial infarction within 6 months of entryXx_NEWLINE_xXCongestive heart failure (CHF) since axitinib can cause CHFXx_NEWLINE_xXPatients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction within the previous 3 months; coronary angioplasty, or stenting or bypass grafting within the past 6 months; cardiac ventricular arrhythmias requiring medication; any history of second (2nd) or third (3rd) degree atrioventricular conduction defects)Xx_NEWLINE_xXUncontrolled intercurrent illness including current active infection requiring systemic therapy or symptomatic congestive heart failure within 6 monthsXx_NEWLINE_xXCOHORT 1: HORMONE RECEPTOR POSITIVE BREAST CANCER: Known history of cardiac arrhythmias including uncontrolled atrial fibrillation, tachyarrhythmias or bradycardia, history of congestive heart failure, or myocardial infarction or stroke in the previous 3 months will be excludedXx_NEWLINE_xXCOHORT 2: TRIPLE NEGATIVE BREAST CANCER: Known history of cardiac arrhythmias including uncontrolled atrial fibrillation, tachyarrhythmias or bradycardia, history of congestive heart failure, or myocardial infarction or stroke in the previous 3 months will be excludedXx_NEWLINE_xXCOHORT 3: ENDOMETRIAL CANCER: Known history of cardiac arrhythmias including uncontrolled atrial fibrillation, tachyarrhythmias or bradycardia, history of congestive heart failure, or myocardial infarction or stroke in the previous 3 months will be excludedXx_NEWLINE_xXUncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug (e.g. hypocalcemia, hypokalemia, hypomagnesemia)Xx_NEWLINE_xXActive cardiac disease defined as active angina, symptomatic congestive heart failure, or myocardial infarction within the previous 6 monthsXx_NEWLINE_xXHistory of clinically significant cardiac dysfunction, including the following:\r\n* Current unstable angina\r\n* Current symptomatic congestive heart failure of New York Heart Association (NYHA) class 2 or higher.\r\n* Uncontrolled hypertension >= grade 2 (patients with a history hypertension controlled with anti-hypertensives to =< grade 1 are eligible).\r\n* Left ventricular ejection fraction (LVEF) below institutional lower limit of normal (LLN) or below 50%, whichever is lower.\r\n* Uncontrolled arrhythmias.\r\n* Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack within the previous 6 months.Xx_NEWLINE_xXHistory of pulmonary edema or decompensated congestive heart failure with in six (6) week of enrollment.Xx_NEWLINE_xXUnstable angina pectorisXx_NEWLINE_xXHistory of unstable or deteriorating cardiac or pulmonary disease (other than BOS) within the previous 6 months, including but not limited to the following:\r\n* Unstable angina pectoris or myocardial infarction\r\n* Congestive heart failure requiring hospitalization\r\n* Uncontrolled clinically significant arrhythmiasXx_NEWLINE_xXClinically relevant serious co-morbid medical conditions including, but not limited to, active infection, recent (less than or equal to six months) myocardial infarction, unstable angina, symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled cardiac arrhythmias, chronic obstructive or chronic restrictive pulmonary disease, active CNS disease uncontrolled by standard of care, known positive status for human immunodeficiency virus (HIV) and/or active hepatitis B or C, cirrhosis, or psychiatric illness/social situations that would limit compliance with study requirements.Xx_NEWLINE_xXPatients with active renal, cardiac (congestive cardiac failure, myocardial infarction, myocarditis), or pulmonary diseaseXx_NEWLINE_xXHistory or presence of myocardial infarction, clinically relevant valvular heart disease, or congestive heart failure within the last 12 months;Xx_NEWLINE_xXHistory of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXHistory of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: a) Symptomatic congestive heart failure of New York heart Association class III or IV; b) Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease; c) Severely impaired lung function as defined as oxygen (O2) saturation that is 92% or less at rest on room air; d) Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN; e) Systemic fungal, bacterial, viral, or other infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement) despite appropriate antibiotics or other treatment; f) Known active or symptomatic viral hepatitis or chronic liver disease. Uncontrolled adrenal insufficiency.Xx_NEWLINE_xXNo uncontrolled angina, congestive heart failure or myocardial infarction (MI) within 6 monthsXx_NEWLINE_xXUncontrolled intercurrent illness including, but not limited to:\r\n* Malabsorption syndrome significantly affecting gastrointestinal function\r\n* Ongoing or active infection requiring parenteral antibiotics\r\n* Impairment of lung function (chronic obstructive pulmonary disease [COPD] > grade 2, lung conditions requiring oxygen therapy)\r\n* Symptomatic congestive heart failure (class III or IV of the New York Heart Association classification for heart disease)\r\n* Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months\r\n* Clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment [National Cancer Institute -Common Terminology Criteria for Adverse Events, version 4.03, grade 3])\r\n* Fridericia's correction formula (QTcF) >= 480 msec on screening electrocardiography (EKG)\r\n* Known history of clinically significant QT/corrected QT (QTc) prolongation or torsades de pointes (TdP)\r\n* ST depression or elevation of >= 1.5 mm in 2 or more leads\r\n* Diarrhea of any cause >= Common Terminology Criteria for Adverse Events (CTCAE) grade 2\r\n* Psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements including maintenance of a compliance/pill diary\r\n* Symptomatic brain metastases (patients with a history of brain metastases must be clinically stable for more than 4 weeks from completion of radiation treatment and be off steroids)\r\n* Known history of chronic liver or chronic renal failure\r\n* Poor wound healing capacityXx_NEWLINE_xXUncontrolled clinically significant arrhythmia, myocardial ischemia or congestive heart failure within the past 2 weeks, that is considered by the treating physician as a contraindication for initiation of chemotherapy;  discussion with the principal investigator is encouraged if further clarification is requiredXx_NEWLINE_xXClinically significant uncontrolled major cardiac, respiratory, renal, hepatic, gastrointestinal or hematologic disease but not limited to: \r\n*Symptomatic congestive heart failure, unstable angina, or cardiac dysrhythmia not controlled by pacer device.Xx_NEWLINE_xXSymptoms of congestive heart failure or uncontrolled cardiac rhythm disturbanceXx_NEWLINE_xXCardiovascular disease problems including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke, or congestive heart failure within the last 6 monthsXx_NEWLINE_xXHistory of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xX(Bevacizumab-related exclusion) Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents =< 6 months prior to study enrolment, myocardial infarction =< 6 months prior to study enrollment, unstable angina, grade II or greater congestive heart failure, or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatmentXx_NEWLINE_xXClinically significant uncontrolled major cardiac, respiratory, renal, hepatic, gastrointestinal or hematologic disease but not limited to: \r\n* a) Symptomatic congestive heart failure, unstable angina, or cardiac dysrhythmia not controlled by pacer device \r\n* b) No myocardial infarction within 3 months of registrationXx_NEWLINE_xXPatient has history of uncontrolled angina, congestive heart failure or recent myocardial infarction (MI) within 6 monthsXx_NEWLINE_xXAbsence of unstable cardiac disease defined as myocardial infarction with 6 months, uncontrolled heart failure, or uncontrolled cardiac arrhythmiaXx_NEWLINE_xXHistory of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXHistory of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXFree of symptoms of uncontrolled cardiac disease including unstable angina, decompensated congestive heart failure, or arrhythmia; the ejection fraction by gated cardiac blood flow scan (MUGA) or echocardiogram must be > 40%Xx_NEWLINE_xXUncontrolled intercurrent illness including, but not limited to: \r\n* Ongoing or active infections\r\n* Cardiac conditions, such as:\r\n** Symptomatic congestive heart failure\r\n** Uncontrolled hypertension\r\n** Unstable angina pectoris\r\n** Cardiac arrhythmia\r\n* Active peptic ulcer disease or gastritis\r\n* History of inflammatory bowel disease, ulcerative colitis or Crohn’s disease\r\n* Active bleeding diatheses\r\n* Any subject known to have evidence of acute or chronic hepatitis B or hepatitis C. Patients will undetectable levels of virus will be allowed to participate\r\n* Any subject known to have evidence of human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS)\r\n* Uncontrolled seizuresXx_NEWLINE_xXPresence of any serious concomitant systemic disorders incompatible with the study in the opinion of the investigator (e.g., uncontrolled congestive heart failure, active infection, etc.);Xx_NEWLINE_xXAny severe or concurrent disease or condition including uncontrolled systemic infection, congestive heart failure, angina pectoris or cardiac arrhythmia and autoimmune processes that in the opinion of the investigator would make the patient inappropriate for study participationXx_NEWLINE_xXActive uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of >= 2; including individuals who currently use digitalis, beta-blockers, or calcium channel blockers specifically for congestive heart failure), unstable angina, myocardial infarction within 12 months of enrollment, or ventricular arrhythmiaXx_NEWLINE_xXHave significant, uncontrolled or active cardiovascular disease, specifically including but restricted to:\r\n* Myocardial infarction (MI) within 6 months of trial enrollment\r\n* Unstable angina within 6 months of trial enrollment\r\n* Congestive heart failure (CHF) with 6 months prior to trial enrollment\r\n* Any history of ventricular arrhythmia\r\n* Cerebrovascular accident or transient ischemic attack within 6 months of D1 of treatment\r\n* Clinically significant atrial arrhythmia or severe baseline bradycardia defined as resting heart rate < 50 beat per minute\r\n* Uncontrolled hypertension defined as baseline systolic blood pressure (SBP) > 160 and diastolic blood pressure (DBP) > 100 on 3 separate clinic visits or past history of hypertensive urgency, emergency or encephalopathyXx_NEWLINE_xXPatients with history of congestive heart failure stage III or greaterXx_NEWLINE_xXUncontrolled inter-current illness including, but not limited to ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, or serious, uncontrolled cardiac arrhythmia, that might jeopardize the ability of the patient to receive the therapy program outlined in this protocol with reasonable safetyXx_NEWLINE_xXUncontrolled intercurrent illness including active infection requiring systemic therapy or symptomatic congestive heart failure within 6 monthsXx_NEWLINE_xXActive cardiac disease defined as active angina, symptomatic congestive heart failure, or myocardial infarction within previous six monthsXx_NEWLINE_xXSubjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, severe, uncontrolled hypertension (systolic >150/diastolic > 100 mmHg) or other symptoms of catecholamine excess after efforts to achieve adequate alpha blockade then beta blockadeXx_NEWLINE_xXHeart failure that in the opinion of the investigator is on the basis of ischemic heart disease (eg, prior myocardial infarction with documented history of cardiac enzyme elevation and electrocardiogram [ECG] changes) or uncorrected valvular disease and not primarily due to AL amyloid cardiomyopathyXx_NEWLINE_xXFor participants with congestive heart failure, cardiovascular-related hospitalizations within 4 weeks prior to randomizationXx_NEWLINE_xXPatients with clinically significant cardiac disease including one of the following currently or in the previous 6 months: myocardial infarction, unstable cardiac function due to unstable angina or congestive heart failure, congenital long QT syndrome, torsades de pointes or significant ventricular arrhythmias .Xx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial infarction =< 6 months; Note: Prior to entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevantXx_NEWLINE_xXOther serious illness or medical condition within 6 months before enrollment, including any of the following: Concurrent congestive heart failure NYHA Class III or IV, severe/unstable angina pectoris, myocardial infarction, uncontrolled hypertension, coronary/peripheral artery bypass graft, high-risk uncontrolled arrhythmias, stroke.Xx_NEWLINE_xXAny life-threatening illness, medical condition, or organ system dysfunction, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active autoimmune disorder, or psychiatric illness/social situations that, in the investigator’s opinion, could compromise the subject’s safety or put the study outcomes at undue risk; currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollmentXx_NEWLINE_xXMyocardial infarction (MI) < 6 months, congestive heart failure (CHF), unstable angina, active cardiomyopathy, unstable ventricular arrhythmiaXx_NEWLINE_xXHas significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension, uncontrolled arrhythmias, or severe valvular heart disease, or a myocardial infarction within 6 months prior to the first dose of study treatmentXx_NEWLINE_xXSubjects must not have a known history of congestive heart failure, unstable angina pectoris, or cardiac arrhythmia (with the exception of chronic and rate-controlled atrial fibrillation)Xx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 monthsXx_NEWLINE_xXPatients must have no fever or evidence of infection or other coexisting medical condition that would preclude administration of study drugs; patients with uncontrolled congestive heart failure, unstable angina and myocardial infarction within 3 months will be excludedXx_NEWLINE_xXUnstable cardiac disease, including unstable angina or unstable hypertension, as defined by the need for change in medication for lack of disease control within the last three monthsXx_NEWLINE_xXHistory of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 monthsXx_NEWLINE_xXPatients with history of congestive heart failure stage III or greaterXx_NEWLINE_xXPatients with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:\r\n* Clinically significant cardiac diseases, including any of the following:\r\n** History or presence of serious uncontrolled ventricular arrhythmias \r\n** Clinically significant resting bradycardia\r\n** Any of the following within 3 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, coronary artery bypass graft (CABG), congestive heart failure (CHF), cerebrovascular accident (CVA), transient ischemic attack (TIA), pulmonary embolism (PE)\r\n** Uncontrolled hypertension defined by a systolic blood pressure (SBP) ? 160 mmHg and/or diastolic blood pressure (DBP) ? 100 mm Hg, with or without anti-hypertensive medication(s)\r\n* Cirrhosis, chronic active hepatitis or chronic persistent hepatitis\r\n* Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)\r\n* Known diagnosis of any condition (i.e. post-hematopoietic or organ transplant, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, etc.) that requires chronic immunosuppressive therapy; usage of non-steroidal anti-inflammatory medications (NSAIDS) for the treatment of osteoarthritis and uric acid synthesis inhibitors for the treatment of gout are permitted; for questions, please consult the study chair\r\n* Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocolXx_NEWLINE_xXPatients with uncontrolled cardiovascular disease (a history of hospitalization for acute myocardial infarction, arrhythmia, or congestive heart failure within 3 months prior to registration) will be excludedXx_NEWLINE_xXUncontrolled concurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmiaXx_NEWLINE_xXHas history of myocardial infarction having occurred less than 6 months before inclusion, any known uncontrolled arrhythmia, symptomatic angina pectoris, active ischemia, or cardiac failure not controlled by medications; patients with coronary artery disease (CAD) recently treated with surgery and/or stent, if stable without symptomatic angina pectoris, active ischemia are eligibleXx_NEWLINE_xXNo uncontrolled angina, congestive heart failure or myocardial infraction (MI) within 6 months prior to registration on studyXx_NEWLINE_xXUncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, cardiac dysfunction, unstable angina pectoris, cardiac arrhythmia, prolonged QTc, interstitial lung disease, gastrointestinal perforation, hepatic impairment/failure, or renal impairment/failureXx_NEWLINE_xXCardiovascular disease: history of congestive heart failure, myocardial infarction within the 6 months of study entry, symptomatic cardiac arrhythmia requiring treatmentXx_NEWLINE_xXCardiac:\r\n* History of clinically significant cardiac dysfunction, including the following:\r\n** Current unstable angina\r\n** Current symptomatic congestive heart failure of New York Heart Association (NYHA) class 2 or higher\r\n** History of congenital long QT syndrome or mean corrected QT Fridericia’s formula (QTcF) > 450 msec at baseline or uncorrectable electrolyte abnormalities\r\n** Uncontrolled hypertension >= grade 3 (patients with a history of hypertension controlled with anti-hypertensives to =< grade 1 and patients with hypertension grade 2 that have treating physician approval of safety, are eligible)\r\n** Left ventricular ejection fraction (LVEF) below institutional lower limit of normal (LLN) or below 40%, whichever is lower\r\n** Uncontrolled arrhythmias\r\n** Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack within the previous 6 months \r\nNote: Optional tumor biopsies (punch, fine-needle aspiration [FNA], core or excisional) at pre-treatment, week 1, and at progression will be presented to subjects considering this study; additional optional tumor biopsies may also be offered if deemed appropriate by principal investigator; additional subjects at the MTD/RP2D expansion cohort are required to have correlative studies (blood collection and tumor biopsies at the defined time points)Xx_NEWLINE_xXActive cardiac disease defined as active angina, symptomatic congestive heart failure, or myocardial infarction within previous six monthsXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction =< 6 months prior to registrationXx_NEWLINE_xXUncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, renal failure, cardiac arrhythmia, interstitial lung disease, hepatic failure / hepatorenal syndrome, gastrointestinal (GI) perforation, cerebrovascular event, microangiopathic hemolytic anemia, corneal perforation/ulceration, or documented hepatitis B virus infectionXx_NEWLINE_xXUncontrolled intercurrent illness including symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia and myocardial infarction (MI) within 3 months of initiation of therapyXx_NEWLINE_xXHistory of clinically significant cardiac dysfunction, unless deemed to be direct result of disease, including the following:\r\n* Current unstable angina\r\n* Symptomatic congestive heart failure of New York Heart Association (NYHA) class 2 or higher\r\n* Uncontrolled hypertension > grade 2 (patients with history of hypertension controlled with anti-hypertensives to =< grade 2 are eligible\r\n* Left ventricular ejection fraction (LVEF) below institutional lower limit of normal or below 50%\r\n* Uncontrolled arrhythmias\r\n* Myocardial infraction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack within the previous 6 monthsXx_NEWLINE_xXUnstable angina and/or symptomatic congestive heart failure requiring hospitalization within the last 6 months; transmural myocardial infarction within the last 6 months prior to study entryXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 monthsXx_NEWLINE_xXThe subject has uncontrolled intercurrent illness including, but not limited to:\r\n* Ongoing or active infection\r\n* Diabetes mellitus\r\n* Symptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 12 months of screeningXx_NEWLINE_xXSymptomatic valvular heart diseaseXx_NEWLINE_xXSubjects with uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure, myocardial infarction within the past 6 months or serious uncontrolled cardiac arrhythmia are not eligibleXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 monthsXx_NEWLINE_xXSymptomatic ischemia, unstable angina pectorisXx_NEWLINE_xXUncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; examples of uncontrolled medical conditions include:\r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease\r\n* Symptomatic congestive heart failure of New York Heart Association class III or IV\r\n* Active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis (i.e. quantifiable Hepatitis B virus [HBV]-deoxyribonucleic acid [DNA] and/or positive Hepatitis B surface antibody [HbsAg], quantifiable Hepatitis C virus [HCV]-ribonucleic acid [RNA])\r\n* Known severely impaired lung function (spirometry and diffusing capacity of the lungs for carbon monoxide (DLCO) 50% or less of normal and O2 saturation 88% or less at rest on room air)\r\n* Active, bleeding diathesisXx_NEWLINE_xXActive or unstable cardiac disease or heart attack within 3 months of starting study treatmentXx_NEWLINE_xXHas known current symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmiaXx_NEWLINE_xXHistory of myocardial infarction =< 180 days prior to registration or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXHas cardiovascular impairment, history of congestive heart failure greater than NYHA Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months prior to the planned first dose of tazemetostat; or ventricular cardiac arrhythmia requiring medical treatmentXx_NEWLINE_xXHistory of heart failure or cardiac arrhythmiaXx_NEWLINE_xXSubjects with evidence of severe or uncontrolled systemic disease, or any concurrent condition, which could compromise participation in the study, including, but not limited to, active or uncontrolled infection, immune deficiencies, hepatitis B, hepatitis C, uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia, stroke/cerebrovascular accident within the past 6 months, or psychiatric illness/social situations which would jeopardize compliance with the protocolXx_NEWLINE_xXActive heart disease including symptomatic coronary artery disease, uncontrolled arrhythmias, or symptomatic congestive heart failureXx_NEWLINE_xXHistory of congestive heart failure, symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarctionXx_NEWLINE_xXClinically significant uncontrolled condition(s) including but not limited to: active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia (subjects with stable atrial fibrillation are not excluded), history of adrenal insufficiencyXx_NEWLINE_xXSevere/unstable anginaXx_NEWLINE_xXSymptomatic congestive heart failureXx_NEWLINE_xXKnown or suspected congestive heart failure, angina pectoris requiring antianginal medication, or other clinically significant cardiac conditionXx_NEWLINE_xXActive cardiovascular disease including myocardial infarction (MI) < 6 months of screening, symptomatic coronary artery disease (CAD), arrhythmias, hypertension, or heart failure not controlled by medication.Xx_NEWLINE_xXPatients must not have a history of myocardial infarction, severe or unstable angina, clinically significant peripheral vascular disease, grade 2 or greater heart failure, or serious and inadequately controlled cardiac arrhythmiaXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 monthsXx_NEWLINE_xXHistory of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, cardiac arrhythmias, or congestive heart failure, and unstable angina or myocardial infarction within the past 6 monthsXx_NEWLINE_xXPatients with history of congestive heart failure are excludedXx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:\r\n* Symptomatic congestive heart failure of New York Heart Association class III or IV\r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months prior to registration, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease\r\n* Severely impaired lung function as defined as spirometry and diffusion capacity of carbon monoxide (DLCO) that is less than 50% of the normal predicted value and/or oxygen (O2) saturation that is 88% or less at rest on room air\r\n* Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN (Note: optimal glycemic control should be achieved before starting everolimus)\r\n* Active (acute or chronic) or uncontrolled severe infectionsXx_NEWLINE_xXSymptomatic heart disease including but not limited to symptomatic congestive heart failure, symptomatic coronary artery disease, symptomatic angina pectoris, symptomatic myocardial infarction or symptomatic congestive heart failureXx_NEWLINE_xXSerious concomitant illness including but not limited to: uncontrolled cardiac arrhythmias, unstable angina pectoris, uncontrolled congestive heart failure, uncontrolled arterial hypertension, uncontrolled diabetes mellitus, dementia, active infection (including human immunodeficiency virus [HIV] infection) requiring IV or oral antibiotics and psychiatric illnessXx_NEWLINE_xXActive heart disease including but not limited to symptomatic congestive heart failure, symptomatic coronary artery disease, symptomatic angina pectoris, symptomatic myocardial infarction or symptomatic congestive heart failureXx_NEWLINE_xXUnstable angina and/or congestive heart failure requiring hospitalization within the last 6 monthsXx_NEWLINE_xXPatients with class III or greater congestive heart failure (CHF) or myocardial infarction (MI) within last 6 monthsXx_NEWLINE_xXSevere and/or uncontrolled medical disease (i.e., uncontrolled diabetes, congestive heart failure, myocardial infarction within 6 months of study, chronic renal disease, chronic pulmonary disease or active uncontrolled infection)Xx_NEWLINE_xXSubject with significant congestive heart failure (CHF) or history of CHF, chronic renal failure, hepatic failure, neuropathyXx_NEWLINE_xXHave serious medical illnesses including, but not limited to, congestive heart failure, myocardial infarction or cerebral vascular accident within the last six months, or life threatening cardiac arrhythmias.Xx_NEWLINE_xXActive heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease or heart block, or uncontrolled congestive heart failureXx_NEWLINE_xXSevere or uncontrolled, concurrent medical disease (e.g. uncontrolled diabetes, unstable angina, myocardial infarction within 6 months, congestive heart failure, etc.)Xx_NEWLINE_xXSignificant history of a medical problem or co-morbidity that would preclude the patient from undergoing a major abdominal operation such as a history of severe congestive heart failure or active ischemic heart diseaseXx_NEWLINE_xXCardiac disease ongoing or in the past 6 months (e.g. congestive heart failure, acute myocardial infarction, significant uncontrolled arrhythmias)Xx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions such as:\r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease\r\n* Symptomatic congestive heart failure of New York heart Association class III or IV\r\n* Active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable hepatitis B virus [HBV]-deoxyribonucleic acid [DNA] and/or positive hepatitis B virus surface antigen [HbsAg], quantifiable hepatitis C virus [HCV]-ribonucleic acid [RNA])\r\n* Known severely impaired lung function (spirometry and diffusing capacity of the lung for carbon monoxide [DLCO] 50% or less of normal and oxygen [O2] saturation 88% or less at rest on room air)\r\n* Active, bleeding diathesisXx_NEWLINE_xXCardiac disease: symptomatic congestive heart failure or radionuclide ventriculography (RVG), active angina pectoris, or uncontrolled hypertensionXx_NEWLINE_xXPatients with severe or uncontrolled concurrent medical disease (eg. uncontrolled diabetes, unstable angina, myocardial infarction within 6 months, congestive heart failure, etc.)Xx_NEWLINE_xXuncontrolled or severe cardiovascular disease, including recent (<6 months) myocardial infarction or congestive heart failure,Xx_NEWLINE_xXPrevious hospitalization due to documented heart failure in the last 12 monthsXx_NEWLINE_xXUncontrolled hypertension, blood pressure of > 150 mmHg systolic and > 100 mmHg diastolic, or history of hypertensive encephalopathy; subjects with any known uncontrolled inter-current illness including ongoing or active infection, symptomatic congestive heart failure (New York Heart Association [NYHA] grade [Gr.] 2 or >), myocardial infarction, unstable angina pectoris within the past 12 monthsXx_NEWLINE_xXUnstable anginaXx_NEWLINE_xXPatients with any other known disease concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, cardiovascular disease including congestive heart failure, myocardial infarction within 6 months and poorly controlled hypertension, chronic renal disease, or active uncontrolled infection) which could compromise participation in the study. Patients with current active malignancies or any remission for < 6 months, except patients with carcinoma in situ or with non-melanoma skin cancer who may have active disease or be in remission for less than 6 months.Xx_NEWLINE_xXPatients with uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure, myocardial infarction within the past 6 months or serious uncontrolled cardiac arrhythmia are not eligibleXx_NEWLINE_xXCongestive heart failure < 6 months prior to screeningXx_NEWLINE_xXUnstable angina pectoris < 6 months prior to screeningXx_NEWLINE_xXActive heart disease including but not limited to symptomatic congestive heart failure, symptomatic coronary artery disease, symptomatic angina pectoris, symptomatic myocardial infarction, or symptomatic congestive heart failure; also patients with a history of myocardial infarction that is < 1 year prior to registration, or patients with previous congestive heart failure (< 1 year prior to registration) requiring pharmacologic support or with left ventricular ejection fraction < 50%Xx_NEWLINE_xXAny of the following concurrent severe and/or uncontrolled medical conditions:\r\n* Hypertension, labile hypertension, or history of poor compliance with antihypertensive medication\r\n* Angina pectoris\r\n* History of congestive heart failure =< 3 months, unless ejection fraction > 40%\r\n* Myocardial infarction =< 6 months prior to registration\r\n* Cardiac arrhythmia\r\n* Poorly controlled diabetes\r\n* Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung\r\n* Active or recent history of hemoptysis; if hemoptysis has resolved with measures such as palliative radiation therapy (e.g. 3000 cGy over 10 fractions), arteriographic embolization or endobronchial interventions (e.g. photodynamic therapy, brachytherapy), etc. for > 14 days, patients may be considered for participation in this study\r\n* >= Grade 2 hypertriglyceridemia\r\n* >= Grade 2 hypercholesterolemia\r\n* Any illness that in the opinion of the investigator would compromise the ability of the patient to participate safely in the clinical trialXx_NEWLINE_xXSymptomatic congestive heart failure, unstable angina, or unstable cardiac arrhythmiaXx_NEWLINE_xXClinically significant and uncontrolled major cardiac, respiratory, renal, hepatic, gastrointestinal, hematologic or neurological/psychiatric disease or disorder, including but not limited to:\r\n* Active uncontrolled infection\r\n* Symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia\r\n* Any other illness condition(s) that could exacerbate potential toxicities, confound safety assessments, require excluded therapy for management, or limit compliance with study requirements; questions regarding inclusion of individual subjects should be directed to the principal investigator (PI)Xx_NEWLINE_xXPresence of a symptomatic bradyarrhythmia or uncompensated heart failureXx_NEWLINE_xXCongestive heart failure, clinically significant cardiac arrhythmia, history or current evidence of a myocardial infarction during the last 6 months, and/or a current electrocardiogram (ECG) tracing that is abnormal in the opinion of the treating Investigator, or unstable anginaXx_NEWLINE_xXClinically significant uncontrolled major cardiac, respiratory, renal, hepatic, gastrointestinal or hematologic disease but not limited to:\r\n* Active uncontrolled infection\r\n* Symptomatic congestive heart failure, unstable angina, or cardiac dysrhythmia not controlled by pacer device\r\n* No myocardial infarction within 3 months of registrationXx_NEWLINE_xXCardiovascular disease problems including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke, or congestive heart failure within the last 6 monthsXx_NEWLINE_xXCongestive heart disease not controlled by medication.Xx_NEWLINE_xXMedical illness unrelated to MCL within the prior one month that will preclude administration of chemotherapy safely; this includes patients with uncontrolled infection, chronic renal insufficiency, myocardial infarction within the past 6 months, unstable angina, active congestive heart failure, cardiac arrhythmias other than chronic atrial fibrillation and chronic active or persistent hepatitisXx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: symptomatic congestive heart failure of New York heart Association class III or IV unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug or any other clinically significant cardiac disease severely impaired lung function as defined as spirometry and diffusing capacity of the lungs for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or oxygen (O2) saturation that is 88% or less at rest on room air uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN, active (acute or chronic) or uncontrolled severe infections, liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitisXx_NEWLINE_xXCongestive heart failure (CHF) within 6 months prior to first dose;Xx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months; Note: prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevantXx_NEWLINE_xXSymptomatic cardiovascular disease, including but not limited to significant coronary artery disease (e.g., requiring angioplasty or stenting) or congestive heart failure within the preceding 12 monthsXx_NEWLINE_xXHistory of relevant coronary heart disease or myocardial infarction within last 3 years, NYHA Grade III or greater congestive heart failure, cerebro-vascular attack within the prior year, or serious cardiac arrhythmia requiring medication except atrial fibrillation.Xx_NEWLINE_xXNo acute congestive heart failureXx_NEWLINE_xXPatients with serious uncontrolled cardiopulmonary disorders, including congestive heart failure, symptomatic coronary artery disease, serious cardiac arrhythmia, and symptomatic chronic obstructive pulmonary disease or patients with other serious uncontrolled medical diseases; at the discretion of the treating physician, patients who show disease control for at least 6 months may be enrolledXx_NEWLINE_xXPatients who have a history of congestive heart failure, coronary artery disease and myocardial infarction; active or unstable cardiovascular disease or cardiac disease requiring drug or device interventionXx_NEWLINE_xXPatient has severe or uncontrolled concurrent medical disease (e.g. uncontrolled diabetes, unstable angina, myocardial infarction within 6 months, congestive heart failure, etc.)Xx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:\r\n* Symptomatic congestive heart failure of New York Heart Association class III or IV\r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease\r\n* Severely impaired lung function as defined as spirometry and DLCO (diffusing capacity of the lung for carbon monoxide) that is 50% of the normal predicted value and/or oxygen (O2) saturation that is 88% or less at rest on room air\r\n* Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN (Note: optimal glycemic control should be achieved before starting trial therapy)\r\n* Active (acute or chronic) or uncontrolled severe infections\r\n* Liver disease such as hepatitis B/C, cirrhosis or severe hepatic impairment (Child-Pugh class C)\r\n* Blood test indicates hepatitis B/C (Hep B/C) positive or human immunodeficiency virus (HIV) positive\r\n* Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)\r\n* Patients with an active, bleeding diathesis\r\n* Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using 2 effective and reliable birth control methods; adequate protection must be used throughout the trial and for 8 weeks after the last dose of study drug, by both sexes; (women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of everolimus)\r\n* Male patient whose sexual partner(s) are women of child-bearing potential who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment\r\n* Patients who have received prior treatment with a mammalian target of rapamycin (mTOR) inhibitor (e.g., sirolimus, temsirolimus, everolimus)\r\n* Patients with a known hypersensitivity to everolimus or other rapamycins (e.g., sirolimus, temsirolimus) or to its excipients\r\n* History of noncompliance to medical regimens\r\n* Patients unwilling to or unable to comply with the protocolXx_NEWLINE_xXSignificant associated diseases including documented human immunodeficiency virus (HIV) infection, uncontrolled hypertension (diastolic blood pressures > 95%ile for age), unstable angina, congestive heart failure (> New York [NY] class II), poorly controlled diabetes (hemoglobin A1c [Hgb A1c] > 7%), coronary angioplasty within 6 months, myocardial infarction within the last 6 months, or uncontrolled atrial or ventricular cardiac arrhythmia, abnormal coagulation, persistent abnormal urinalysis reflecting intrinsic renal diseaseXx_NEWLINE_xXOther concurrent severe and/or uncontrolled medical disease which could compromise participation in the study; examples include, but are not limited to: \r\n* Uncontrolled diabetes defined as fasting serum glucose > 1.5 x ULN\r\n* Uncontrolled hypertension, or greater than 150/100 in spite of antihypertensive therapy\r\n* Active (acute or chronic) or uncontrolled severe infection\r\n* Unstable angina pectoris, symptomatic congestive heart failure (New York Heart Association Class III or IV), ventricular arrhythmias, active ischemic heart disease, myocardial infarction within six months\r\n* Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitisXx_NEWLINE_xXUnstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia, or need for antiarrhythmic medication for which inability to take an oral preparation of regular medication for 48 hours would represent an unacceptable riskXx_NEWLINE_xXPatient has severe or uncontrolled concurrent medical disease (e.g. uncontrolled diabetes, unstable angina, myocardial infarction within 6 months, congestive heart failure, etc.)Xx_NEWLINE_xXUncontrolled congestive heart failure or anginaXx_NEWLINE_xXPatients must be free of symptoms of uncontrolled cardiac disease including unstable angina, decompensated congestive heart failure, or arrhythmiaXx_NEWLINE_xXNo active infection, symptomatic congestive heart failure (CHF), unstable angina, uncontrolled cardiac arrhythmia and psychiatric disorderXx_NEWLINE_xXSignificant cardiac disease (i.e. uncontrolled high blood pressure, unstable angina, congestive heart failure, myocardial infarction within the previous year) or serious cardiac arrhythmia requiring medication.Xx_NEWLINE_xXSubjects with uncontrolled (over the last 30 days) clinically significant confounding medical conditions such as congestive heart failureXx_NEWLINE_xXCurrent clinical heart failure or symptomatic ischemic heart diseaseXx_NEWLINE_xXPatients with a history of coronary artery disease with angina pectoris, or a history of congestive heart failure will not be eligible to receive DA-EPOCH-R chemotherapyXx_NEWLINE_xXHistory of myocardial infarction =< 6 months, or current symptomatic congestive heart failure or left ventricular ejection fraction (LVEF) < 40% or with > grade 2 diastolic dysfunction, with no symptoms or signs of heart failureXx_NEWLINE_xXUnstable angina (symptoms of angina at rest) or new-onset angina (within last 3 months before randomization)Xx_NEWLINE_xXCardiac disease (NYHA classes II-IV) including myocardial infarction within 6 months before enrollment, or unstable angina, congestive heart failure, or cardiac arrhythmia requiring treatment.Xx_NEWLINE_xXSignificant cardiovascular disease including Congestive Heart Failure or poorly controlled hypertension.Xx_NEWLINE_xXUncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, interstitial lung disease, pneumonitis, active peptic ulcer disease or gastritis, active bleeding diatheses, or serious chronic gastrointestinal conditions associated with diarrheaXx_NEWLINE_xXSymptomatic congestive heart failure, unstable angina pectoris, or myocardial infarction within 6 months of enrollmentXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.Xx_NEWLINE_xXUnstable heart failure defined as emergency hospitalization for worsening, or decompensated heart failure, or syncopal episode within 1 month of screening. Implantable cardiac defibrillator (ICD) or permanent pacemaker (PPM) at screeningXx_NEWLINE_xXUnstable angina or new-onset anginaXx_NEWLINE_xXMust not have a serious heart condition, such as congestive heart failure, unstable angina pectoris, or heart attack within the last three monthsXx_NEWLINE_xXSevere or unstable medical conditions such as heart failure, ischemic heart disease, uncontrolled hypertension, uncontrolled diabetes mellitus, psychiatric condition, as well as an ongoing cardiac arrhythmia requiring medication (? Grade 2, according to NCI CTCAE v4.0) or any other significant or unstable concurrent medical illness that in the opinion of the Investigator would preclude protocol therapy.Xx_NEWLINE_xXActive infection, congestive heart failure, unstable angina, serious cardiac arrhythmias, psychiatric illness, difficult social situations not permitting reliable participation, active bleedingXx_NEWLINE_xXUnstable angina pectoris on medicationXx_NEWLINE_xXCongestive heart failure requiring medication (other than diuretic)Xx_NEWLINE_xXUncontrolled ischemic heart disease, or uncontrolled symptomatic congestive heart failureXx_NEWLINE_xXHistory of cardiac disease: congestive heart failure>NYHA Class 2 or uncontrolled hypertensionXx_NEWLINE_xXUnstable hemodynamic status including: i. Documented myocardial infarction within six months of enrollment. ii.Symptomatic coronary artery stenosis. iii. Congestive heart disease requiring medication. iv. Anti-arrhythmic drug medication. v. Cardiac pacemaker. vi. Severe hypertension (diastolic BP > 100 on medication).Xx_NEWLINE_xXClinically significant (active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months prior to study enrollment; unstable angina, congestive heart failure or a serious cardiac arrhythmia requiring medication.Xx_NEWLINE_xXConcurrent severe and/or uncontrolled medical conditions which could compromise participation in the study such as unstable angina, myocardial infarction within 6 months, unstable symptomatic arrhythmia, symptomatic congestive heart failure, uncontrolled diabetes, serious active, uncontrolled infection after inadequate biliary drainage if tumor obstructing bile duct, or psychiatric illness/social situations.Xx_NEWLINE_xXORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Symptomatic cardiopulmonary disease (including congestive heart failure and hypertension), coronary artery disease, serious arrhythmia or chronic lung disease; patients with these conditions who are stable with relatively minor symptoms and who are appropriate candidates for surgical treatment of their tumor need not be excludedXx_NEWLINE_xXHPV-ASSOCIATED OROPHARYNX SQUAMOUS CELL CARCINOMA: Symptomatic cardiopulmonary disease (including congestive heart failure and hypertension), coronary artery disease, serious arrhythmia or chronic lung disease; patients with these conditions who are stable with relatively minor symptoms and who are appropriate candidates for surgical treatment of their tumor need not be excludedXx_NEWLINE_xXAny unstable, serious co-existing medical conditions including but not limited to myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure, or cerebrovascular accident within twelve (12) months prior to screeningXx_NEWLINE_xXHistory of myocardial infarction ? 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, serious cardiac arrhythmia requiring medication (other than adequately rate-controlled atrial fibrillation), symptomatic congestive heart failure, unstable angina, stroke/transient ischemic attack (TIA) within the past 6 months or myocardial infarction within the past 6 monthsXx_NEWLINE_xXActive cardiac disease defined as unstable angina, uncontrolled hypertension, myocardial infarction in the last six months (unless successfully treated with coronary artery bypass grafting [CABG] or percutaneous transluminal coronary angioplasty [PTCA]), uncontrolled arrhythmia, or symptomatic congestive heart failure; > 3 heart-related hospitalizations in the past yearXx_NEWLINE_xXCardiovascular disease including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke, or congestive heart failure within the last 6 monthsXx_NEWLINE_xXActive including but not limited to symptomatic congestive heart failure, symptomatic coronary artery disease, symptomatic angina pectoris, or symptomatic myocardial infarctionXx_NEWLINE_xXHistory of myocardial infarction =< 180 days (6 months), or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXPatients who have other medical conditions that would contraindicate treatment with aggressive chemotherapy (including active infection, uncontrolled hypertension, congestive heart failure, unstable angina pectoris, or myocardial infarction within the past 6 months, uncontrolled arrhythmia, severe pulmonary disease or requirement of supplemental oxygen)Xx_NEWLINE_xXActive ischemic heart disease or congestive heart failureXx_NEWLINE_xXSubjects with clinically significant active ischemic heart disease, cardiac muscle disease (including cardiomyopathy or congestive heart failure) or myodegenerative disorders that may affect safe study participationXx_NEWLINE_xXPatients will be ineligible for treatment on this protocol if (prior to protocol entry):\r\n* There is a history of a recent (within one year) myocardial infarction\r\n* There is a current or prior history of angina/coronary symptoms requiring medications and/or evidence of depressed left ventricular function (LVEF < 45% by MUGA or ECHO)\r\n* There is clinical evidence of congestive heart failure requiring medical management (irrespective of MUGA or ECHO results)Xx_NEWLINE_xXAny severe or uncontrolled medical condition or other condition that could affect participation in this study, including: unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction =< 6 months prior to study entryXx_NEWLINE_xXA significant history or current evidence of cardiac disease including, but not limited to: congestive heart failure, coronary artery disease, angina pectoris, uncontrolled hypertension, serious arrhythmias or myocardial infarction within the previous six monthsXx_NEWLINE_xXCurrent unstable angina.Xx_NEWLINE_xXUnstable angina and/or congestive heart failure requiring hospitalization within 3 months prior to step 1 registrationXx_NEWLINE_xXHistory of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXPatients who have had either myocardial infarction, coronary artery bypass graft, coronary artery stenting, hospital admission for heart related issues such as congestive heart failure or arrhythmia within the last 3 months, will not be allowed on protocolXx_NEWLINE_xXUnstable cardiovascular disease (eg, uncontrolled hypertension, peripheral vascular disease, congestive heart failure, cardiac arrhythmia, or acute coronary syndrome) within 6 months of starting study treatmentXx_NEWLINE_xXOther medical conditions including but not limited to:\r\n* History of liver disease such as cirrhosis, chronic active hepatitis, chronic persistent hepatitis or hepatitis B or C\r\n* Active infection requiring parenteral antibiotics\r\n* Immuno-compromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; NOTE: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial\r\n* New York Heart Association class II-IV congestive heart failure (serious cardiac arrhythmia requiring medication)\r\n* Myocardial infarction or unstable angina =< 6 months prior to registration\r\n* Congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias\r\n* Clinically significant peripheral vascular disease\r\n* History of central nervous system (CNS) disease (e.g., primary brain tumor, vascular abnormalities, etc.), clinically significant stroke or transient ischemic attack (TIA) =< 6 months prior to registration, seizures not controlled with standard medical therapy\r\n* History of hypertensive crisis or hypertensive encephalopathy\r\n* Therapeutic anticoagulation requiring international normalized ratio (INR) > 2.0Xx_NEWLINE_xXSerious intercurrent medical illness (e.g., symptomatic congestive heart failure)Xx_NEWLINE_xXHistory of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXSymptomatic congestive heart failure or radionuclide ventriculogram (RVG) or echocardiogram determined left ventricular ejection fraction of < 30%, active angina pectoris, or uncontrolled hypertensionXx_NEWLINE_xXPatients must not have serious intercurrent illness such as infection requiring intravenous (IV) antibiotics, or significant cardiac disease characterized by significant arrhythmia, unstable ischemic coronary disease or congestive heart failureXx_NEWLINE_xXSerious comorbidities (as determined by the investigator) such as, but not limited\n             to, active congestive heart failure or recent myocardial infarction. Patients who\n             require antifolate therapy for the management of comorbid conditions (e.g.,\n             rheumatoid arthritis) will be excluded from the trial.Xx_NEWLINE_xXWithin 30 days of registration: Absence of clinical decompensated congestive heart failure or uncontrolled arrhythmiaXx_NEWLINE_xXSymptomatic congestive heart failure (CHF)Xx_NEWLINE_xXUncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, uncontrolled peripheral vascular disease, myocardial infarction within preceding 12 months, cerebrovascular accident within preceding 12 months, pulmonary disease impairing functional status or requiring oxygen, impairment in gastrointestinal function that may affect or alter absorption of oral medications (such as malabsorption or history of gastrectomy or bowel resection)Xx_NEWLINE_xXSymptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 3 monthsXx_NEWLINE_xXAbsence of clinically significant cardiomyopathy, congestive heart failureXx_NEWLINE_xXCardiovascular disease problems including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke, or congestive heart failure within the last 6 monthsXx_NEWLINE_xXNo decompensated congestive heart failure (CHF), or uncontrolled arrhythmia; ejection fraction (EF) >= 35%Xx_NEWLINE_xXAbsence of clinically significant cardiomyopathy, congestive heart failureXx_NEWLINE_xXHas known symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmiaXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 monthsXx_NEWLINE_xXPatients with a history of cardiac disease including: (1) uncontrolled angina, congestive heart failure, or myocardial infarction within six months prior to study entry, (2) congenital long QT syndrome, (3) clinical significant ventricular arrhythmiasXx_NEWLINE_xXUnstable angina pectoris, symptomatic congestive heart failure, myocardial infarction\n             within 3 months of start of study treatment, serious uncontrolled cardiac arrhythmia\n             or any other clinically significant heart disease.Xx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:\r\n* Symptomatic congestive heart failure of New York heart Association class III or IV \r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia, left ventricular ejection fraction (LVEF) < 50% or any other clinically significant cardiac disease\r\n* Severely impaired lung function as defined as spirometry and diffusion capacity of the lung of carbon monoxide (DLCO) that is 50% of the normal predicted value and/or oxygen (02) saturation that is 88% or less at rest on room air\r\n* Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN (Note: optimal glycemic control should be achieved before starting trial therapy)\r\n* Active (acute or chronic) or uncontrolled severe infections\r\n* Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C)\r\n* Note: A detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients; hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and hepatitis C ribonucleic acid polymerase chain reaction (HCV RNA PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection; patients with positive results for HBV/HCV infection will be allowed in this study provided monitoring and prophylactic treatment are followedXx_NEWLINE_xXActive heart disease including myocardial infarction within previous 6 months, symptomatic coronary artery disease, uncontrolled arrhythmias, or symptomatic congestive heart failureXx_NEWLINE_xXSymptomatic uncontrolled coronary artery disease or congestive heart failureXx_NEWLINE_xXPatients who have a significant history of cardiac disease, i.e., uncontrolled hypertension, unstable angina, congestive heart failure, or uncontrolled arrhythmias within 6 months of registrationXx_NEWLINE_xXUncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, uncontrolled peripheral vascular disease, myocardial infarction within preceding 12 months, cerebrovascular accident within preceding 12 months, pulmonary disease impairing functional status or requiring oxygen, impairment in gastrointestinal function that may affect or alter absorption of oral medications (such as malabsorption or history of gastrectomy or bowel resection)Xx_NEWLINE_xXUncontrolled intercurrent illness considered by the investigator to constitute an unwarranted high risk for investigational drug treatment; examples include, but not limited to the following: \r\n* Uncontrolled serious infection; or \r\n* Unstable angina pectoris; or \r\n* Uncontrolled cardiac arrhythmia; or\r\n* Active second malignancy requiring treatment; or\r\n* Symptomatic congestive heart failureXx_NEWLINE_xXPatients with recent (? 6 months) cardiac angina, difficult to control congestive\n             heart failure, uncontrolled hypertension, or difficult to control cardiac arrhythmias\n             will be excludedXx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:\r\n* Symptomatic congestive heart failure of New York Heart Association class III or IV\r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease\r\n* Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C)\r\n** Note: a detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients; hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and hepatitis C virus (HCV) ribonucleic acid (RNA) polymerase chain reaction (PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infectionXx_NEWLINE_xXPrevious history of congestive heart failureXx_NEWLINE_xXPatients must be free of symptoms of uncontrolled cardiac disease including unstable angina, decompensated congestive heart failure, or arrhythmia; the ejection fraction by multi-gated acqusition scan (MUGA) must be > 45%Xx_NEWLINE_xXUncontrolled or significant heart disorder such as unstable anginaXx_NEWLINE_xXPatients must not have any grade III/IV cardiac disease as defined by the New York Heart Association Criteria (i.e., patients with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, and myocardial infarction within 6 months, or serious uncontrolled cardiac arrhythmia\r\n* Patients with a history of congestive heart failure (CHF) or at risk because of underlying cardiovascular disease or exposure to cardiotoxic drug should have an electrocardiogram (EKG) and echocardiogram performed to evaluate cardiac function as clinically indicated\r\n* Patients with evidence of congestive heart failure (CHF), myocardial infarction (MI), cardiomyopathy, or myositis should have a cardiac evaluation including lab tests and cardiology consultations as clinically indicated including EKG, creatine phosphokinase (CPK), troponin, and echocardiogramXx_NEWLINE_xXThe participant has symptomatic congestive heart failure or symptomatic cardiac arrhythmia.Xx_NEWLINE_xXSubjects with a history of class III or IV congestive heart failure or non-ischemic cardiomyopathy, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the previous 6 monthsXx_NEWLINE_xXSubjects with a known unstable or uncontrolled angina pectoris.Xx_NEWLINE_xXSubjects with known unstable or uncontrolled angina pectoris.Xx_NEWLINE_xXNo active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, uncontrolled thrombotic or hemorrhagic disorderXx_NEWLINE_xXhistory within the last 6 months of symptomatic congestive heart failure, myocardial infarction, or unstable anginaXx_NEWLINE_xXPatients with known unstable or uncontrolled angina pectorisXx_NEWLINE_xXCerebrovascular or cardiovascular event, or congestive heart failure within the last 6 months.Xx_NEWLINE_xXCLINICAL/LABORATORY CRITERIA: Patients must not have history of significant co-morbid illness inclusive of but not restricted to uncontrolled congestive cardiac failure, uncontrolled hypertension, history of myocardial infarction, unstable angina, coronary angioplasty, stenting or cerebrovascular accident within 6 months prior to registration or any other illness that in the assessment of the treating physician would compromise the ability of the patient to participate in this studyXx_NEWLINE_xXActive uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of ?2; including individuals who currently use digitalis, beta -blockers, or calcium channel blockers specifically for congestive heart failure), unstable angina, myocardial infarction within 12 months of enrollment, or ventricular arrhythmiaXx_NEWLINE_xXThe patient has clinically significant cardiovascular disease (e.g., uncontrolled or any NYHA Class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction or stroke within 6 months of study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).Xx_NEWLINE_xXClinically significant uncontrolled major cardiac, respiratory, renal, hepatic, gastrointestinal or hematologic disease but not limited to: \r\n* Symptomatic congestive heart failure, unstable angina, or cardiac dysrhythmia not controlled by pacer device\r\n* No myocardial infarction within 3 months of registrationXx_NEWLINE_xXActive congestive heart failure or ventricular arrhythmia requiring medicationXx_NEWLINE_xXHas a medical history of myocardial infarction, symptomatic congestive heart failure (CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmiaXx_NEWLINE_xXHas known symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmiaXx_NEWLINE_xXHas cardiovascular impairment, history of congestive heart failure greater than NYHA Class II uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months prior to the planned first dose of tazemetostat; or ventricular cardiac arrhythmia requiring medical treatmentXx_NEWLINE_xXUnstable angina pectorisXx_NEWLINE_xXHas evidence of active heart disease such as myocardial infarction within the 3 months prior to study entry; symptomatic coronary insufficiency congestive heart failure; moderate or severe pulmonary dysfunctionXx_NEWLINE_xXUnstable angina, symptomatic congestive heart failure or cardiac arrhythmia requiring anti-arrhythmic therapy (beta-blockers, calcium channel blockers and digoxin are allowed)Xx_NEWLINE_xXAbsence of history of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXMyocardial infarction, symptomatic congestive heart failure, unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 monthsXx_NEWLINE_xXHistory of myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure, within the 6 months prior to study drug administrationXx_NEWLINE_xXPatients must not have symptomatic congestive heart failure, coronary artery disease, cardiomyopathy, or uncontrolled arrhythmias; either an echocardiogram or multi-gated acquisition (MUGA) scan with an ejection fraction >= 45% must be obtained within 28 days prior to registration, or within 14 days prior to registration if the patient has received anthracycline in the 28 day window; (either method for measuring cardiac function is acceptable; however, the same scan must be used throughout treatment and follow-up to monitor the patient for cardiac toxicity); if the patient has symptoms suggestive of ischemia or congestive heart failure after that cardiac evaluation was done, a repeat study must be obtained prior to registrationXx_NEWLINE_xXUnstable medical conditions (eg, myocardial ischemia, active gastrointestinal bleed, severe congestive heart failure, anticipated need for major surgery within 6 months of randomization, coexisting chronic anemia unrelated to PNH)Xx_NEWLINE_xXHas cardiovascular impairment, history of congestive heart failure greater than NYHA Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months prior to the planned first dose of tazemetostat; or ventricular cardiac arrhythmia requiring medical treatmentXx_NEWLINE_xXUnstable angina and/or congestive heart failure requiring hospitalization within the last 6 monthsXx_NEWLINE_xXSignificant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension, and congestive heart failure related to primary cardiac disease, a history of a serious uncontrollable arrhythmia despite treatment, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the trial entry.Xx_NEWLINE_xXSignificant cardiovascular disease, including: Active clinically symptomatic left ventricular failure,uncontrolled hypertension, myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of study drug, history of serious ventricular arrhythmia, cardiac arrhythmias requiring anti-arrhythmic medications.Xx_NEWLINE_xXNo congestive heart failure < 6 monthsXx_NEWLINE_xXNo unstable angina pectoris < 6 monthsXx_NEWLINE_xXSerious medical illness, including any of the following: uncontrolled congestive heart failure, uncontrolled angina, myocardial infarction, cerebrovascular event within 6 months prior to the screening visitXx_NEWLINE_xXUncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failureXx_NEWLINE_xXUncontrolled heart diseaseXx_NEWLINE_xXUnstable angina.Xx_NEWLINE_xXPatients with clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemakerXx_NEWLINE_xXPatients with concurrent uncontrolled medical conditions that may interfere with their participation in the study or potentially affect the interpretation of the study data\r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia\r\n* Severely impaired lung function\r\n* Active (acute or chronic) or uncontrolled infection\r\n* Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy\r\n* Liver disease (i.e. cirrhosis, chronic active hepatitis, chronic persistent hepatitis)Xx_NEWLINE_xXActive cardiac disease defined as unstable angina, uncontrolled hypertension, myocardial infarction in the last six months (unless successfully treated with coronary artery bypass graft [CABG] or percutaneous transluminal coronary angioplasty [PTCA]), uncontrolled arrhythmia, or congestive heart failure; > 3 heart-related hospitalization in the past yearXx_NEWLINE_xXUncontrolled cardiac disease, such as uncontrolled hypertension, unstable angina, and/or congestive heart failure requiring hospitalization within the last 6 monthsXx_NEWLINE_xXOther clinically significant heart disease such as congestive heart failure requiring treatment or uncontrolled hypertension (blood pressure ? 160/95 mmHg).Xx_NEWLINE_xXHistory or presence of angina, myocardial infarction, clinically relevant valvular heart disease, uncontrolled hypertension, or congestive heart failure within the previous 12 months.Xx_NEWLINE_xXclinically significant heart disease including but not limited to: myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or known cardiac ejection fraction measurement of < 50 %;Xx_NEWLINE_xXUnstable medical conditions (eg, myocardial ischemia, active gastrointestinal bleed, severe congestive heart failure, anticipated need for major surgery within 6 months of randomization, coexisting chronic anemia unrelated to PNH).Xx_NEWLINE_xXSymptomatic cardiopulmonary disease (including congestive heart failure and hypertension), coronary artery disease, serious arrhythmia or chronic lung disease. Patients with these conditions who are stable with relatively minor symptoms and who are appropriate candidates for surgical treatment of their tumor need not be excludedXx_NEWLINE_xXClinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening.Xx_NEWLINE_xXSignificant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screeningXx_NEWLINE_xXEchocardiogram (ECHO) cardiogram and cardiology consultation required within 7 days prior to registration for patients with a history of congestive heart failure or cardiovascular disease or history of exposure to cardiotoxic agents who are not already excludedXx_NEWLINE_xXPatients with any other known disease (except carcinoma in-situ) or concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, cardiovascular disease including congestive heart failure, myocardial infarction within 6 months and uncontrolled hypertension, chronic renal disease [creatinine clearance < 20 ml/min using the Cockcroft and Gault formula], or active uncontrolled infection) which could compromise participation in the studyXx_NEWLINE_xXKnown active symptomatic congestive heart failureXx_NEWLINE_xXSevere or uncontrolled medical disease, including uncontrolled diabetes, congestive heart failure, chronic renal disease or chronic pulmonary diseaseXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 monthsXx_NEWLINE_xXA history of congestive heart failure, transmural myocardial infarction, symptomatic valvular disease, or high-risk arrhythmiaXx_NEWLINE_xXPatients with symptoms of congestive heart failure are not eligibleXx_NEWLINE_xXSubject has an ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, active bleeding or any other serious uncontrolled medical disorderXx_NEWLINE_xXPatient with unstable cardiac status including: 4.1. Unstable angina pectoris on medication 4.2. Documented myocardial infarction within 40 days prior to enrolment 4.3. Congestive heart failure NYHA class IV 4.4. Unstable arrhythmia status, already on anti-arrhythmic drugsXx_NEWLINE_xXPatients with active or history of cardiac (congestive heart failure [CHF], myocardial infarction, myocarditis) disease are excluded from this trialXx_NEWLINE_xXSignificant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, myocardial infarction within the last 6 months, uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.Xx_NEWLINE_xXCurrently active, clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, any Class 3 or 4 cardiac disease within 6 months of screeningXx_NEWLINE_xXActive uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of >= 2, including individuals who currently use digitalis specifically for congestive heart failure), unstable angina, myocardial infarction within 12 month of enrollment or ventricular arrhythmiaXx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions such as: a) unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease; b) symptomatic congestive heart failure of New York Heart Association class III or IV; c) active (acute or chronic) or uncontrolled severe infection (not responding to antibiotics), liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis (i.e. quantifiable hepatitis B virus-deoxyribonucleic acid [HBV-DNA] and/or positive hepatitis B surface antigen [HbsAg], quantifiable hepatitis C virus-ribonucleic acid [HCV-RNA]); d) known severely impaired lung function (spirometry and diffusing capacity of the lung for carbon monoxide [DLCO] 50% or less of normal and oxygen [O2] saturation 88% or less at rest on room air); e) active, bleeding diathesisXx_NEWLINE_xXSevere or uncontrolled hypertension, history of congestive heart failure, acute myocardial infarction, or severe coronary arterial diseaseXx_NEWLINE_xXSerious concomitant systemic disorders incompatible with the study (at the discretion of the investigator), such as significant cardiac or pulmonary morbidity (e.g. congestive heart failure, symptomatic coronary artery disease and/or cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months, or ongoing infection as manifested by feverXx_NEWLINE_xXMedically documented cardiac syncope, uncompensated congestive heart failure, myocardial infarction within the previous 6 months, unstable angina pectoris, clinically significant repetitive atrial or ventricular arrhythmias despite antiarrhythmic treatment, or severe orthostatic hypotension or clinically significant uncompensated autonomic insufficiencyXx_NEWLINE_xXUncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failureXx_NEWLINE_xXKnown congestive heart failure, significant ventricular arrhythmias, cirrhosis, grade 4/5 chronic kidney disease, uncontrolled diabetesXx_NEWLINE_xXActive coronary heart disease evidenced as angina or requiring medications to prevent anginaXx_NEWLINE_xXUncontrolled systemic disease including, but not limited to, ongoing or active systemic infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B or hepatitis CXx_NEWLINE_xXImpaired cardiac function including any of the following:\r\n* Myocardial infarction within 6 months of starting study drug;\r\n* A past medical history of clinically significant ECG abnormalities\r\n* Other clinically significant heart disease (e.g. uncontrolled congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an anti-hypertensive regimen)Xx_NEWLINE_xXHistory of congestive heart failure or other findings of ventricular dysfunctionXx_NEWLINE_xXSymptomatic congestive heart failureXx_NEWLINE_xXUnstable angina pectorisXx_NEWLINE_xXHas one of the following cardiac-related conditions: Congestive heart failure; angina pectoris; myocardial infarction (within 1 year of study start); uncontrolled hypertension; or uncontrolled arrhythmiasXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 monthsXx_NEWLINE_xXUncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, active peptic ulcer disease or gastritis, and active bleeding diathesesXx_NEWLINE_xXUncontrolled angina within 6 months before the Day 1 visit.Xx_NEWLINE_xXUncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failureXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months\r\n* Chronic hypertension on medical therapy does not constitute an exclusion criterionXx_NEWLINE_xXSignificant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of starting study drugXx_NEWLINE_xXThe participant has symptomatic congestive heart failure (CHF), left ventricular dysfunction (LVEF < 50%), severe myocardial insufficiency, cardiac arrhythmia, or cardiomyopathy.Xx_NEWLINE_xXSignificant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screeningXx_NEWLINE_xXSignificant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screeningXx_NEWLINE_xXKnown congestive heart failure requiring medical managementXx_NEWLINE_xXAny unstable, serious co-existing medical conditions including but not limited to myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure, or cerebrovascular accident within 6 months prior to screeningXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 monthsXx_NEWLINE_xXConcurrent severe and/or uncontrolled medical conditions which could compromise participation in the study such as unstable angina, myocardial infarction within 6 months, unstable symptomatic arrhythmia, uncontrolled diabetes, serious active or uncontrolled infectionXx_NEWLINE_xXUncontrolled intercurrent illness or serious medical conditions including, but not limited to:\r\n* Clinically significant, uncontrolled, major cardiac, respiratory, renal, hepatic, gastrointestinal, or hematologic disease\r\n* Active uncontrolled infection\r\n* Symptomatic congestive heart failure, unstable angina, or cardiac dysrhythmia not controlled by pacer device\r\n* No myocardial infarction within 3 months of registration\r\n* Symptomatic inflammatory bowel disease with uncontrolled diarrheaXx_NEWLINE_xXSignificant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screeningXx_NEWLINE_xXUncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure of New York Heart Association (NYHA) class III or IV, active coronary artery disease, unstable angina pectoris, cardiac arrhythmia, myocardia infraction =< 6 months prior to start of everolimus, uncontrolled hypertension (systolic pressure > 150 mmHg or diastolic pressure > 90 mmHg), uncontrolled seizure disorder, liver disease such as cirrhosis, decompensated liver disease, active and chronic hepatitis, known severely impaired lung function (spirometry and diffusing capacity of the lungs for carbon monoxide [DLCO] 50% or less of normal and oxygen [O2] saturation 88% or less at rest on room air), active bleeding diathesis, or psychiatric illness/social situations that would limit compliance with study requirementsXx_NEWLINE_xXAny other severe, uncontrolled medical condition, including uncontrolled diabetes mellitus or unstable congestive heart failure.Xx_NEWLINE_xXUncontrolled cardiac angina or symptomatic congestive heart failure (NYHA class III or IV)Xx_NEWLINE_xXUncontrolled angina within 3 months before C1D1.Xx_NEWLINE_xXAny significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol including:\r\n* History of myocardial infarction in the past year or unstable, severe cardiovascular disease including angina or congestive heart failure (CHF) with symptoms at rest, or clinically significant abnormalities on the electrocardiogram (ECG)\r\n* Clinically significant and/or unstable pulmonary, gastrointestinal, hepatic, or renal disease\r\n* Insulin-requiring diabetes or uncontrolled diabetes mellitus,\r\n* Uncontrolled hypertension (systolic blood pressure [BP] > 170 or diastolic blood pressure [BP] > 100)Xx_NEWLINE_xXCo-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens including but not limited to any of the following that would limit compliance with study requirements:\r\n* Ongoing or active severe infection\r\n* Liver disease such as cirrhosis\r\n* Decompensated liver disease\r\n* Symptomatic congestive heart failure (New York heart Association class III or IV)\r\n* Unstable angina pectoris, serious uncontrolled cardiac arrhythmia, myocardial infarction =< 6 months prior to registration\r\n* Known severely impaired lung function (spirometry and diffusing capacity of the lung for carbon monoxide [DLCO] 50% or less of normal and oxygen [O2] saturation 88% or less at rest on room air)\r\n* Active bleeding diathesis\r\n* Psychiatric illnessXx_NEWLINE_xXHistory of prior unstable angina, myocardial infarction, congestive heart failure (CHF), uncontrolled ventricular arrhythmias within 12 monthsXx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions such as:\r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease\r\n* Symptomatic congestive heart failure of New York heart Association class III or IV\r\n* Active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis or decompensated liver disease, and chronic hepatitis\r\n* Known severely impaired lung function (spirometry and diffusion capacity of carbon monoxide [DLCO] 50% or less of normal and oxygen [O2] saturation 88% or less at rest on room air)\r\n* Active, bleeding diathesisXx_NEWLINE_xXHistory of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXHistory of congestive heart failure or systolic dysfunction (LVEF <50%)Xx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.Xx_NEWLINE_xXHistory of symptomatic congestive heart failure within 6 months prior to the initiation of therapy on this protocolXx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions such as: a) unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction less than or equal to 6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease; b) symptomatic congestive heart failure of New York Heart Association class III or IV; c) active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable hepatitis B virus [HBV]-deoxyribonucleic acid [DNA] and/or positive hepatitis B surface antigen [HbsAg], quantifiable hepatitis C virus [HCV]-ribonucleic acid [RNA]); d) known severely impaired lung function (spirometry and diffusing capacity of the lung for carbon monoxide [DLCO] 50% or less of normal and oxygen [O2] saturation 88% or less at rest on room air); e) active, bleeding diathesisXx_NEWLINE_xXUnstable angina pectorisXx_NEWLINE_xXEvidence of uncontrolled illness such as symptomatic congestive heart failure, uncontrolled hypertension or unstable angina pectoris.Xx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 monthsXx_NEWLINE_xXHistory of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions such as:\r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease\r\n* Symptomatic congestive heart failure of New York Heart Association class III or IV\r\n* Active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable hepatitis B virus [HBV]-deoxyribonucleic acid [DNA] and/or positive hepatitis B virus surface antigen [HbsAg], quantifiable hepatitis C virus [HCV]-ribonucleic acid [RNA])\r\n* Known severely impaired lung function (spirometry and diffusing capacity of the lung for carbon monoxide [DLCO] 50% or less of normal and oxygen [O2] saturation 88% or less at rest on room air)\r\n* Active, bleeding diathesisXx_NEWLINE_xXCongestive heart failure (CHF) within 6 months prior to first doseXx_NEWLINE_xXEvidence of uncontrolled illness such as symptomatic congestive heart failure, uncontrolled hypertension or unstable angina pectoris.Xx_NEWLINE_xXSubjects with known unstable or uncontrolled angina pectoris.Xx_NEWLINE_xXUncontrolled angina within 6 monthsXx_NEWLINE_xXEvidence of uncontrolled congestive heart failureXx_NEWLINE_xXUnstable anginaXx_NEWLINE_xXPatients with evidence of uncontrolled current myocardial impairment (e.g. unstable ischemic heart disease, uncontrolled arrhythmia, symptomatic valvular dysfunction not controlled on medical therapy, uncontrolled hypertensive heart disease, and uncontrolled congestive heart failure)Xx_NEWLINE_xXSymptomatic congestive heart failureXx_NEWLINE_xXHistory of congestive heart failure (CHF)Xx_NEWLINE_xXAny of the following cardiac conditions: Documented congestive heart failure; Myocardial infarction within 6 months prior to study entry; Unstable angina within 6 months prior to study entry; Symptomatic arrhythmiaXx_NEWLINE_xXUncontrolled inter-current illness including, but not limited to ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, or serious, uncontrolled cardiac arrhythmia, that might jeopardize the ability of the patient to receive the therapy program outlined in this protocol with reasonable safetyXx_NEWLINE_xXHistory of myocardial infarction =< 180 days (6 months), or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXPatients with unstable angina or serious arrhythmiaXx_NEWLINE_xXHas symptomatic congestive heart failure (CHF)Xx_NEWLINE_xXClinically significant cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months prior to study entry; unstable angina, congestive heart failure or a serious cardiac arrhythmia requiring medication.Xx_NEWLINE_xXHistory of myocardial infarction =< 180 days prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXActive heart disease including myocardial infarction within previous 6 months, symptomatic coronary artery disease, arrhythmias not controlled with medication, or symptomatic congestive heart failureXx_NEWLINE_xXSubjects with known unstable or uncontrolled angina pectoris.Xx_NEWLINE_xXHistory of congestive heart failure or myocardial infarction within the previous six monthsXx_NEWLINE_xXSymptomatic congestive heart failure or unstable angina pectorisXx_NEWLINE_xXActive cardiac disease\r\n* Any prior myocardial infarction (asymptomatic changes on electrocardiogram [EKG] suggestive of old myocardial infarction [MI] is not an exclusion)\r\n* Documented congestive heart failure (CHF)\r\n* Current use of any therapy specifically for CHF\r\n* Current uncontrolled hypertension (diastolic > 100 mmHg or systolic > 200 mmHg)\r\n* Clinically significant pericardial effusionXx_NEWLINE_xXRecent (=< 6 months) myocardial infarction, unstable angina, difficult-to-control congestive heart failure, uncontrolled hypertension on appropriate therapy, or difficult to control cardiac arrhythmiasXx_NEWLINE_xXActive heart disease including but not limited to symptomatic congestive heart failure, symptomatic coronary artery disease, symptomatic angina pectoris, symptomatic myocardial infarction, or symptomatic congestive heart failure; also patients with a history of myocardial infarction that is < 1 year prior to registration, or patients with previous congestive heart failure (< 1 year prior to registration) requiring pharmacologic support or with left ventricular ejection fraction < 45%Xx_NEWLINE_xXSignificant or uncontrolled congestive heart failure (CHF), myocardial infarction or significant ventricular arrhythmias within the last six months.Xx_NEWLINE_xXActive heart disease including but not limited to symptomatic congestive heart failure, symptomatic coronary artery disease, symptomatic angina pectoris, symptomatic myocardial infarction, or symptomatic congestive heart failureXx_NEWLINE_xXSubjects with uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure, myocardial infarction within the past 6 months or serious uncontrolled cardiac arrhythmia are not eligibleXx_NEWLINE_xXSerious concomitant systemic disorders incompatible with the study (at the discretion of the investigator), such as significant cardiac or pulmonary morbidity e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months, ongoing infection as manifested by feverXx_NEWLINE_xXMyocardial infarction having occurred less than 6 months before inclusion, any known uncontrolled arrhythmia, symptomatic angina pectoris, active ischemia, or cardiac failure not controlled by medicationsXx_NEWLINE_xXClinically significant cardiac disease within 12 months of study enrollment, including myocardial infarction, unstable angina, congestive heart failure, or ongoing arrhythmias requiring medication or pacemakerXx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: symptomatic congestive heart failure of New York Heart Association class III or IV; unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease; severely impaired lung function as defined as spirometry and diffusing capacity of the lungs for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or oxygen (O2) saturation that is 88% or less at rest on room air; active (acute or chronic) or uncontrolled severe infections; liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C); note: a detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients; hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and hepatitis C virus (HCV) ribonucleic acid (RNA) polymerase chain reaction (PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection; a known history of human immunodeficiency virus (HIV) seropositivity; impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection); patients with an active, bleeding diathesisXx_NEWLINE_xXSignificant or uncontrolled congestive heart failure (CHF), myocardial infarction, significant ventricular arrhythmias within the last six months or significant pulmonary dysfunction.Xx_NEWLINE_xXAny serious medical condition including but not limited to, uncontrolled hypertension, uncontrolled congestive heart failure, uncontrolled diabetes mellitus, active/symptomatic coronary artery disease, chronic obstructive pulmonary disease (COPD), left ventricular ejection fraction (LVEF) less than 40, renal failure, active infection, active hemorrhage, laboratory abnormality, or psychiatric illness that, in the investigators opinion places the patient at unacceptable risk and would prevent the subject from signing the informed consent form; patients with history of cardiac arrhythmias should have cardiac evaluation and clearanceXx_NEWLINE_xXThe patient has a history of uncontrolled angina, arrhythmias, or congestive heart failureXx_NEWLINE_xXSevere illness or organ dysfunction involving the heart, kidney, liver or other organ system (e.g. active infection, clinically relevant impairment of cardiac function, severe heart failure/cardiac insufficiency, unstable angina pectoris or history of recent myocardial infarction), which in the opinion of the investigator precludes treatment with LDAC.Xx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 monthsXx_NEWLINE_xXOther clinically significant heart disease (e.g. uncontrolled congestive heart failure or uncontrolled hypertension)Xx_NEWLINE_xXHistory of acute myocardial infarction within prior 3 months, uncontrolled angina, uncontrolled arrhythmia, or uncontrolled congestive heart failureXx_NEWLINE_xXPatients must not have unstable angina or NYHA classification of congestive heart failure of grade >= 2Xx_NEWLINE_xXPatients with clinically significant illnesses which could compromise participation in the study, including, but not limited to: active or uncontrolled infection; or unstable angina pectoris, myocardial infarction within the past 6 months, or uncontrolled cardiac arrhythmiaXx_NEWLINE_xXNo decompensated congestive heart failure (CHF), or uncontrolled arrhythmiaXx_NEWLINE_xXPatients with evidence of severe or uncontrolled systemic disease, or any concurrent condition, which could compromise participation in the study, including, but not limited to, active or uncontrolled infection, immune deficiencies, uncontrolled hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection unless sustained virologic response to HCV therapy, uncontrolled diabetes, serious non-healing ulcer, wound or bone fracture, history of intra-abdominal abscess, abdominal fistula or gastrointestinal perforation within 28 days of treatment, history of pulmonary embolism in the past 12 months, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry, class III or IV heart failure as defined by the NYHA functional classification system, stroke/cerebrovascular accident or transient ischemic attack within the past 12 months or psychiatric illness/social situations which would jeopardize compliance with the protocolXx_NEWLINE_xXSevere, concurrent illness including congestive heart failure, significant cardiac disease and uncontrolled hypertension, that would likely prevent the patient from being able to comply with the study protocolXx_NEWLINE_xXSerious concomitant systemic disorders incompatible with the study (at the discretion of the investigator), such as significant cardiac or pulmonary morbidity e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months, ongoing infection as manifested by feverXx_NEWLINE_xXHistory of significant cardiovascular, neurological, endocrine, gastrointestinal, respiratory, or inflammatory illness that could preclude study participation, pose an undue medical hazard, or interfere with the interpretation of the study results, including but not limited to congestive heart failure (NYHA Class 3 or 4), unstable angina; cardiac arrhythmia, recent (within past 6 months) myocardial infarction or stroke; uncontrolled hypertension; diabetes mellitus with >2 episodes of ketoacidosis in the preceding 12 months, COPD requiring >2 hospitalizations in preceding 12 monthsXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within 6 months before randomization in the study.Xx_NEWLINE_xXPatients with known overt cardiac disease, including but not limited to a history of myocardial infarction, severe or unstable angina, clinically significant peripheral vascular disease, grade 2 or greater heart failure, or serious and inadequately controlled cardiac arrhythmia are not eligibleXx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:\r\n* Symptomatic congestive heart failure of New York heart Association Class III or IV\r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease\r\n* Severely impaired lung function as defined as spirometry and diffusion capacity of carbon monoxide (DLCO) that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air\r\n* Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN\r\n* Active (acute or chronic) or uncontrolled severe infections\r\n* Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C)\r\n* Note: A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients; hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and hepatitis C virus (HCV) ribonucleic acid (RNA) polymerase chain reaction (PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infectionXx_NEWLINE_xXCardiovascular disease problems including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke, or congestive heart failure within the last 6 monthsXx_NEWLINE_xXUncompensated congestive heart failureXx_NEWLINE_xXSerious concomitant systemic disorders incompatible with the study (at the discretion of the investigator), such as significant cardiac or pulmonary morbidity e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months, ongoing infection as manifested by feverXx_NEWLINE_xXUnstable anginaXx_NEWLINE_xXPresence of uncontrolled hypertension or congestive heart failure, or acute myocardial infarction within 6 months of entryXx_NEWLINE_xXUnstable anginaXx_NEWLINE_xXNon-controlled intercurrent diseases, including active infections, symptomatic congestive heart failure, unstable chest angina or heart arrhythmia, as well as mentally incapable patientsXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months; Note: prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevantXx_NEWLINE_xXOther clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension)Xx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:\r\n* Unstable angina pectoris (at any time), symptomatic congestive heart failure (New York Heart Association [NYHA] III, IV) (at any time), serious uncontrolled cardiac arrhythmia (at any time), myocardial infarction, cerebrovascular accidents, or symptomatic left ventricular dysfunction =< 6 months prior to first study treatment\r\n* Active bleeding diathesis\r\n* Known severely impaired lung function defined as spirometry and diffusion capacity of the lung for carbon monoxide (DLCO) =< 50% of normal oxygen saturation at rest =< 88% on room air\r\n* Symptomatic intrinsic lung disease requiring oxygen supplementation at baseline\r\n* Uncontrolled diabetes mellitus as defined by glycosylated hemoglobin (HbA1c) > 8% despite adequate therapy; patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary\r\n* Any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study\r\n* Liver disease such as cirrhosis or decompensated liver disease, or active and chronic hepatitis (i.e. quantifiable hepatitis B virus [HBV]-deoxyribonucleic acid [DNA] and/or positive hepatitis B surface antigen [HBsAg], quantifiable hepatitis C virus [HCV]-ribonucleic acid [RNA])Xx_NEWLINE_xXHistory of acute myocardial infarction, unstable angina, congestive heart failure, or arrhythmia within the last three monthsXx_NEWLINE_xXGrade 2 or greater congestive heart failureXx_NEWLINE_xXGrade >= 2 heart failure or history of unstable anginaXx_NEWLINE_xXSymptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 3 monthsXx_NEWLINE_xXClinically significant cardiac disease (including symptomatic congestive heart failure, myocardial infarction, unstable angina pectoris, or serious, uncontrolled cardiac arrhythmia) within 1 year of study enrollmentXx_NEWLINE_xXPatients with clinically significant illnesses which could compromise participation in the study, including, but not limited to, uncontrolled infection, uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia, stroke/cerebrovascular accident within the past 6 months, or psychiatric illness/social situations that in the investigator’s opinion would make it undesirable for the patient to participate in the trial, or which would jeopardize compliance with the protocolXx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions such as: \r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease\r\n* Symptomatic congestive heart failure of New York Heart Association class III or IV\r\n* Active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable hepatitis B virus [HBV]-DNA and/or positive hepatitis B surface antigen [HbsAg], quantifiable hepatitis C virus [HCV]-ribonucleic acid [RNA])\r\n* Known severely impaired lung function (e.g. spirometry and diffusing capacity of the lung for carbon monoxide [DLCO] 50% or less of normal and oxygen [O2] saturation 88% or less at rest on room air)\r\n* Active, bleeding diathesisXx_NEWLINE_xXEXPANSION COHORT ONLY: Any serious and/or unstable pre-existing medical, psychiatric, or other condition (including lab abnormalities) that could interfere with subject safety, obtaining informed consent or compliance to study procedures\r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ?6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, ventricular arrhythmias, active ischemic heart disease, or any other clinically significant cardiac disease\r\n* Symptomatic congestive heart failure of New York heart Association Class III or IV\r\n* Active (acute or chronic) or uncontrolled severe infection \r\n* Liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable HBV-DNA and/or positive HbsAg, quantifiable HCV-RNA)\r\n* Known severely impaired lung function (e.g. spirometry and DLCO 50% or less of normal and O2 saturation 88% or less at rest on room air)active, bleeding diathesis \r\n* Severe or uncontrolled infection, severe malnutrition\r\n* Chronic renal disease\r\n* Active upper GI tract ulcerationXx_NEWLINE_xXUnstable anginaXx_NEWLINE_xXUnstable angina pectoris ?6 months prior to study participationXx_NEWLINE_xXThe subject has uncontrolled significant intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled congestive heart failure, unstable angina pectoris within 6 months, stroke within 6 months, myocardial infarction within 6 months, or uncontrolled cardiac arrhythmias, uncontrolled hypertensionXx_NEWLINE_xXUncontrolled intercurrent illness (including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any patient known to have evidence of acute or chronic hepatitis B, hepatitis C or HIV)Xx_NEWLINE_xXUnstable anginaXx_NEWLINE_xXPatients must not have significant cardiac disease characterized by symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmiaXx_NEWLINE_xXPatients must not have serious intercurrent illness such as infection requiring IV antibiotics, or significant cardiac disease characterized by significant arrhythmia, ischemic coronary disease or congestive heart failureXx_NEWLINE_xXPatients must not have serious intercurrent illness such as infection requiring IV antibiotics, or significant cardiac disease characterized by significant arrhythmia, ischemic coronary disease or congestive heart failureXx_NEWLINE_xXHistory of hospitalization for Congestive Heart FailureXx_NEWLINE_xXIf the patient requires surgery of the bone metastasis, clinically serious comorbidities that render patient not medically fit for surgery (e.g. congestive heart failure, symptomatic coronary artery disease, cardiac arrhythmias and chronic lung disease not well controlled with medication; myocardial infarction within 12 months of enrollment)Xx_NEWLINE_xXHistory of heart diseaseXx_NEWLINE_xXUncontrolled angina, congestive heart failure or myocardial infarction (MI) within (6 months)Xx_NEWLINE_xXHistory of heart disease.Xx_NEWLINE_xXAny other concurrent severe known disease (except carcinoma in-situ) concurrent severe and/or uncontrolled medical condition including congestive heart failure grade III or IV according to the NYHA classification or with ejection fraction < 50%, etc.Xx_NEWLINE_xXPatients with the clinical diagnosis of congestive heart failure or angina pectoris are NOT eligibleXx_NEWLINE_xXSevere cardiovascular disease, i.e., arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart diseaseXx_NEWLINE_xXActive, uncontrolled infection or severe concurrent medical disease, including but not limited to congestive heart failure, cardiac arrhythmias, or psychiatric illnessXx_NEWLINE_xXCardiovascular disease problems including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke, or congestive heart failure within the last 6 monthsXx_NEWLINE_xXPatients cannot have known cardiac disease (either arrhythmia or congestive heart failure) requiring treatmentXx_NEWLINE_xXHave one of the following cardiac-related conditions: Congestive heart failure or angina pectoris (except if medically controlled); myocardial infarction (within 1 year of study start); uncontrolled hypertension; or uncontrolled arrhythmiasXx_NEWLINE_xXPatients with congestive heart failure with ejection fraction (EF) < 45% or uncontrolled cardiac disease (such as uncontrolled cardiac arrhythmia, uncontrolled coronary artery disease [CAD] with active symptoms due to CAD defined as unstable angina) are excluded from initiation of study treatmentXx_NEWLINE_xXSignificant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screeningXx_NEWLINE_xXMyocardial infarction in the previous 12 weeks. Active ischemia or any other uncontrolled cardiac condition such as angina pectoris, significant cardiac arrhythmia requiring therapy, uncontrolled hypertension, or CHF.Xx_NEWLINE_xXClinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) =< 6 months prior to enrollmentXx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions such as: \r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease\r\n* Symptomatic congestive heart failure of New York Heart Association class III or IV\r\n* Known severely impaired lung function (spirometry and diffusing capacity of the lung for carbon monoxide [DLCO] 50% or less of normal and oxygen [O2] saturation 88% or less at rest on room air)\r\n* Active, bleeding diathesisXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 monthsXx_NEWLINE_xXSignificant or uncontrolled congestive heart failure (CHF), myocardial infarction or significant ventricular arrhythmias within the last six months.Xx_NEWLINE_xXCardiac function: \r\n* ARM A: No evidence of uncontrolled heart failure or active angina\r\n* ARM B: No limitationXx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions such as:\r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease\r\n* Symptomatic congestive heart failure of New York Heart Association class III or IV\r\n* Active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis (i.e quantifiable hepatitis B virus [HBV]-DNA and/or positive hepatitis surface antigen [HbsAg], quantifiable hepatitis C virus[HCV]-ribonucleic acid [RNA])\r\n* Known severely impaired lung function (spirometry and diffusing capacity of the lungs for carbon monoxide [DLCO] 50% or less of normal and oxygen [O2] saturation 88% or less at rest on room air)\r\n* Active, bleeding diathesisXx_NEWLINE_xXClinically significant history of cardiovascular disease (history of unstable angina, congestive heart failure, uncontrolled hypertension, myocardial infarction or valvular heart disease)Xx_NEWLINE_xXClinically significant and/or uncontrolled heart disease such as congestive heart failure (CHF) requiring treatment (NYH grade ?2), hypertension or arrhythmiaXx_NEWLINE_xXActive heart disease including but not limited to symptomatic congestive heart failure, symptomatic coronary artery disease, symptomatic angina pectoris, symptomatic myocardial infarction or symptomatic congestive heart failureXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 monthsXx_NEWLINE_xXEvidence of active heart disease within the 3 months prior to study entry; symptomatic coronary insufficiency or heart block; congestive heart failure; moderate or severe pulmonary dysfunction, torsades de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia, heart block, or congenital long QT syndromeXx_NEWLINE_xXMyocardial infarction within 1 year before enrollment, symptomatic congestive heart failure, unstable angina, or unstable cardiac arrhythmia requiring medicationXx_NEWLINE_xXUnstable anginaXx_NEWLINE_xXPatients with clinically significant cardiac disease not well controlled with medication (e.g., congestive heart failure, symptomatic coronary artery disease e.g. angina, and cardiac arrhythmias) or myocardial infarction within the last 12 monthsXx_NEWLINE_xXCardiovascular disease, including recent history or currently clinically symptomatic and uncontrolled: congestive heart failure, arrhythmia, angina, QTc prolongation or other QTc risk factors, myocardial infarctionXx_NEWLINE_xXSerious intercurrent medical illness (e.g., symptomatic congestive heart failure)Xx_NEWLINE_xXHave other severe concurrent disease or serious organ dysfunction involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo treatment including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 monthsXx_NEWLINE_xXPatients with unstable cardiac status including:\r\n* Unstable angina pectoris on medication\r\n* Patients with documented myocardial infarction within six months of protocol entry\r\n* Congestive heart failure requiring medication (other than diuretic)\r\n* Patients on anti-arrhythmic drugsXx_NEWLINE_xXSerious medical illness including but not limited to uncontrolled congestive heart failure, uncontrolled angina, myocardial infarction or cerebrovascular event with 6 months of registration, history of chronic active hepatitis or history of human immunodeficiency virus (HIV) or an active bacterial infection will not be eligibleXx_NEWLINE_xXSymptomatic and/or serious uncontrolled arrhythmiaXx_NEWLINE_xXHistory of myocardial infarction =< 168 days (6 months), or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXPatient has had clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) =< 1 year before randomizationXx_NEWLINE_xXPatients with serious medical illnesses, including any of the following: uncontrolled congestive heart failure, uncontrolled angina, myocardial infarction, cerebrovascular event within six months prior to study entryXx_NEWLINE_xXPatients must not have clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) =< 1 year before randomizationXx_NEWLINE_xXPatients with congestive heart failure or significant arrhythmiaXx_NEWLINE_xXHistory of documented congestive heart failure, angina pectoris requiring medication, electrocardiogram (ECG) evidence of transmural myocardial infraction, poorly controlled hypertension, clinically significant valvular heart disease, or high-risk uncontrollable arrhythmiasXx_NEWLINE_xXKnown systolic or diastolic dysfunction or heart failureXx_NEWLINE_xXNo clinically significant history of cardiac disease, (i.e. uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the past year, or cardiac ventricular arrhythmias requiring medication)Xx_NEWLINE_xXUnstable anginaXx_NEWLINE_xXPatients with a history of unstable or newly diagnosed angina pectoris, documented history of current serious arrhythmia or congestive heart failure (CHF) or recent myocardial infarction (within 6 months of enrollment)Xx_NEWLINE_xXHas had within the past 6 months the occurrence or persistence of one or more of the following medical conditions that could not be controlled with usual medical care (e.g., required emergency care or hospitalization): hypertension, angina, congestive heart failure, diabetes, seizure disorder.Xx_NEWLINE_xXSevere concomitant illness i.e. chronic obstructive pulmonary disease (COPD), ischemic heart disease (IHD), active congestive cardiac failure (CCF), active angina pectoris, uncontrolled arrhythmia, uncontrolled hypertensionXx_NEWLINE_xXHas a medical history of symptomatic Congestive Heart Failure (CHF) (NYHA classes II-IV) or serious cardiac arrhythmia.Xx_NEWLINE_xXUncontrolled intercurrent illnesses including, but not limited to symptomatic congestive heart failure, severe oxygen dependent chronic obstructive pulmonary disease, unstable angina or uncontrolled cardiac arrhythmia that could jeopardize the subject’s ability to receive the chemotherapy described in the protocol safelyXx_NEWLINE_xXPatients with uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure, history of myocardial infarction within the previous six months, or serious uncontrolled cardiac arrhythmia.Xx_NEWLINE_xXSymptomatic congestive heart failureXx_NEWLINE_xXUnstable angina pectorisXx_NEWLINE_xXHeart failure or significant heart disease including significant arrhythmias, myocardial infarction within the last 3 months, unstable angina, documented ejection fraction < 30%, or current digoxin therapyXx_NEWLINE_xXPatients with history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with an ejection fraction under 40%.Xx_NEWLINE_xXUncontrolled arrhythmia or heart failureXx_NEWLINE_xXUnstable angina pectoris.Xx_NEWLINE_xXHistory of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXCongestive heart failure.Xx_NEWLINE_xXHistory of symptomatic congestive heart failure or serious cardiac arrhythmia requiring treatmentXx_NEWLINE_xXHistory of congestive heart failure;Xx_NEWLINE_xXSerious concomitant systemic disorders incompatible with the study (at the discretion of the investigator), such as significant cardiac or pulmonary morbidity e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months, ongoing infection as manifested by feverXx_NEWLINE_xXPatients with history of congestive heart failureXx_NEWLINE_xXActive, uncontrolled infection or severe concurrent medical disease, including but not limited to congestive heart failure, cardiac arrhythmias, or psychiatric illnessXx_NEWLINE_xXCardiovascular disease including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke, or congestive heart failure within the last 6 monthsXx_NEWLINE_xXSymptomatic congestive heart failureXx_NEWLINE_xXSevere, concurrent illness including congestive heart failure, significant cardiac disease and uncontrolled hypertension, that would likely prevent the patient from being able to comply with the study protocolXx_NEWLINE_xXUncontrolled or symptomatic anginaXx_NEWLINE_xXHistory of congestive heart failure (CHF)Xx_NEWLINE_xXNo evidence of congestive heart failure, symptoms of coronary artery disease, myocardial infarction less than 6 months prior to entry, serious cardiac arrhythmias, or unstable anginaXx_NEWLINE_xXLife threatening illness (e.g., congestive heart failure, uncontrolled angina or myocardial infarction in the prior six months)Xx_NEWLINE_xXAny severe acute or chronic medical condition including uncontrolled diabetes mellitus, severe renal impairment, history of cardiovascular disease (uncontrolled hypertension, arterial thrombotic events in the past 6 months, congestive heart failure, severe or unstable angina pectoris, recent myocardial infraction within last 6 months or uncontrolled cardiac arrhythmia), which could impair the ability of the patient to participate to the study or interfere with interpretation of study results, or patient unable to comply with the study procedures.Xx_NEWLINE_xXPatients with severe cardiac disease including symptomatic congestive heart failure, unstable angina, or have experience an acute myocardial infarction within the past 6 months; please note: patients with chronic obstructive pulmonary disease (COPD) are not excludedXx_NEWLINE_xXActive symptomatic congestive heart failureXx_NEWLINE_xXKnown unstable or uncontrolled angina pectorisXx_NEWLINE_xXCardiopulmonary function criteria:\r\n* Current unstable arrhythmia requiring treatment\r\n* History of symptomatic congestive heart failure\r\n* History of myocardial infarction within 6 months of enrollment\r\n* Current unstable angina\r\n* Family history of long QT syndromeXx_NEWLINE_xXMust not have a serious cardiac condition, such as congestive heart failure, unstable angina pectoris, or heart attack within the last 3 months.Xx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.Xx_NEWLINE_xXHistory of uncontrolled cardiac disease (e.g., uncontrolled hypertension, unstable angina, myocardial infarction within prior 6 months, untreated known coronary artery disease, uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fractionXx_NEWLINE_xXPatients with preexisting cardiac conditions, including uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure will not be eligibleXx_NEWLINE_xXEvidence of poor cardiovascular function defined as b-type natriuretic peptide (BNP) > 100 pg/mL, or history of congestive heart failure, unstable angina, uncontrolled hypertension, or clinically significant ventricular arrhythmias at screening;Xx_NEWLINE_xXHistory of or current cardiovascular risk including myocardial infarction, ? Class II congestive heart failure, uncontrolled arrhythmias, or refractory hypertensionXx_NEWLINE_xXThe patient has had congestive heart failure, unstable angina, a myocardial infarction, cardiac conduction abnormality or pacemaker or a stroke within 3 months of entering the study.Xx_NEWLINE_xXSerious illnesses, such as: cardiovascular disease (uncontrolled congestive heart failure, uncontrolled hypertension, cardiac ischemia, myocardial infarction, and severe cardiac arrhythmia), bleeding disorders, symptomatic autoimmune diseases, severe obstructive or restrictive pulmonary diseases, uncontrolled endocrine disorders (hypothyroidism, hyperthyroidism and diabetes mellitus), retinopathy, active systemic infections, and inflammatory bowel disorders; this includes known human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS)-related illness, or active hepatitis B virus (HBV) and hepatitis C virus (HCV)Xx_NEWLINE_xXCongestive heart failure (CHF) currently requiring therapyXx_NEWLINE_xXClinically significant cardiac disease not well controlled with medication (e.g., congestive heart failure, symptomatic coronary artery disease e.g. angina, and cardiac arrhythmias) or myocardial infarction within the last 12 months.Xx_NEWLINE_xXAny severe concurrent disease or condition (including active, uncontrolled systemic infection, symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia) that, in the judgment of the Investigator, would make the patient inappropriate for study participationXx_NEWLINE_xXThe subject has uncontrolled significant intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled congestive heart failure, unstable angina pectoris within 6 months, stroke within 6 months, myocardial infarction within 6 months, or uncontrolled cardiac arrhythmias, uncontrolled hypertensionXx_NEWLINE_xXActive congestive heart failure or ventricular arrhythmiaXx_NEWLINE_xXSymptomatic congestive heart failure;Xx_NEWLINE_xXCongestive heart failure or uncontrolled angina pectoris, previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension, or dysrhythmias.Xx_NEWLINE_xXPART I: Co-morbid condition that would affect survival: end stage congestive heart failure, unstable angina, myocardial infarction within 6 weeks of study, uncontrolled blood sugars >= 300 mg/dL, participants with known chronic active hepatitis or cirrhosisXx_NEWLINE_xXPART II: Co-morbid condition that would affect survival: end stage congestive heart failure, unstable angina, myocardial infarction within 6 weeks of study, uncontrolled blood sugars >= 300mg/dL, participants with known chronic active hepatitis or cirrhosisXx_NEWLINE_xXCongestive heart failure (CHF) currently requiring therapyXx_NEWLINE_xXUnstable angina pectorisXx_NEWLINE_xXConcurrent severe and/or uncontrolled medical conditions which could compromise participation in the study such as unstable angina, myocardial infarction within 6 months, unstable symptomatic arrhythmia, uncontrolled diabetes, serious active or uncontrolled infectionXx_NEWLINE_xXConcurrent severe or uncontrolled medical disease (including but not limited to history of ventricular arrhythmia or symptomatic conduction abnormality within 12 months, ongoing or active systemic infection, diabetes, hypertension, coronary artery disease, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations) that, in the opinion of the Investigator, would compromise the safety of the patient or compromise the ability of the patient to complete the study.Xx_NEWLINE_xXHas an active infection, congestive heart failure, slow heart rate, or other uncontrolled disease other than cancerXx_NEWLINE_xXSignificant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension, congestive heart failure related to primary cardiac disease, any condition requiring anti-arrhythmic therapy, ischemic or valvular heart disease, or a myocardial infarction within the past 6 monthsXx_NEWLINE_xXActive heart diseaseXx_NEWLINE_xXUncontrolled angina within 3 months of Screening visit;Xx_NEWLINE_xXUnstable congestive heart failureXx_NEWLINE_xXPatient has a major medical or co-morbid condition(s) that the investigator believes might compromise safe participation in the study (such as uncontrolled lung, kidney, or liver problems; uncontrolled infection; a history of congestive heart failure; or an electrocardiogram suggesting significant problems with the heart).Xx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: \r\n* Symptomatic congestive heart failure of New York Heart Association class III or IV\r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease\r\n* Concomitant use of drugs with a risk of causing torsades de pointes\r\n* Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN; note: optimal glycemic control should be achieved before starting trial therapy\r\n* Active (acute or chronic) or uncontrolled severe infections\r\n* Liver disease such as cirrhosis; note: a detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients; hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and hepatitis C virus (HCV) ribonucleic acid (RNA) polymerase chain reaction (PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infectionXx_NEWLINE_xXImpaired cardiac function or clinically significant heart disease, including any one of the following: congestive heart failure, angina pectoris within 3 months, acute myocardial infarction within 3 months, Fridericia corrected QT interval (QTcF) > 450 milliseconds (msec) for males and > 470 msec for females on the screening electrocardiogram (ECG), history of clinically significant ECG abnormalities, family history of prolonged QT-interval syndrome, or 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_xXCardiovascular events, such as myocardial infarction, unstable/severe angina, coronary/peripheral artery bypass graft, unstable cardiac arrhythmia requiring medication, congestive heart failure (NYHA > class II), within 2 yearsXx_NEWLINE_xXHistory of heart failure or serious cardiac arrhythmiaXx_NEWLINE_xXClinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to first study treatment, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities.*Xx_NEWLINE_xXHistory of active current coronary artery disease or unstable anginaXx_NEWLINE_xXPatients must not have serious intercurrent illness such as infection requiring IV antibiotics, or significant cardiac disease characterized by significant arrhythmia, uncontrolled hypertension, unstable ischemic coronary disease or congestive heart failureXx_NEWLINE_xXActive heart disease including myocardial infarction (MI) within previous 3 months, symptomatic coronary artery disease (CAD), arrhythmias not controlled by medication, or uncontrolled CHFXx_NEWLINE_xXSubjects with any one of the following: 1) Congestive heart failure, 2) Myocardial infarction within 12 months prior to starting study treatment, 3) Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectorisXx_NEWLINE_xXClinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months of study entry, uncontrolled congestive heart failure, and uncontrolled arrhythmia. Subjects with congestive heart disease or arrhythmia such as atrial fibrillation whose cardiac disease is well controlled on a stable medical regimen are eligible.Xx_NEWLINE_xXEvidence of severe or uncontrolled systemic disease or any concurrent condition – including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, unstable hypertension, seizure disorder, or psychiatric illness – which in the Investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocolXx_NEWLINE_xXClinically significant cardiac disease as judged by the investigator including unstable angina, acute myocardial infarction within 6 months prior to randomization, uncontrolled congestive heart failure, and uncontrolled arrhythmia. Subjects with congestive heart disease or arrhythmias such as atrial fibrillation whose cardiac disease is well controlled on a stable medical regimen are eligible.Xx_NEWLINE_xXc. Significant cardiovascular dysfunction within the past 6 months including symptomatic cardiac ischemia, arrhythmia or congestive heart failure requiring hospitalization or emergency room visit within last 3 monthsXx_NEWLINE_xXExperienced clinically relevant coronary artery disease, myocardial infarction within 6 months prior to randomization, uncontrolled congestive heart failure, or symptomatic poorly controlled arrhythmiaXx_NEWLINE_xXCurrent uncontrolled cardiac disease; i.e., uncontrolled hypertension (diastolic blood pressure [BP] > 100 or systolic > 180), unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction (=< 45%); transmural myocardial infarction within the last 6 monthsXx_NEWLINE_xXHistory or current symptoms of congestive heart failure (shortness of breath, ankle swelling)Xx_NEWLINE_xXThe patient has a history of congestive heart failure, coronary artery disease or previous myocardial infarction.Xx_NEWLINE_xXCardiovascular Acute myocardial infarction Congestive heart failure - (NYHA criteria for uncontrolled) Clinically significant cardiac arrhythmias - uncontrolledXx_NEWLINE_xXClinical diagnosis of congestive heart failure and/or pulmonary capillary wedge pressure >15 mmHg, or uncorrected congenital heart disease.Xx_NEWLINE_xXPatients who have had myocardial infarction, severe congestive heart failure, or significant arrhythmia within the past 6 months.Xx_NEWLINE_xXSerious illnesses, such as: cardiovascular disease (uncontrolled congestive heart failure, hypertension, cardiac ischemia, myocardial infarction, severe cardiac arrhythmia), bleeding disorders, autoimmune diseases, severe obstructive or restrictive pulmonary diseases, active systemic infections, inflammatory bowel disorders, severe renal diseaseXx_NEWLINE_xXNo clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months prior to study entryXx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:\r\n - Symptomatic congestive heart failure of New York heart Association Class III or IV \r\n - Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease\r\n - Severely impaired lung function\r\n - Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN (Note: Optimal glycemic control should be achieved before starting trial therapy)\r\n - Active (acute or chronic) or uncontrolled severe infections\r\n - Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C)Xx_NEWLINE_xXUncontrolled hypertension, arrhythmia, congestive heart failure or angina; patients who have had a myocardial infarction or cardiac surgery should be at least 6 months from the event and free of active symptomsXx_NEWLINE_xXUncontrolled medical problems such as diabetes mellitus, coronary artery disease, hypertension, unstable angina, arrhythmias, pulmonary disease, and symptomatic heart failure.Xx_NEWLINE_xXThe patient has a history of congestive heart failure, cor-onary artery disease or previous myocardial infarction.Xx_NEWLINE_xXUnstable systemic disease including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, or myocardial infarction within 6 months before enrollmentXx_NEWLINE_xXCongestive heart failure,Xx_NEWLINE_xXSymptomatic or uncontrolled cardiac failure or coronary artery diseaseXx_NEWLINE_xXUnstable angina or uncontrolled congestive heart failureXx_NEWLINE_xXHistory of myocardial infarction =< 6 months from registration, or congestive heart failure requiring use of ongoing maintenance therapy for life threatening ventricular arrhythmiasXx_NEWLINE_xXElectrocardiogram, showing no indications of cardiac problems like congestive heart failure, myocardial infarction, and cardiomyopathyXx_NEWLINE_xXHistory of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXClinically significant, uncontrolled heart disease (e.g., unstable angina, congestive heart failure, uncontrolled hypertension, ventricular or atrial arrhythmias)Xx_NEWLINE_xXHistory of myocardial infarction =< 6 months prior to registration, unstable angina, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXActive symptomatic congestive heart failureXx_NEWLINE_xXUncontrolled concurrent illnesses, including, but not limited to, active/ongoing infection, symptomatic congestive heart failure, unstable angina pectorisXx_NEWLINE_xXUncontrolled angina within 6 months prior to study entry;Xx_NEWLINE_xXNo history of myocardial infarction =< 6 months prior to registration; no current symptomatic congestive heart failure, uncontrolled angina, or uncontrolled cardiac arrhythmiasXx_NEWLINE_xXHave a known cardiac arrhythmia, uncontrolled congestive heart failure, or acute myocardial infarction within the previous 6 monthsXx_NEWLINE_xXContraindications to a 6-minute walk test as recommended by the American Thoracic Society: (a) acute myocardial infarction (3-5 days), (b) unstable angina, (c) uncontrolled arrhythmias causing symptoms or hemodynamic compromise, (d) frequent uncontrolled syncope, (e) acute endocarditis, (f) acute myocarditis or pericarditis, (g) uncontrolled heart failure, (h) acute pulmonary embolus or pulmonary infarction, (i) acute deep vein thrombosis of lower extremities, (j) suspected dissecting aneurysm, (k) uncontrolled asthma, (l) uncontrolled pulmonary edema, (m) new onset room air desaturation at rest =< 85%, (n) respiratory failure, (o) acute noncardiopulmonary disorder that may affect exercise performance or be aggravated by exercise, (p) mental impairment leading to inability to cooperate, and (q) extensive bone metastases; these contraindications are relative and any concern will be clarified with the treating physician with final approval per their judgementXx_NEWLINE_xXUnstable angina pectoris on medicationXx_NEWLINE_xXCongestive heart failure requiring medication (other than diuretic)Xx_NEWLINE_xXHeart failure exacerbation at the time of study enrollment.Xx_NEWLINE_xXMust not have any of the following absolute contraindications to cardiopulmonary exercise testing and/or aerobic training as determined by the attending oncologist:\r\n* Absolute contraindications\r\n** Acute myocardial infarction (within 3-5 days of any planned study procedures)\r\n** Unstable angina\r\n** Uncontrolled arrhythmia causing symptoms or hemodynamic compromise\r\n** Recurrent syncope\r\n** Active endocarditis\r\n** Acute myocarditis or pericarditis\r\n** Symptomatic severe aortic stenosis\r\n** Uncontrolled heart failure\r\n** Acute (within 3 months) pulmonary embolus or pulmonary infarction\r\n** Thrombosis of lower extremities\r\n** Suspected dissecting aneurysm\r\n** Uncontrolled asthma\r\n** Pulmonary edema\r\n** Room air desaturation at rest =< 85%\r\n** Respiratory failure\r\n** Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e. infection, renal failure, thyrotoxicosis)\r\n** Mental impairment leading to inability to cooperateXx_NEWLINE_xXUnstable anginaXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalitiesXx_NEWLINE_xXHistory of or active ventricular dysrhythmias or congestive heart failure requiring medication or symptomatic coronary heart diseaseXx_NEWLINE_xXUnstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to registration.Xx_NEWLINE_xXExtremity edema due to heart failureXx_NEWLINE_xXPatients with history of congestive heart failureXx_NEWLINE_xXNo absolute contraindications to exercise testing as recommended by the American Thoracic Society; no recent (< 6 months) acute cardiac event unstable angina, uncontrolled dysrhythmias causing symptoms or hemodynamic compromise, symptomatic aortic stenosis, uncontrolled symptomatic heart failure, acute pulmonary embolus, acute myocarditis or pericarditis, suspected or known dissecting aneurism and acute systemic infectionXx_NEWLINE_xXAny significant medical condition that would preclude them from exercising (e.g., congestive heart failure, angina, uncontrolled arrhythmia or other symptoms that indicate increased risk for an acute cardiovascular or respiratory event)Xx_NEWLINE_xXTransmural myocardial infarction, unstable angina, or congestive heart failure requiring hospitalization within the last 6 monthsXx_NEWLINE_xXSevere heart or systemic disease: evidence of documented myocardial infarction, chronic unstable angina, symptomatic congestive heart failure, uncontrolled hypertensionXx_NEWLINE_xXPatient has a serious medical condition (e.g., stroke, liver or renal failure, congestive heart failure, myocardial infarction or cardiac surgery in past year, angina pectoris) that would compromise the safety of the patient or compromise the patient’s ability to complete the study, at the discretion of the investigatorXx_NEWLINE_xXSevere heart or systemic disease: evidence of documented myocardial infarction, chronic unstable angina, symptomatic congestive heart failure, uncontrolled hypertensionXx_NEWLINE_xXMedical history of coronary heart or artery disease, chronic or acute congestive heart failure or history of systolic or diastolic insufficienciesXx_NEWLINE_xXUncontrolled illness, physical disability, or other contraindication to aerobic exercise training including, but not limited to:\r\n* Acute myocardial Infarction (within 5 days of any planned study procedure)\r\n* Unstable angina\r\n* Uncontrolled arrhythmia causing symptoms or hemodynamic compromise\r\n* Recurrent syncope\r\n* Active endocarditis\r\n* Acute myocarditis or pericarditis\r\n* Symptomatic severe aortic stenosis\r\n* Uncontrolled heart failure\r\n* Acute (within 3 months) pulmonary embolus or pulmonary infarction\r\n* Thrombosis of lower extremities\r\n* Suspected dissecting aneurysm\r\n* Uncontrolled asthma\r\n* Pulmonary edema\r\n* Room air desaturation at rest =< 85%\r\n* Respiratory failure\r\n* Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (ie infection, renal failure, thyrotoxicosis)\r\n* Mental impairment leading to inability to cooperateXx_NEWLINE_xXUncontrolled heart failure in the last weekXx_NEWLINE_xXSevere or symptomatic heart diseaseXx_NEWLINE_xXUncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic or decompensated congestive heart failure, cardiac arrhythmia, unstable angina, cirrhosis or renal insufficiency (acute or chronic) on hemodialysis (at the time of diagnosis of AML)Xx_NEWLINE_xXAny of the following contraindications to cardiopulmonary exercise testing:\r\n* Acute myocardial infarction within 3-5 days of any planned study procedures\r\n* Unstable angina\r\n* Uncontrolled arrhythmia causing symptoms or hemodynamic compromise\r\n* Recurrent syncope\r\n* Active endocarditis\r\n* Acute myocarditis or pericarditis\r\n* Symptomatic severe aortic stenosis\r\n* Uncontrolled heart failure\r\n* Acute pulmonary embolus or pulmonary infarction within 3 months of any planned study procedures\r\n* Thrombosis of lower extremities\r\n* Suspected dissecting aneurysm\r\n* Uncontrolled asthma\r\n* Pulmonary edema\r\n* Respiratory failure\r\n* Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e., infection, renal failure, thyrotoxicosis)Xx_NEWLINE_xXSignificant history of uncontrolled cardiac disease defined as uncontrolled hypertension, unstable angina, myocardial infarction within the last 4 months, and uncontrolled congestive heart failureXx_NEWLINE_xXAny of the following absolute contraindications to cardiopulmonary exercise testing:\r\n* Acute myocardial infarction within 3–5 days of any planned study procedures\r\n* Unstable angina\r\n* Uncontrolled arrhythmia causing symptoms or hemodynamic compromise\r\n* Recurrent syncope\r\n* Active endocarditis\r\n* Acute myocarditis or pericarditis\r\n* Symptomatic severe aortic stenosis\r\n* Uncontrolled heart failure\r\n* Acute pulmonary embolus or pulmonary infarction within 3 months of any planned study procedures\r\n* Thrombosis of lower extremities\r\n* Suspected dissecting aneurysm\r\n* Uncontrolled asthma\r\n* Pulmonary edema\r\n* Respiratory failure\r\n* Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e., infection, renal failure, thyrotoxicosis)Xx_NEWLINE_xXCongestive heart failureXx_NEWLINE_xXHistory of myocardial infarction =< 180 days prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiaXx_NEWLINE_xXPatients will be excluded if they have any of the following medical conditions that would prohibit the safe implementation of self-care of LEF: recurrent or metastatic cancer; any other active cancer; acute infection; congestive heart failure; renal failure; cardiac or pulmonary edema; sensitive carotid sinus; severe carotid blockage; and uncontrolled hypertensionXx_NEWLINE_xXCongestive heart failureXx_NEWLINE_xXReceiving treatment for cardiomyopathy or congestive heart failureXx_NEWLINE_xXHistory of congestive heart failure; systolic heart failure defined as ejection fraction (EF) =< 40%, or diastolic heart failure defined as EF > 40% PLUS systemic manifestation of heart failureXx_NEWLINE_xXCongestive heart failure (CHF)Xx_NEWLINE_xXDoes not have clinically significant, symptomatic uncontrolled heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension)Xx_NEWLINE_xXPatients with history of congestive heart failureXx_NEWLINE_xXHistory of any of the following contraindications to oxybutynin:\r\n* Uncontrolled gastroesophageal reflux disease (GERD) despite appropriate therapy; if patient has history of GERD, but symptoms are well-controlled with medical treatment, patient is eligible\r\n* Ulcerative colitis\r\n* Narrow-angle glaucoma\r\n* Urinary retention\r\n* Hypersensitivity to oxybutynin or any other components of the product\r\n* Current uncontrolled hyperthyroidism\r\n* Coronary heart disease (angina or prior myocardial infarction)\r\n* Congestive heart failure\r\n* Symptomatic cardiac arrhythmias\r\n* Current uncontrolled hypertension\r\n* Myasthenia gravis\r\n* DementiaXx_NEWLINE_xXNo pre-existing medical condition(s) that preclude adherence to an unsupervised exercise program (e.g., severe orthopedic conditions, scheduled surgery within 6 months, paralysis and/or dementia, unstable angina, history of myocardial infarction, congestive heart failure) as assessed through oncologist approvalXx_NEWLINE_xXSignificant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screeningXx_NEWLINE_xXNo significant history of a medical problem or co-morbidity that would preclude the patient from undergoing a major abdominal operation such as a history of severe congestive heart failure or active ischemic heart diseaseXx_NEWLINE_xXUnstable cardiac disease, including unstable angina or unstable hypertension, as defined by the need for change in medication for lack of disease control within the last three monthsXx_NEWLINE_xXPatient has significant abnormalities on screening electrocardiogram (EKG) and active and significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, hypertension, valvular disease, pericarditis, or myocardial infarction within 6 months of screeningXx_NEWLINE_xXUnstable angina or uncontrolled congestive heart failureXx_NEWLINE_xXHistory of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmiasXx_NEWLINE_xXAny of the following contraindications to cardiopulmonary exercise testing\r\n* Acute myocardial infarction within 3–5 days of any planned study procedures;\r\n* Unstable angina;\r\n* Uncontrolled arrhythmia causing symptoms or hemodynamic compromise;\r\n* Recurrent syncope;\r\n* Active endocarditis;\r\n* Acute myocarditis or pericarditis;\r\n* Symptomatic severe aortic stenosis;\r\n* Uncontrolled heart failure;\r\n* Acute pulmonary embolus or pulmonary infarction within 3 months of any planned study procedures;\r\n* Thrombosis of lower extremities;\r\n* Suspected dissecting aneurysm;\r\n* Uncontrolled asthma;\r\n* Pulmonary edema;\r\n* Room air desaturation at rest =< 85%;\r\n* Respiratory failure;\r\n* Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e., infection, renal failure, thyrotoxicosis); or\r\n* Mental impairment leading to inability to cooperateXx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions such as:\r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease\r\n* Symptomatic congestive heart failure of New York heart Association class III or IV\r\n* Active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable hepatitis B virus [HBV]-deoxyribonucleic acid [DNA] and/or positive hepatitis B virus surface antigen [HbsAg], quantifiable hepatitis C virus [HCV]-ribonucleic acid [RNA])\r\n* Known severely impaired lung function (spirometry and diffusing capacity of the lung for carbon monoxide [DLCO] 50% or less of normal and oxygen [O2] saturation 88% or less at rest on room air)\r\n* Active, bleeding diathesisXx_NEWLINE_xXDocumentation of congestive heart failure and ejection fraction < 30% if recorded in the pre-operative recordXx_NEWLINE_xXHeart failure exacerbation at the time of enrollmentXx_NEWLINE_xXAny of the following absolute contraindications to cardiopulmonary exercise testing:\r\n* Acute myocardial infarction within 3-5 days of any planned study procedures\r\n* Unstable angina\r\n* Uncontrolled arrhythmia causing symptoms or hemodynamic compromise\r\n* Recurrent syncope\r\n* Active endocarditis\r\n* Acute myocarditis or pericarditis\r\n* Symptomatic severe aortic stenosis\r\n* Uncontrolled heart failure\r\n* Acute pulmonary embolus or pulmonary infarction within 3 months of any planned study procedures\r\n* Thrombosis of lower extremities\r\n* Suspected dissecting aneurysm\r\n* Uncontrolled asthma\r\n* Pulmonary edema\r\n* Room air desaturation at rest =< 85%\r\n* Respiratory failure\r\n* Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e., infection, renal failure, thyrotoxicosis)\r\n* Mental impairment leading to inability to cooperateXx_NEWLINE_xXHeart failure exacerbation at the time of study enrollmentXx_NEWLINE_xXUncontrolled angina, uncontrolled heart failure, or uncontrolled cardiac arrhythmia as determined by the investigator at screening. Subjects with known myocardial infarction within 6 months prior to randomization.Xx_NEWLINE_xXAny patient with known ischemic heart disease, history of congestive heart failure, history of stroke, or cardiac arrhythmia for which the patient requires medication or a medical deviceXx_NEWLINE_xXIf they have angina or unstable coronary diseaseXx_NEWLINE_xXCongestive heart failure refractory to medical managementXx_NEWLINE_xXPatients with pulmonary edema, congestive heart failure or pulmonary embolusXx_NEWLINE_xXNo history of serious cardiac disease that is not adequately controlled; patients with documented myocardial infarction within 6 months prior to study entry, congestive heart failure, unstable angina, clinically significant pericardial effusion or arrhythmia are ineligible; an electrocardiogram (ECG) must be done within 4 weeks prior to study entry on all patientsXx_NEWLINE_xXPatients with medical conditions (e.g., acute infection, congestive heart failure, renal failure, cardiac or pulmonary edema, sensitive carotid sinus, severe carotid blockage, and uncontrolled hypertension) that would prohibit the safe implementation of home-based self-care of lymphedema will be excludedXx_NEWLINE_xXSerious medical illness, including any of the following: uncontrolled congestive heart failure, uncontrolled angina, myocardial infarction, cerebrovascular event within 6 months prior to study entryXx_NEWLINE_xXParticipants with a concurrent active illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, thyroid storm.Xx_NEWLINE_xXParticipants with a concurrent active illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, thyroid stormXx_NEWLINE_xXHave unstable anginaXx_NEWLINE_xXDiabetes mellitus (insulin, oral, or both), chronic obstructive pulmonary disease, emphysema, reactive airway disease; chronic renal disease; multiple sclerosis; seizure disorder; murmurs; hepatitis; human immunodeficiency virus/acquired immunodeficiency syndrome; congestive heart failure; coronary artery disease; aortic aneurysm; history of coronary artery bypass graft; heart valve issues (prolapse, regurgitation, etc.); tachycardia; bradycardia; history of myocardial infarctionXx_NEWLINE_xXReceiving treatment for cardiomyopathy or heart failureXx_NEWLINE_xXCONTROL (HEALTHY) GROUP: Within the past month:\r\n* Heart attack\r\n* Unstable or stable angina (cardiac chest pain)\r\n* Left main coronary artery disease\r\n* Symptomatic heart failure\r\n* Uncontrolled hypertension (SBP > 180 mm Hg or DBP > 100mm Hg)\r\n* Severe valvular heart disease\r\n* Uncontrolled metabolic disease (diabetes with fasting BS > 300 mg/dl, thyrotoxicosis, myxedema)\r\n* Aortic aneurism (> 45 mm diameter) or aortic dissection\r\n* Uncontrolled slow or fast heart rhythm causing symptoms or hemodynamic compromise\r\n* Hypertrophic obstructive cardiomyopathyXx_NEWLINE_xXAnginaXx_NEWLINE_xXUncontrolled congestive heart failure third-degree atrio-ventricular heart block, active pericarditis or myocarditis, recent embolism, thrombophlebitis, deep vein thrombosis, resting ST displacement (> 3 mm), uncontrolled diabetes, uncontrolled pain, cognitive impairment, history of falls due to balance impairment or lost of consciousnessXx_NEWLINE_xXKnown heart diseaseXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 monthsXx_NEWLINE_xXKnown heart diseaseXx_NEWLINE_xXAny condition that, in the opinion of the investigator, may interfere with the objectives of the study, e.g., any condition requiring the use of prohibited drugs or unstable medical conditions other than AML/MDS, such as a cardiac or neurologic disorder expected to be unstable or progressive during the course of the study (e.g., seizures or demyelinating syndromes, acute myocardial infarction within 3 months of study entry, myocardial ischemia or unstable congestive heart failure, unstable arrhythmias)Xx_NEWLINE_xXHistory of myocardial disease, such as myocarditis, cardiomyopathy, congestive heart failure, ischemic cardiomyopathyXx_NEWLINE_xXSymptomatic uncontrolled coronary artery disease or congestive heart failureXx_NEWLINE_xXAny of the following absolute contraindications to cardiopulmonary exercise testing and/or aerobic training:\r\n* Acute myocardial Infarction (within 3-5 days of any planned study procedures);\r\n* Unstable angina;\r\n* Uncontrolled arrhythmia causing symptoms or hemodynamic compromise;\r\n* Recurrent syncope;\r\n* Active endocarditis;\r\n* Acute myocarditis or pericarditis;\r\n* Symptomatic severe aortic stenosis;\r\n* Uncontrolled heart failure;\r\n* Acute pulmonary embolus or pulmonary infarction within 3 months of any planned study procedures;\r\n* Thrombosis of lower extremities;\r\n* Suspected dissecting aneurysm;\r\n* Uncontrolled asthma;\r\n* Pulmonary edema;\r\n* Respiratory failure;\r\n* Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e. infection, renal failure, thyrotoxicosis)Xx_NEWLINE_xXPatients with evidence/history of cardiac disease including congestive heart failure, symptomatic arrhythmia not controlled by medication, unstable angina or cardiac disease, history of acute myocardial infarction (MI) or cerebrovascular accident (CVA) within the past six monthsXx_NEWLINE_xXAny significant cardiac event(s) within the 12 months prior to registration, such as episode(s) of symptomatic congestive heart failure, myocardial infarction, unstable angina pectoris or persistent, stable angina pectoris, or cardiac arrhythmia requiring medicationXx_NEWLINE_xXPatients with congestive heart failure requiring pharmacological managementXx_NEWLINE_xXSubjects with reported unstable cardiovascular disease (e.g., unstable angina, myocardial infarction within past 6 months, cardiac failure or life-threatening arrhythmia, congestive heart failure) or symptomatic postural hypotension within 6 months before screening;Xx_NEWLINE_xXPatients who have any severe and/or uncontrolled medical conditions such as: \r\n* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction 6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease\r\n* Symptomatic congestive heart failure of New York Heart Association class III or IV\r\n* Active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable hepatitis B virus [HBV]-deoxyribonucleic acid [DNA] and/or positive hepatitis B surface antigen [HbsAg], quantifiable hepatitis C virus [HCV]-ribonucleic acid [RNA])\r\n* Known severely impaired lung function (spirometry and diffusion capacity of the lungs for carbon monoxide [DLCO] 50% or less of normal and oxygen [O2] saturation 88% or less at rest on room air)\r\n* Active, bleeding diathesisXx_NEWLINE_xXSignificant comorbidity: ineligible participants include those with clinically significant and uncontrolled major cardiac, respiratory, renal hepatic, gastrointestinal, hematologic, or neurologic/psychiatric disease or disorder, including, but not limited to: active or uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmias, or any other illness or condition that could exacerbate potential toxicities, confound safety assessment or limit compliance with study requirementsXx_NEWLINE_xXPatients with unstable cardiac status including: 4.1 Unstable angina pectoris on medication 4.2 Patients with documented myocardial infarction within 40 days prior to enrollment 4.3 Congestive heart failure NYHA class IV 4.4 Patients with unstable arrhythmia status, already on anti-arrhythmic drugsXx_NEWLINE_xXParticipant reported history of congestive heart failureXx_NEWLINE_xXCongestive heart failureXx_NEWLINE_xXLiver impairment or congestive heart failureXx_NEWLINE_xXHistory of coronary artery disease, including myocardial infarction, congestive heart failure (left ventricular [LV] ejection fraction < 50% or clinically significant diastolic dysfunction), or any serious medical condition which would preclude a patient from undergoing a bronchoscopy or would jeopardize the goals of the studyXx_NEWLINE_xXHas an active infection (e.g., pneumonia), congestive heart failure, bradyarrhythmia, any uncontrolled disease (e.g., diabetic ketoacidosis, gastrointestinal obstruction) except for malignancyXx_NEWLINE_xXUnstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ?6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac diseaseXx_NEWLINE_xXPatients with a history of hypercalcemia or vitamin D toxicity, or hospitalization for treatment of angina, myocardial infarction, or congestive heart failure or psychiatric illness currently or within 30 days of study entry as determined by the investigator.Xx_NEWLINE_xXcongestive heart failureXx_NEWLINE_xXunstable angina,Xx_NEWLINE_xXuncontrolled symptomatic heart failure,Xx_NEWLINE_xXMyocardial infarction (MI); cerebrovascular accident (CVA); uncontrolled congestive heart failure (CHF); significant liver disease; or unstable angina within 6 months prior to enrollmentXx_NEWLINE_xXMyocardial infarction (MI); cerebrovascular accident (CVA); uncontrolled congestive heart failure (CHF); or unstable angina within 6 months prior to enrollmentXx_NEWLINE_xXHistory of renal disease, hypertension, diabetes, congestive heart failure or emphysemaXx_NEWLINE_xXUnstable anginaXx_NEWLINE_xXChest pain, angina, or heart failureXx_NEWLINE_xXUnstable anginaXx_NEWLINE_xXAny other life-threatening illness (e.g. serious, uncontrolled concurrent infection or clinically significant cardiac disease – congestive heart failure, symptomatic coronary artery disease, cardiac arrhythmia not well controlled with medication)Xx_NEWLINE_xXMyocardial infarction (MI); cerebrovascular accident (CVA); uncontrolled congestive heart failure (CHF); significant liver disease; or unstable angina within 6 months prior to enrollmentXx_NEWLINE_xXWorsening of or clinically unstable congestive heart failureXx_NEWLINE_xXUnstable anginaXx_NEWLINE_xXMyocardial infarction (MI); cerebrovascular accident (CVA); uncontrolled congestive heart failure (CHF); or unstable angina within 6 months prior to enrollmentXx_NEWLINE_xXHad within 6 months prior to enrollment: myocardial infarction (MI), cerebrovascular accident (CVA), uncontrolled congestive heart failure (CHF), significant liver disease, unstable anginaXx_NEWLINE_xXPatient has any of the following cardiac abnormalities (as determined by treating Doctor of Medicine [MD]):\r\n* Symptomatic congestive heart failure\r\n* Myocardial infarction =< 6 months prior to enrollment\r\n* Unstable angina pectoris\r\n* Serious uncontrolled cardiac arrhythmia\r\n* Corrected QT interval (QTc) >= 480 msec (>= 500 msec in the presence of right bundle branch block [RBBB])Xx_NEWLINE_xXPatients must not have active significant cardiac disease characterized by symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmiaXx_NEWLINE_xXPatients must not have serious intercurrent illness such as infection requiring IV antibiotics, or significant cardiac disease characterized by significant arrhythmia, ischemic coronary disease or congestive heart failureXx_NEWLINE_xXUnstable cardiac disease, e.g., unstable angina, congestive heart failure or myocardial infarction within the preceding 6 monthsXx_NEWLINE_xXMyocardial infarction (MI); cerebrovascular accident (CVA); uncontrolled congestive heart failure (CHF); significant liver disease; or unstable angina within 6 months prior to enrollmentXx_NEWLINE_xXCongestive heart failure, clinically significantXx_NEWLINE_xXHistory of congestive heart failureXx_NEWLINE_xXSignificant history of uncontrolled cardiac disease defined as uncontrolled hypertension, unstable angina, myocardial infarction within the last 4 months, and uncontrolled congestive heart failureXx_NEWLINE_xXEXCLUSION CRITERIA - FOR NORMAL HEALTHY FEMALE COHORT: History of hepatic, kidney, lungs, gastrointestinal, epileptic, hematologic or psychiatric disease; hypotension or hypertension, of any etiology, that requires pharmacological treatment; history of myocardial infarction, angina and/or heart failureXx_NEWLINE_xXAcute heart disease or history of heart attack, atrial fibrillation, or anginaXx_NEWLINE_xXEvidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 monthsXx_NEWLINE_xXHistory of clinically significant congestive heart failureXx_NEWLINE_xXParticipants with history of hypertension, congestive heart failure, edema, stroke or other cardiac disease or conditionXx_NEWLINE_xXPatients with history of congestive heart failureXx_NEWLINE_xXSymptomatic congestive heart failure.Xx_NEWLINE_xXMen who have contraindications to exercise based the American College of Sports Medicine 2016 Exercise pre-participation screening criteria and who do not receive a physician clearance to participate in the moderate intensity physical activity with one or more of the following self-reported conditions:\r\n* heart attack\r\n* heart surgery, cardiac catherization, or coronary angioplasty\r\n* pacemaker/implantable cardiac defibrillator/rhythm disturbance\r\n* heart valve disease \r\n* heart failure \r\n* heart transplantation \r\n* congenital heart disease \r\n* diabetes \r\n* kidney (renal) disease\r\n* chest discomfort with exertion \r\n* unreasonable breathlessness \r\n* dizziness, fainting or blackouts \r\n* ankle swelling \r\n* unpleasant awareness of forceful, rapid or irregular heart rate \r\n* burning or cramping sensations in your lower legs when walking short distanceXx_NEWLINE_xXHistory or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year.Xx_NEWLINE_xXThe patient has active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, unstable angina pectoris, or uncontrolled congestive heart failure (NYHA class III and IV)Xx_NEWLINE_xXOther clinically significant heart disease (e.g. congestive heart failure, cardiomyopathy or uncontrolled hypertension)Xx_NEWLINE_xXWith the exception of treatment-naïve elderly AML patients, patients with uncontrolled congestive heart failure (CHF), coronary heart disease (CAD), chronic obstructive pulmonary disease (COPD), or left ventricular ejection fraction (LVEF) of ? 50% are excluded, symptomatic or uncontrolled arrhythmias or on continuous corticosteroids.Xx_NEWLINE_xXUnstable angina and/or congestive heart failure requiring hospitalization within the last 6 monthsXx_NEWLINE_xXHistory of heart diseaseXx_NEWLINE_xXUnstable anginaXx_NEWLINE_xX