Total bilirubin =< 1.5 x normal institutional limits; this will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia [predominantly unconjugated bilirubin] in the absence of evidence of hemolysis or hepatic pathology), who will be allowed in consultation with their physicianXx_NEWLINE_xXTotal bilirubin within normal limits (must be obtained =< 2 weeks prior to randomization)Xx_NEWLINE_xXBilirubin =< 1.5 x institutional upper limits of normal (ULN); if patient has documented Gilbert’s syndrome bilirubin must be < 3 x institutional ULNXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin < 1.5 x upper limits of normal (ULN)Xx_NEWLINE_xXSerum bilirubin =< 1.5 x institutional upper limits of normal (ULN); must be obtained within 28 days prior to registrationXx_NEWLINE_xXWithin 14 days of registration: Bilirubin =< 1.5 x upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin < 1.5 x upper limits of normal (ULN)Xx_NEWLINE_xXRE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Total bilirubin < 1.5 x upper limits of normal (ULN)Xx_NEWLINE_xXCreatinine no greater than the institutional upper limits of normalXx_NEWLINE_xXBilirubin =< 2.0 x upper limits of normal (ULN)Xx_NEWLINE_xXObtained within 14 days prior to treatment start: Magnesium within normal limits for the institution or corrected to within normal limits with supplements before first dose of study medicationXx_NEWLINE_xXObtained within 14 days prior to treatment start: Sodium (NA) within normal limits for the institution or corrected to within normal limits with supplements before first dose of study medicationXx_NEWLINE_xXObtained within 14 days prior to treatment start: Phosphorus within normal limits for the institution or corrected to within normal limits with supplements before first dose of study medicationXx_NEWLINE_xXtotal bilirubin within normal institutional limitsXx_NEWLINE_xXPatients must have serum creatinine =< 2 x institutional upper limits of normal (IULN) within 7 days prior to registrationXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin =< 1.5 x upper limits of normal (ULN) (=< 28 days prior to registration)Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine within 1.5 x the ULN institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limits within 14 days of registrationXx_NEWLINE_xXCreatinine within normal institutional limitsXx_NEWLINE_xXSerum bilirubin =< 2.5 times ULN except for participants who are on atazanavir or indinavir, provided that the participant’s direct bilirubin is within normal institutional limitsXx_NEWLINE_xXCreatinine ? 1.5 x upper limits of normalXx_NEWLINE_xXBilirubin ? 1.5 x upper limits of normalXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXAdequate organ function as defined by System Laboratory Values; Hematologic (Absolute neutrophil count [ANC] >=1.5x10^9/ liter [L], Lymphocyte count >1,000/cubic millimeter [mm^3], Hemoglobin >=9 grams/deciliter [g/dL], Platelets >=100x10^9/L), Hepatic (Total bilirubin <=1.5x upper limit of normal [ULN] [For subjects with Gilbert's Syndrome, only if direct bilirubin <=35%, <=3.0xULN], alanine aminotransferase [ALT] <=1.5xULN); Renal (Serum Creatinine <=1.5xULN OR Calculated creatinine clearance [CrCl >50 mL/min) and Endocrine (Thyroid stimulating hormone [TSH] within normal limits. If TSH is not within normal limits at baseline, the subject may still be eligible if total T3 or free T3 and free T4 are within the normal limits.Xx_NEWLINE_xXTotal bilirubin within normal institutional limits (or < 2 X the upper limit of normal in those with Gilbert’s disease)Xx_NEWLINE_xXTotal bilirubin within normal laboratory limitsXx_NEWLINE_xXCreatinine within normal laboratory limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin =< upper normal institutional limitsXx_NEWLINE_xXCreatinine =< upper normal institutional limitsXx_NEWLINE_xXPIK3CA WILD TYPE COHORT (closed 03/17/2016): Total bilirubin =< upper normal institutional limitsXx_NEWLINE_xXENDOCRINE RESISTANT AND ADJUVANT COHORT: Total bilirubin =< upper normal institutional limitsXx_NEWLINE_xXENDOCRINE RESISTANT COHORT: Creatinine =< upper normal institutional limitsXx_NEWLINE_xXBilirubin should be within normal limits (CTCAE v4.0, grade 1)Xx_NEWLINE_xXFree T4 within institutional normal limits.Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine within normal institutional limitsXx_NEWLINE_xXTotal serum bilirubin within normal institutional limitsXx_NEWLINE_xXSerum creatinine within normal institutional limits ORXx_NEWLINE_xXCreatinine within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXWithin 2 weeks prior to initiation of study treatment: Total bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin =< 1.5 x upper limits of normal (ULN)Xx_NEWLINE_xXCreatinine within institutional normal limitsXx_NEWLINE_xXBilirubin must be within or below normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within 1.5 times normal institutional limitsXx_NEWLINE_xXTotal Ca (corrected for serum albumin) w/in normal limitsXx_NEWLINE_xXCOHORT I: Total bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin =< 1.5 x the upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin within normal limits;Xx_NEWLINE_xXTotal bilirubin =< 1.5 x the upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limits unless due to Gilbert’s diseaseXx_NEWLINE_xXBilirubin < 1.5 x upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin must be within normal limits.Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXBilirubin =< 1.5 x institutional limitsXx_NEWLINE_xXPART II: PT/PTT =< 1.5 x the upper limits of normalXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine within normal institutional limitsXx_NEWLINE_xXLVEF at or above institutional lower limits of normal (>= 50%), or at least 5% above lower limits of normal if prior anthracycline exposure (by echocardiogram or nuclear scan within 12 weeks of registration)Xx_NEWLINE_xXSerum calcium within normal institutional limitsXx_NEWLINE_xXSerum phosphorus within normal institutional limitsXx_NEWLINE_xXCreatinine within normal institutional limits ORXx_NEWLINE_xXCreatinine within 1.5 x normal institutional limits.Xx_NEWLINE_xXARM I&II: Transaminases =< times above the upper limits of the institutional normalXx_NEWLINE_xXTotal bilirubin within normal institutional limits; in patients with Gilbert’s, ? 3.0 mg/dLXx_NEWLINE_xXTotal bilirubin within 1.5 x the upper limit of normal institutional limits; patients with elevation of unconjugated bilirubin alone, as in Gilbert's disease, are eligible, performed within 14 days prior to day 1 of protocol therapyXx_NEWLINE_xXPTT & INR within institutional limits.Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXNormal organ and marrow function: Leukocytes ? 3000/?L, Absolute neutrophil count ? 1500/?L, Platelets ? 100,000/?L, Total bilirubin within normal institutional limits, unless patient has Gilbert's disease, for which bilirubin must be ? 2.0 x ULN, AST(SGOT)/ALT (SGPT) ? 1.5 x institutional ULN, creatinine < 1.5 x institutional ULNXx_NEWLINE_xXTotal bilirubin =< 1.5 x normal institutional limits; for patients (Pts) with liver metastasis: total bilirubin must be within normal limits; (except patients with Gilbert syndrome, who can have total bilirubin < 3.0 mg/dL)Xx_NEWLINE_xXTotal bilirubin =< 1.5 mg/dL X institutional upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin within 1.5 x normal institutional limitsXx_NEWLINE_xXCreatinine within 1.5 x normal institutional limitsXx_NEWLINE_xXSerum sodium within normal limits or corrected to within normal limits with supplements before starting treatmentXx_NEWLINE_xXPotassium within normal limits or corrected to within normal limits with supplements before starting treatmentXx_NEWLINE_xXMagnesium within normal limits or corrected to within normal limits with supplements before starting treatmentXx_NEWLINE_xXPhosphorus within normal limits or corrected to within normal limits with supplements before starting treatmentXx_NEWLINE_xXTotal Bilirubin within normal institutional limitsXx_NEWLINE_xXMagnesium within 0.85 to 1.25 x institutional normal limitsXx_NEWLINE_xXPotassium within institutional normal limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limits 14 days or fewer from registrationXx_NEWLINE_xXTotal bilirubin =< 1.5 X institutional upper limits of normal; total bilirubin > 1.5 X above institutional upper limits of normal will be allowed if direct bilirubin is within normal limits or if patients has a documented history of Gilbert’s diseaseXx_NEWLINE_xXCreatinine within normal institutional limits ORXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXSerum creatinine =< 1.5 x normal institutional limitsXx_NEWLINE_xXserum troponin T levels within normal limits;Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin =< 1.5 x the upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin =< 1.5 x the upper limits of normal (ULN) except for patients with Gilbert’s diseaseXx_NEWLINE_xXTotal bilirubin within 1.5 x normal institutional limitsXx_NEWLINE_xXWithin 14 days of registration: Bilirubin within normal institutional limits (or < 2 X the upper limit of normal (ULN) in those with Gilbert’s disease)Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTo be performed within 10 business days prior to day 1: Total bilirubin within 1.5 x the upper limit of normal institutional limits; patients with elevation of unconjugated bilirubin alone, as in Gilbert's disease, are eligibleXx_NEWLINE_xXCreatinine within normal institutional limits, assessed within 14 days prior to registration ORXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXFor pts with liver metastasis: total bilirubin outside of normal limitsXx_NEWLINE_xXTotal bilirubin outside of normal limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limits unless thought due to hemolysis or to Gilbert’s syndromeXx_NEWLINE_xXPHASE II: Serum creatinine within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine within normal institutional limitsXx_NEWLINE_xXGlucose within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin =< 1.5 X upper limits of normalXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine < 1.5 x institutional upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin within 1.5 x the upper limit of normal institutional limits; patients with elevation of unconjugated bilirubin alone, as in Gilbert's disease, are eligibleXx_NEWLINE_xXTotal bilirubin =< 2.5 X institutional limitsXx_NEWLINE_xXTransaminases =< 2 times above the upper limits of the institutional normalXx_NEWLINE_xXInorganic phosphorus outside of normal limitsXx_NEWLINE_xXCreatinine =< 1.5 X upper limits of normalXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin =< 1.5 x the upper limits of normal (ULN)Xx_NEWLINE_xXNormal serum total bilirubin (lower and upper limits of local Laboratory)Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine within normal institutional limits ORXx_NEWLINE_xXBilirubin within normal limits unless patients has Gilbert’s disease and then bilirubin =< 3 x upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine within normal institutional limits ORXx_NEWLINE_xXTotal bilirubin within normal institutional limits (unless Gilbert’s disease with elevated indirect bilirubin only)Xx_NEWLINE_xXCreatinine within or below normal institutional limitsXx_NEWLINE_xXPHASE I STUDY ELIGIBILITY CRITERIA:\r\nTotal bilirubin =< 1.5 X the normal institutional limitsXx_NEWLINE_xXSerum total bilirubin > 2.0 and/or serum transaminases > 3 X the upper limits of normalXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXBilirubin < 1.5 x institutional normal for ageXx_NEWLINE_xXTotal bilirubin within normal institutional limits, determined within 14 days of registrationXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXBilirubin >= 2 x institutional upper limit of normal\r\n* Total bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine within normal institutional limits ORXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXNewly diagnosed MCL: Uric acid within normal limits (allopurinol is allowed to bring abnormal level to within normal limits)Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin < 1.5 x the upper limits of institutional normalXx_NEWLINE_xXBilirubin =< 1.5 x institutional normal for ageXx_NEWLINE_xXTotal bilirubin =< 1.5 X normal institutional limits (within 2 weeks prior to radiotherapy)Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limits (except for participants with Gilbert’s disease)Xx_NEWLINE_xXWithin 4 weeks of preregistration: Total bilirubin =< upper normal institutional limits (except for patients with Gilbert’s disease who are eligible despite elevated serum bilirubin level)Xx_NEWLINE_xXELIGIBILITY CRITERIA FOR REGISTRATION: total bilirubin =< upper normal institutional limits (except for patients with Gilbert’s disease who are eligible despite elevated serum bilirubin level) (within one week of registration if patient postop, otherwise within two weeks of registration)Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXBilirubin =< 1.5x institutional normal for ageXx_NEWLINE_xXProthrombin time (PT) within normal limits or planned and feasible to be corrected to normal limits prior to vertebroplastyXx_NEWLINE_xXPartial thromboplastin time (PTT) within normal limits or planned and feasible to be corrected to normal limits prior to vertebroplastyXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXThyroid function is within normal limitsXx_NEWLINE_xXTotal bilirubin =< 1.5 x normal institutional limits; this last criterion will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia [predominantly unconjugated bilirubin] in the absence of evidence of hemolysis or hepatic pathology), who will be allowed in consultation with their physicianXx_NEWLINE_xXTotal bilirubin within normal limitsXx_NEWLINE_xXCreatinine within normal limitsXx_NEWLINE_xXTotal bilirubin within institutional normal rangeXx_NEWLINE_xXtotal bilirubin within normal institutional limitsXx_NEWLINE_xXTroponin blood level within normal limits.Xx_NEWLINE_xXSerum total bilirubin =< 2X the upper limits of normal (ULN).Xx_NEWLINE_xXTSH within normal limits at baseline, (if not WLN, then total T3 or free T3 and free T4 should be within normal limits) or stable with treatment.Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine within normal institutional limitsXx_NEWLINE_xXUrinalysis within normal institutional limitsXx_NEWLINE_xXTotal bilirubin < 1.5 x the upper limits of institutional normalXx_NEWLINE_xXCardiac function within institutional normal limits on echocardiogramXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine within normal institutional limits ORXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin =< 1.5 x the upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin: within normal limits at each study site local laboratoryXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXPerformed within 14 days prior to study: Bilirubin < 3 times the upper limits of the institutional normalXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine =< 1.5 x upper limits of normalXx_NEWLINE_xXBilirubin =< 1.5 x upper limits of normalXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXDOSE ESCALATION COHORT: Total bilirubin within normal institutional limitsXx_NEWLINE_xXDOSE EXPANSION COHORT: Total bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin up to 1.5 X institutional normal reference rangeXx_NEWLINE_xXAlbumin within normal limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine within normal institutional limits ORXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin < 1.5 x upper limits of normalXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine within normal institutional limits ORXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin =< 2 X normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin < 1.5 x institutional upper limit of normal with direct bilirubin within normal limits except for participants with Gilbert’s diseaseXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXThyroid-stimulating hormone (TSH) within institutional/laboratory normal limitsXx_NEWLINE_xXCreatinine =< 2 x institutional upper limits of normalXx_NEWLINE_xXSerum sodium within normal limitsXx_NEWLINE_xXTotal serum bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limits (unless isolated indirect hyperbilirubinemia due to Gilbert’s disease)Xx_NEWLINE_xXTotal bilirubin within normal limitsXx_NEWLINE_xXTotal bilirubin within normal limitsXx_NEWLINE_xXThyroid stimulating hormone (TSH) within institutional limits (ie: normal); if TSH is greater or less than institutional limits patients may participate if their T4 is within normal limits (WNL); patients may be on a stable dose of replacement thyroid medication; dose adjustments are allowed if neededXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin =< 1.5 x upper limits of normal (ULN)Xx_NEWLINE_xXAspartate aminotransferase (AST) =< 2.5 x upper limits of normal (ULN); for patients with liver metastasis: =< 5 x upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin ? 1.5 x Upper Limits of Normal (ULN)Xx_NEWLINE_xXTotal bilirubin =< 1.5 x the upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin =< normal institutional limitsXx_NEWLINE_xXCreatinine =< normal institutional limits ORXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXBilirubin =< 1.5 x institutional normalXx_NEWLINE_xXTotal bilirubin within normal institutional limits, patients with elevation of unconjugated bilirubin alone, as in Gilbert's disease, are eligibleXx_NEWLINE_xXBilirubin within institutional normal limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limits or < 3 x the upper limit of normal in patients with Gilbert’s diseaseXx_NEWLINE_xXTotal bilirubin ? 1.5 x the upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin within institutional normal limits (or < 2.5 X the ULN for patients with Gilbert’s disease)Xx_NEWLINE_xXBilirubin, AST and ALT not more than 2 x Upper Limits of NormalXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXBilirubin =< 1.5 x upper limits of normal (unless due to liver involvement, hemolysis, or Gilbert’s disease)Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXObtained within 30 days of registration: Total bilirubin within normal institutional limits (may be elevated if direct bilirubin normal)Xx_NEWLINE_xXTotal bilirubin within normal institutional limits within 4 weeks of pre-registrationXx_NEWLINE_xXTotal serum bilirubin within normal limits regardless of liver metastasesXx_NEWLINE_xXTotal bilirubin outside of normal limits; for pts with liver metastasis: total bilirubin outside of normal limitsXx_NEWLINE_xXTotal bilirubin =< 1.5 x the upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXRenal insufficiency: anything over institutional normal limits for creatinine that is also clinically documentedXx_NEWLINE_xXTotal bilirubin must be within 1.5 X the normal institutional limits; if total bilirubin is outside the normal institutional limits, assess direct bilirubinXx_NEWLINE_xXTotal bilirubin =< 1.5 x the upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXThyroid stimulating hormone (TSH) within institutional limits (i.e.: normal); if TSH is greater or less than institutional limits patients may participate if their T4 is within normal limits (WNL); patients may be on a stable dose of replacement thyroid medication; dose adjustments are allowed if needed (labs should be performed within 14 days of treatment initiation)Xx_NEWLINE_xXTotal bilirubin within normal limits, 0–1 mg/dLXx_NEWLINE_xXTotal bilirubin =< 1.5 x the upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin within normal institutional limits (unless known Gilbert’s syndrome)Xx_NEWLINE_xXSerum sodium within normal limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXWithin 14 days of registration: Creatinine within normal institutional limits ORXx_NEWLINE_xXTotal bilirubin =< 2.0 x the upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin =< 1.5 x the upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin =< 1.5 x upper limits of normal (ULN)Xx_NEWLINE_xXBilirubin within the institutional limits of normalXx_NEWLINE_xXPHASE I: Total bilirubin within normal institutional limitsXx_NEWLINE_xXPHASE II: Total bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin up to 1.5 X institutional upper limits of normal (IULN)Xx_NEWLINE_xXCreatinine < 2 x institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXBilirubin =< 1.5 X institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within institutional normal limitsXx_NEWLINE_xXTotal bilirubin within institutional normal limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXObtained within 2 weeks from study entry: Creatinine =< 1.5 X upper limits of normalXx_NEWLINE_xXREGISTRATION INCLUSION CRITERIA: Total bilirubin within institutional upper limits of normal unless related to primary diseaseXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin < 1.5 x normal institutional limitsXx_NEWLINE_xXFree thyroxine (T4) within normal limitsXx_NEWLINE_xXCreatinine within normal institutional limits ORXx_NEWLINE_xXSerum bilirubin > 1.5 x upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin =< institutional upper limits of normalXx_NEWLINE_xXtotal bilirubin <1.5X upper limits of normalXx_NEWLINE_xXcreatinine within normal institutional limits ORXx_NEWLINE_xXTotal bilirubin =< 1.5 x institutional limits unless documented Gilbert's syndrome (then < 2.5 x institutional upper limit)Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine < 1.5 x institutional upper limits of normalXx_NEWLINE_xXLiver function tests >= 2 times the institutional upper limits of normalXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXObtained within 14 days prior to registration: Bilirubin within the institutional limits of normalXx_NEWLINE_xXTotal bilirubin =< 2 X institutional upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin =< 1.5 x normal institutional limitsXx_NEWLINE_xXCreatinine =< 2 x normal institutional limitsXx_NEWLINE_xXTotal bilirubin =< 1.5 x normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin =< 1.5 X normal institutional limitsXx_NEWLINE_xXEXPANSION COHORT ONLY: Total bilirubin =< 1.5 X normal institutional limitsXx_NEWLINE_xXSubject with liver failure as defined by a serum total bilirubin > 2.0 and/or serum transaminases > 3 x the upper limits of normalXx_NEWLINE_xXTroponin T or I within normal institutional limitsXx_NEWLINE_xXBilirubin =< 1.5 x normal limitsXx_NEWLINE_xXSerum creatinine within normal limits within 90 days prior to registrationXx_NEWLINE_xXBilirubin within normal limits within 90 days prior to registrationXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin\r\n* For patients on FOLFIRI, within normal limits\r\n* For patients on FOLFOX, =< 3 X normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXtotal bilirubin within normal institutional limits (or <2X the upper limit of normal in those with Gilbert's disease)Xx_NEWLINE_xXcreatinine within normal institutional limits ORXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin outside of normal limits; for patients (pts) with liver metastasis: total bilirubin outside of normal limitsXx_NEWLINE_xXTotal bilirubin =< 1.5 x the upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin =< 1.5 x the upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCardiac function within institutional normal limits on echocardiogramXx_NEWLINE_xXUric acid within normal limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXSerum creatinine within normal institutional limitsXx_NEWLINE_xXBilirubin within normal institutional limits within 14 days prior to registrationXx_NEWLINE_xXTotal bilirubin within normal limitsXx_NEWLINE_xXTotal bilirubin within normal limitsXx_NEWLINE_xXTroponin I or T within normal limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTREATMENT: Total bilirubin < 1.5 x upper limits of normalXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXSerum total bilirubin is less than or equal to the upper limits of normalXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal limitsXx_NEWLINE_xXElectrocardiogram (ECG) within normal limitsXx_NEWLINE_xXPerformed within 10 days of treatment initiation: Thyroid stimulating hormone (TSH) within institutional limits (ie: normal); if TSH is greater or less than institutional limits patients may participate if their thyroxine (T4) is within normal limits (WNL); patients may be on a stable dose of replacement thyroid medication; dose adjustments are allowed if neededXx_NEWLINE_xXSerum creatinine (Cr) within normal limits (WNL) orXx_NEWLINE_xXTotal bilirubin < 1.5 x within normal institutional limits (unless due to lymphoma involvement of liver or a known history of Gilbert’s disease)Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXElectrolytes within normal limitsXx_NEWLINE_xXInorganic phosphorus outside of normal limitsXx_NEWLINE_xXCoagulation: INR within normal limits, PTT within normal limitsXx_NEWLINE_xXTotal bilirubin must be within 1.5 X the normal institutional limits; if total bilirubin is outside the normal institutional limits, assess direct bilirubin; the direct bilirubin must be within normal parametersXx_NEWLINE_xXTotal bilirubin within normal limitsXx_NEWLINE_xXTotal Bilirubin ? 1.5 x upper limits of normalXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXSerum creatinine within normal limitsXx_NEWLINE_xXTotal bilirubin =< 1.5 x the upper limits of normal (ULN)Xx_NEWLINE_xXTotal serum bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin =< 1.5 x institutional upper limits of normalXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine up to 1.5 X normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXSerum magnesium must be within institutional normal limitsXx_NEWLINE_xXSerum potassium must be within institutional normal limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine within normal institutional limits ORXx_NEWLINE_xXAmylase =< 2 × upper limits of normalXx_NEWLINE_xXHemoglobin within institutional normal limitsXx_NEWLINE_xXPlatelet count within institutional normal limitsXx_NEWLINE_xXAbsolute neutrophil count within institutional normal limitsXx_NEWLINE_xXAbsolute lymphocyte count within institutional normal limitsXx_NEWLINE_xXSerum chemistries within institutional normal limits or requirements for radical prostatectomyXx_NEWLINE_xXRenal panels within institutional normal limits or requirements for radical prostatectomyXx_NEWLINE_xXLiver panels within institutional normal limits or requirements for radical prostatectomyXx_NEWLINE_xXTotal bilirubin < 1.5 x upper limits of normalXx_NEWLINE_xXTotal bilirubin =< 1.5 x upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin =< 1.5 x the upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine within normal institutional limits for ageXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine =< 1.5 x upper limits of normalXx_NEWLINE_xXBilirubin =< 1.5 x upper limits of normalXx_NEWLINE_xXTotal bilirubin =< 1.5 x the upper limits of normal (ULN)Xx_NEWLINE_xXCreatinine within normal limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine =< institutional upper limits of normal (ULN)Xx_NEWLINE_xXUrinary testing results within institutional limits of normal or deemed clinically insignificantXx_NEWLINE_xXPlatelets >= the lower institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine =< the upper institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXThyroid-stimulating hormone (TSH) within normal institutional limitsXx_NEWLINE_xXCreatinine within normal institutional limitsXx_NEWLINE_xXPlatelets within institutional limits of normal or judged to be not clinically significant by the investigatorXx_NEWLINE_xXHemoglobin within institutional limits of normal or judged to be not clinically significant by the investigatorXx_NEWLINE_xXTotal bilirubin within institutional limits of normal or judged to be not clinically significant by the investigatorXx_NEWLINE_xXCreatinine within institutional limits of normal or judged to be not clinically significant by the investigatorXx_NEWLINE_xXTotal bilirubin < 1.5 x upper limits of normalXx_NEWLINE_xXTotal bilirubin < 2.0 x upper limits of normalXx_NEWLINE_xXSerum total bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limits; higher values (=< 3 x institutional upper limit of normal [ULN]) are acceptable in participants with: 1. known or suspected cholangitis associated with Crohn’s disease, or 2, known or suspected inborn errors of metabolism that lead to increased bilirubinXx_NEWLINE_xXCreatinine within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXNormal renal function (defined as creatinine within normal institutional limits)Xx_NEWLINE_xXKnown chronic kidney disease with creatinine greater than normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXRenal insufficiency (i.e., serum creatinine outside of normal limits)Xx_NEWLINE_xXHematocrit within normal institutional limitsXx_NEWLINE_xXPlatelets within normal institutional limitsXx_NEWLINE_xXCreatinine =< the upper institutional limitsXx_NEWLINE_xXCreatinine within institutional normal limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin >= 2 x the upper limits of normal or > 3.0 mg/dl in patients with Gilbert’s syndromeXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXBilirubin > 2.0 x ULN (institutional upper limits of normal)Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXSURGICAL ARM: total bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine clearance within normal limitsXx_NEWLINE_xXBilirubin > 2 x institutional upper limits of normal (ULN), with exception of patients with Gilberts diseaseXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine within normal institutional limitsXx_NEWLINE_xXBilirubin > 1.5 x ULN (institutional upper limits of normal)Xx_NEWLINE_xXBilirubin =< 2.5 x upper limits of normal if no liver metastases present; serum total bilirubin must be =< 3 x upper limits of normal for patients with Gilbert disease; total bilirubin =< 5 x upper limits of normal if liver metastases presentXx_NEWLINE_xXBilirubin > 1.5 x institutional upper limits of normal (ULN)Xx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin < 2 x normal institutional limits or > 3.0 mg/dl in patients with Gilbert’s syndromeXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXCreatinine within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXBilirubin within normal limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXTotal bilirubin within normal institutional limitsXx_NEWLINE_xXtotal bilirubin within normal institutional limitsXx_NEWLINE_xXserum creatinine w/in normal limits orXx_NEWLINE_xXPatients must have the following electrolyte values within normal limits or corrected to be within normal limits with supplements prior to first dose of study medication:Xx_NEWLINE_xXtotal bilirubin within normal institutional limitsXx_NEWLINE_xXtotal bilirubin within normal institutional limits (except in cases of malignant biliary obstruction)Xx_NEWLINE_xX