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+Prior liver transplant
+Cholestatic disorders or unresolved veno-occlusive disease of the liver.
+Clinically important history of liver disease, including viral or other hepatitis or cirrhosis
+Serum creatinine < 2 mg/dl; NOTE: the above stipulation for normal hepatic function does not apply if liver dysfunction is due to leukemia infiltration
+Total bilirubin < 1.5 x upper limit of normal (ULN) if no liver metastases or =< 3 times ULN in the presence of documented Gilbert’s syndrome (unconjugated hyperbilirubinaemia) or liver metastases within 4 weeks before randomization
+History of liver transplant
+History of pituitary or adrenal dysfunction, active or symptomatic viral hepatitis or chronic liver disease
+Adequate liver function as evidenced by bilirubin less than or equal to 1.5 times the ULN and alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 X ULN (in the case of liver metastases less than or equal to 5 X ULN). In case ALP is greater than 3 X ULN (in the absence of liver metastases) or greater than 5 X ULN (in the presence of liver metastases) AND the participant also is known to have bone metastases, the liver specific ALP must be separated from the total and used to assess the liver function instead of the total ALP
+Patients with Gilbert's syndrome are eligible provided the total bilirubin is =< 3 and the remainder of the liver function tests (ALT, AST, alkaline phosphatase [ALK Phos]) are within the institutional normal range
+Patients must not have a history of chronic liver disease (or cirrhosis)
+Patients has current active hepatic or biliary disease (with exception of patients with Gilbert’s syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment)
+Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, or symptomatic biliary disease
+Aspartate aminotransferase (AST) ? 2.5 × ULN without liver metastases; must be ? 5 × ULN with liver metastases
+Alanine aminotransferase (ALT) ? 2.5 × ULN without liver metastases; must be ? 5 × ULN with liver metastases
+Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these
+Patients with a history of venous occlusive disease of the liver
+Participants who have undergone a liver transplant or those who are in the waiting list for liver transplantation
+Pre-existing liver disease
+Alanine aminotransferase (ALT) > 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases, or > 5 times ULN in presence of liver metastases
+Aspartate aminotransferase (AST) > 2.5 times ULN if no demonstrable liver metastases, or > 5 times ULN in presence of liver metastases
+AST < 2.5 x ULN (5.0 x ULN in the presence of liver metastasis)
+ALT < 2.5 x ULN (5.0 x ULN in the presence of liver metastasis).
+Obtained =< 14 days prior to registration: Aspartate transaminase (AST) =< 3 x ULN (=< 5 x ULN for patients with liver involvement)
+Known history of chronic active hepatitis or liver cirrhosis (if suspected by laboratory studies, should be confirmed by liver biopsy).
+Must not have active liver or biliary disease (with the exception of Gilbert’s syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator assessment);\r\n* Note: Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis
+Liver disease characterized by:\r\n* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 x institutional ULN (>= 5 x ULN for subjects with concurrent liver metastasis) confirmed on two consecutive measurements OR\r\n* Absolute impaired excretory function (e.g., hyperbilirubinemia) or synthetic function or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices OR\r\n* Impaired excretory function (e.g., hyperbilirubinemia) or synthetic function or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices OR\r\n* Acute viral or active autoimmune, alcoholic, or other types of acute hepatitis
+Liver function abnormalities as indicated by ongoing hepatic enzyme elevation (AST or ALT) >2 times upper limit of normal (ULN)
+AST and ALT must be less than or equal to 2.5 x ULN for the lab with the following exception: for patients with documented liver metastases, AST and ALT must be less than or equal to 5 x ULN.
+ALP, ALT, and AST > 3 x ULN (>5 x ULN if subject has liver metastases)
+Patients must exhibit adequate bone marrow, liver, and renal function, within 14\r\ndays prior to registration, defined as: \r\n* Absolute neutrophil count (ANC) >= 1,000/mm^3 (growth factor support is permitted)\r\n* Platelets >= 100,000/mm^3 (may be reached by transfusion)\r\n* Hemoglobin >= 10 gm/dl (may be reached by transfusion)\r\n* Glutamate pyruvate transaminase (GPT)/glutamate oxaloacetate transaminase (GOT) < 3 x upper limit of normal (ULN) (or < 5 x ULN in case of liver metastasis)\r\n* Bilirubin < 3 x ULN (or < 5 x ULN in case of liver metastasis)\r\n* Creatinine < 1.5 x ULN
+Liver MRI (? 90 days prior to initiation of transplant conditioning) to document hepatic iron content is required for participants who are currently receiving ?8 packed red blood cell transfusions for ?1 year or have received ?20 packed red blood cell transfusions (cumulative). Participants who have hepatic iron content ?7 mg Fe/ g liver dry weight by liver MRI must have a liver biopsy and histological examination/documentation of the absence of cirrhosis, bridging fibrosis and active hepatitis (? 90 days prior to initiation of transplant conditioning).
+RANDOMIZED PHASE II CLINICAL TRIAL: Within 10 days of registration: AST (SGOT) and ALT (SGPT) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases
+History of chronic liver disease or evidence of hepatic cirrhosis
+Hepatobiliary diseases including biliary tract diseases, autoimmune hepatitis, inflammation, fibrosis, cirrhosis of liver caused by viral, alcohol, or genetic reasons; Gilbert’s disease is allowed if total bilirubin (TBil) is =< 1.5 x ULN
+AST or ALT > 2.5 × ULN. For patients with liver metastasis AST or ALT > 5 × ULN.
+Current active liver or biliary disease.
+Tumor involvement > 50% of the liver
+Cirrhotic liver disease from any cause
+Chronic hepatitis B as defined below or elevated AST, ALT > 3 ULN
+Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involved with lymphoma or stable chronic liver disease per investigator’s assessment)
+Has adequate hepatic function, defined as: AST/ALT levels =< 3 x ULN (if liver metastases are present, =< 5 x ULN) Bilirubin =< 1.5 x ULN.
+AST/ALT =< 2.5 x the IULN or =< 5 x IULN for patients with liver metastases
+Patients with clinical or laboratory evidence of liver disease will need to be evaluated for the cause of the liver disease, its clinical severity in terms of liver function and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dl, or symptomatic biliary disease
+? 3 lesions in the liver
+Total bilirubin < 1.5 times the upper limit of normal (ULN) if no liver metastases or < 3 times the ULN in the presence of documented Gilbert’s syndrome (unconjugated hyperbilirubinemia) or liver metastases
+Subjects with chronic liver disease or dysfunction
+Women with active liver disease or thromboembolic disorder.
+Hepatic metastases on imaging meeting the following criteria:\r\n* Liver-only or liver-dominant metastases, defined as:\r\n** At least 10% liver parenchyma replacement by tumor, but less than 70% replacement of the hepatic parenchyma by tumor\r\n*** For the imaging sub-study: at least one liver lesion must measure greater than 2 cm in size\r\n*** For the imaging sub-study: treatment must only be performed using a single dose, and so arterial variant anatomy that would result in a split treatment will not be allowed\r\n** And, progression of the liver metastases demonstrated within the past twelve months defined as either:\r\n*** Appearance of any new liver lesion or\r\n*** 20% increase in size of at least one liver lesion\r\n** Presence of low-volume extrahepatic lesions (including primary tumor) is allowed if they are asymptomatic\r\n* SUVmax on 68Ga-DOTA-TOC PET of the liver metastases two times greater than the adjacent liver parenchyma
+EXPANDED ACCESS COHORT: AST(SGOT)/ALT(SGPT) =< 2.5 x institutional ULN -OR- AST(SGOT)/ALT(SGPT)\t=< 5 x institutional ULN if liver metastases are present
+Participants with significant renal or liver disease
+History of liver allograft; prior hepatic resection is allowed
+Total bilirubin < 1.5 times the upper limit of normal (ULN) if no liver metastases or < 3 times the ULN in the presence of documented Gilbert’s syndrome (unconjugated hyperbilirubinemia) or liver metastases
+Patients must have radiographically measurable disease (as per Response Evaluation Criteria in Solid Tumors version 1.1 [RECISTv1.1]) in at least one site not previously treated with radiation or liver directed therapy (including bland, chemo- or radio-embolization, or ablation) either within the liver or in a metastatic site
+AST(SGOT)/ALT(SGPT) for patients with documented liver metastases, =< 5 x institutional ULN
+Acute or chronic liver or renal disease
+Has metastatic liver involvement that does not exceed 1/3 of the total liver volume in participants to be treated by liver IT injection. Hepatocellular carcinoma participants are excluded from eligibility of IT liver injection.
+Adequate Liver Function defined as total bilirubin <=1.5 x upper limit of normal (ULN) for age, serum glutamic-pyruvic transaminase (SGPT) Alanine transaminase (ALT) <=2.5 x ULN (for the purpose of this study, the ULN for SGPT is 45 U/L), Serum albumin >=2 g/dL. Must not have active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator assessment). NOTE: Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice, or cirrhosis. No known positivity of hepatitis B surface antigen (HBsAg), or of positive hepatitis C antibody.
+Evidence of renal or liver dysfunction at screening
+Serologically positive for HIV; serologically positive for Hepatitis B or Hepatitis C with evidence of liver dysfunction or documented liver cirrhosis
+Acute or currently active hepatic or biliary disease requiring antiviral therapy (with the exception of Gilbert’s syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment)
+INCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED BY WASH U GPS LABORATORY): AST and ALT: =< 3 x ULN or =< 5 x ULN for patients with liver metastases within 2 weeks of registration
+INCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED AT AN OUTSIDE CLIA CERTIFIED LOCATION): AST and ALT: =< 3 x ULN or =< 5 x ULN for patients with liver metastases within 2 weeks of registration
+EXCLUSION CRITERIA FOR REGISTRATION: Acute or currently active hepatic or biliary disease requiring antiviral therapy (with the exception of patients with Gilbert’s syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment)
+No prior local, liver-directed therapy; prior surgical resection of oligometastatic liver disease is allowed
+History of cirrhotic liver disease
+Known history of chronic liver disease
+Alanine aminotransferase > 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or > 5 times the ULN in the presence of liver metastases.
+Aspartate aminotransferase > 2.5 times the ULN if no demonstrable liver metastases or > 5 times the ULN in the presence of liver metastases.
+Total bilirubin > 1.5 times the ULN if no liver metastases or > 3 times the ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases.
+Clinically significant (as determined by the investigator) hematological, hepatic and renal dysfunction, defined as: Neutrophil count < 1.5 x 10^9/L and platelet count < 100 x 10^9/L; bilirubin > 1.5 x ULN; AST and/or ALT > 2.5 x ULN or > 5 x ULN if patient has documented liver metastases; and serum creatinine > 1.5 x ULN
+Aspartate amino transferase (AST) or Alanine amino transferase (ALT) >3 times ULN in patient without liver metastasis or liver cirrhosis
+Total bilirubin (TBL) < 2x ULN (unless Gilbert's disease or if liver involvement with lymphoma)
+Known clinically significant liver disease, inherited liver disease and active viral disease
+AST ?2.5 x ULN (if liver or bone mets are present, ?5 x ULN)
+ALT ?2.5 x ULN (if liver or bone metastases are present, ?5 x ULN)
+Acute or chronic uncontrolled renal disease, pancreatitis or liver disease (with exception of patients with Gilbert's Syndrome, asymptomatic gall stones, liver metastases, or stable chronic liver disease per investigator assessment)
+AST (SGOT)/ALT (SGPT) ?2 X ULN; ? 5 X ULN if there is liver involvement secondary to tumor
+Intermediate stage HCC (Barcelona Clinic Liver Cancer [BCLC] class B), not eligible for curative treatment, but with Child-Pugh A or B; additionally, tumor cannot involve greater than 50% of the entire liver
+Prior radioembolization to the liver
+Liver transplant
+Aspartate transaminase (AST) =< 3 x ULN, except for patients with liver metastasis, who are included if AST =< 5 x ULN, at the screening visit
+Alanine transaminase (ALT) =< 3 x ULN, except for patients with liver metastasis, who are only included if ALT =< 5 x ULN, at the screening visit
+ALT and/or AST >2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases
+AST or ALT > 2.5 × ULN. For patients with liver metastasis AST or ALT > 5 × ULN
+Any past or present chronic inflammatory colon and/or liver disease, past intestinal obstruction, pseudo or subocclusion or paralysis.
+For subjects with liver metastasis, adequate liver function is demonstrated by serum bilirubin =< 2 x ULN
+For subjects with liver metastasis, adequate liver function is demonstrated by AST/ALT =< 5.0 x ULN
+AST and/or ALT ?2.5× ULN, <5× ULN w/liver metastases
+AST (SGOT)/ALT (SGPT) ?5 X institutional upper limit of normal if with liver metastases; ?2.5 X ULN if no liver metastases
+The presence of known lung or liver metastases greater than 1.0 cm in the long axis diameter
+Aspartate amino-transferase (AST) =< 2.5 x ULN (=< 5 x ULN for subjects with liver involvement of their cancer)
+Chronic liver disease
+Alanine aminotransferase ? 3 x ULN or ? 5 x ULN if liver metastasis is present.
+Have pre-existing alcoholic liver injury or significant liver disease.
+Liver function abnormality; patients who have liver function tests (LFTs) (including total bilirubin, aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) >= twice the upper limit of normal should be evaluated by a gastrointestinal (GI) physician; unless there is a clear precipitating factor (such as an azole, methotrexate, Bactrim or another drug); if the GI physician considers that HCT on the high-intensity arms of protocol is contraindicated for that patient the patient may be considered for treatment on the lower intensity arm of the protocol or excluded from the protocol; patients with Gilbert’s syndrome and no other known liver function abnormality and patients with reversible drug-related transaminitis do not necessarily require GI consultation and may be included on the high-intensity arms of the protocol
+Liver function abnormality; patients who have LFTs >= twice the upper limit of normal should be evaluated by a GI physician unless there is a clear precipitating factor (such as an azole, methotrexate, Bactrim or another drug); patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease will be excluded
+Liver dysfunction (or digestive involvement with protein loss)
+Patients who have severe liver disease including cirrhosis, grade III-IV elevations in liver function studies, or bilirubin in excess of 1.5 mg/deciliter
+Patients with documented liver cirrhosis
+PART II: Alk PO4 =< 3 x ULN (except for patients with documented metastatic disease to bone and/or liver)
+Impaired liver function defined as a total bilirubin > 1.5 x normal range and AST or ALT > 2.5 x normal range unless secondary to Gilbert’s disease, hemolysis or leukemic involvement of the liver
+Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, histology, and the degree of portal hypertension; patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease will be excluded
+AST or ALT > 2.5 x ULN; for patients with liver metastasis AST or ALT > 5 x ULN
+Has a history of liver disease (including but not limited to cirrhosis).
+Prior liver transplant
+Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement or stable chronic liver disease per investigator assessment)
+Presence of symptomatic liver failure including ascites and hepatic encephalopathy
+At least one symptomatic and/or progressive liver lesion over a period of up to 12 months
+Has liver fibrosis either determined by imaging or laboratory testing (i.e. total serum bilirubin > 1.5 times ULN, AST and ALT > 2.5 times ULN, INR > 1.5 times ULN, albumin < 2.5 mg/dl)
+ALT or AST greater than 3.0 times the ULN in the presence of known hepatic metastases
+Alanine aminotransferase (ALT) =< 2.5 x ULN unless demonstrated lymphoma involvement of the liver, performed within 14 days prior to day 1 of protocol therapy
+Total bilirubin < 1.5 times ULN if no liver metastases or < 3 times ULN in the presence of documented Gilbert’s syndrome (unconjugated hyperbilirubinaemia) or liver metastases obtained =< 14 days prior to study initiation
+Liver cirrhosis;
+Total bilirubin >1.5 times ULN if no liver metastases or 3 times ULN in the presence of liver metastases or documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia)
+Active or symptomatic viral hepatitis or chronic liver disease
+Total bilirubin > 1.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or > 3 times ULN in the presence of documented Gilbert’s syndrome or liver metastases
+Liver Transaminases (ALT/AST) ? 2.5 x ULN, ? 5.0 x ULN if liver metastases present
+GENERAL: Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease.
+History of renal or liver transplant
+AST (SGOT)/ALT(SGPT) (only if elevated liver function tests [LFTs] are due to disease) =< 5.0 x institutional upper limit of normal
+Presence of parenchymal liver metastases on imaging
+Active or symptomatic viral hepatitis or chronic liver disease
+Patients with recent (within 60 days preoperatively) history severe hepatic disease (defined as liver injury with encephalopathy plus impaired synthetic liver function (i.e. > 1.5).
+Known clinically significant liver disease, including alcoholic hepatitis, cirrhosis, fatty liver disease, and inherited liver disease
+Liver lesion safely amenable to core needle biopsy.
+Willing to undergo core needle biopsy of liver metastatic site.
+Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease.
+Anticipated liver transplantation
+Patients who have been previously treated with non-SBRT liver directed therapies (with the exception of intrahepatic Y90 infusion) may be enrolled on study; at least 3 months must have elapsed between the most recent liver-directed therapy and study entry
+Any condition that, in the opinion of the investigator, might be significantly exacerbated by the known side effects associated with the administration of pirfenidone e.g., presence of active GVHD of the liver as manifested by rising liver function tests (LFTs) prior to initiation of study treatment
+Uncontrolled adrenal insufficiency or active chronic liver disease
+In patients who have received chronic transfusion therapy for >= 1 year and who have clinical evidence of iron overload by serum ferritin or magnetic resonance imaging (MRI), evaluation by liver biopsy is required; histological examination of the liver must document the absence of cirrhosis, bridging fibrosis and active hepatitis; the absence of bridging fibrosis will be determined using the histological grading and staging scale as described by Ishak and colleagues
+Obtained =< 14 days prior to registration: Aspartate transaminase (AST) =< 2 x ULN (=< 5 x ULN for patients with liver involvement)
+Active or symptomatic viral hepatitis or chronic liver disease.
+Obtained =< 14 days prior to registration: Aspartate transaminase (AST) =< 2.5 x ULN or =< 5 x ULN for subjects with liver metastases
+Active or symptomatic viral hepatitis or chronic liver disease.
+Patient must not be a candidate for liver transplant.
+Significant liver metastasis or disease-related bone pain requiring scheduled narcotics
+Liver function abnormalities: Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, or symptomatic biliary disease
+Liver metastases with no other metastatic sites
+Liver cirrhosis or severe hepatic impairment with function test 3 times above ULN.
+Participants must have biopsy-proven diagnosis of a colorectal cancer with 1-4 liver metastases; there is no upper size limit and participants must have at least 800 mL of uninvolved liver; liver metastases may be diagnosed by imaging alone, no liver biopsy is required; extrahepatic disease is allowed if 1) it has been stable for 3 months prior to study entry, 2) the dominant disease burden is intrahepatic and 3) the patient is referred for definitive radiation therapy to the disease in the liver
+Participants must have liver metastases deemed unresectable due to anatomy, medical fitness, or presence of extrahepatic disease
+Child’s class C liver disease or worse
+Patients with diffuse/multifocal liver involvement are eligible
+Impaired synthetic function or other conditions of decompensated liver disease, such as coagulopathy, hepatic encephalopathy, ascites, and bleeding from esophageal varices
+Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
+Known pre-existing liver disease (e.g. cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, sclerosing cholangitis)
+Current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment)
+Active liver disease, including viral or other hepatitis, or cirrhosis
+Participants with prior Hepatitis B or C infection with inadequate liver function
+Subjects with end-stage kidney disease and/or grade II liver dysfunction
+Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary disease
+Any known active chronic liver disease
+Serum alanine aminotransferase (ALT) =< 2 x UNL or =< 5.0 x UNL in case of liver metastases
+Serum aspartate aminotransferase (AST) =< 2 x UNL or =< 5.0 x UNL in case of liver metastases
+No history of severe prior or ongoing chronic liver disease
+Liver cirrhosis
+Patients who have undergone prior liver transplantation are ineligible
+History of cirrhotic liver disease
+Active acute or chronic GVHD of the liver
+Active viral hepatitis A, B, or C or preexisting or acute liver disease;
+• AST (SGOT) and ALT (SGPT) ? 3 times institutional ULN; if liver metastases are present, then ? 5 times ULN is allowed.
+Any known active chronic liver disease
+Liver cirrhosis or chronic liver disease Child-Pugh B or C
+Patients with greater than 50% liver tumor burden
+Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
+Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
+ALT and AST ? 3 x ULN or ? 5 x ULN if documented liver infiltration with leukemia cells
+Patients with a history of pituitary or adrenal dysfunction or active or symptomatic viral hepatitis or chronic liver disease are not eligible
+Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
+Abnormal liver function tests (LFTs) in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the LFTs as being consistent with hepatic cGVHD and a liver biopsy will not be mandated in this situation
+Patients must have liver-only metastases or predominant liver metastatic disease
+Acceptable liver and renal functions defined as:
+No more than 10 lesions in the liver
+Total bilirubin =< 3 x ULN in patients with documented Gilbert’s syndrome (unconjugated hyperbilirubinemia) or in the presence of liver metastases
+Aspartate amino transferase (AST) or alanine amino transferase (ALT) =< three times the upper limit of (institutional/central) normal (ULN) (if related to liver metastases =< five times ULN)
+Known history of significant liver disease
+Acute or chronic liver disease or severe renal disease considered unrelated to the cancer
+Adequate liver function as demonstrated by: Total bilirubin of ?1.5 mg/dL or ?2.0 mg/dL for subjects with liver metastasis, Alanine aminotransferase (ALT) ?3 x upper limit of normal (ULN) or ?5 x ULN if liver metastasis is present, Alkaline phosphatase ?3 x ULN or ?5 x ULN if bone or liver metastasis is present, Gamma-glutamyl transferase (GGT) <10 x ULN
+Active or symptomatic viral hepatitis or chronic liver disease
+Liver cirrhosis with greater than grade 1 stage 1 inflammation/fibrosis
+Alanine aminotransferase (ALT) >2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases
+Aspartate aminotransferase (AST) >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases
+Patients with Gilbert’s disease and absent hepatic pathology by history and clinical assessment maybe treated on study with bilirubin > the ULN for the institution if other liver function studies are within the normal range
+Known liver disease
+Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator's assessment)
+Subjects with diagnosed active liver disease or with elevation of liver enzymes/bilirubin.
+Patients are excluded if they have liver tumor volume > 50%
+ALT or AST > 1.5 ULN in patients (pts) without liver metastasis
+For pts with liver metastasis: ALT or AST > 2.5 ULN
+Formal evaluation by the Liver Tumor Program at University of Taxes Southwestern (UTSW) and/or review at the Liver Tumor Board: all patients should be fairly and prudently informed of their treatment options; to this end, all patients must be evaluated before brachytherapy treatment for discussion and consideration of other options for treatment of liver cancer including surgical resection
+Patients with a history of prior irradiation or other treatment to the liver or abdomen who after treatment on this protocol would have a cumulative dose to the liver or other normal tissues greater than the protocol defined constraints
+Patients with parahepatic extension of disease with direct non-liver visceral involvement
+=< 3 liver lesions
+Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per treating physician assessment), sources for the determination of clinical significance by the treating physician will be included in the subject’s medical record
+Known history of drug-induced liver injury, alcoholic liver disease, primary biliary cirrhosis, ongoing extra-hepatic obstruction caused by stones, cirrhosis of the liver or portal hypertension
+Obtained =< 14 days prior to randomization: Alanine transaminase (ALT) =< 2.5 x ULN (=< 5 x ULN for patients with liver involvement)
+Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
+Patients who have undergone prior liver transplantation are ineligible
+Uncontrolled adrenal insufficiency or active chronic liver disease
+Alanine aminotransferase > 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases
+Aspartate aminotransferase > 2.5 times ULN if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases
+Total bilirubin > 1.5 times ULN if no liver metastases or > 3 times ULN in the presence of documented Gilbert’s syndrome (unconjugated hyperbilirubinemia) or liver metastases
+Active hepatitis B or C infection with abnormal liver functions (i.e., liver function tests [LFTs] > 2 X upper normal limits)
+Patients must have histologically or cytologically confirmed colorectal cancer with liver metastases deemed resectable by a general or liver surgeon (resectability may involve the use of ablative techniques to some but not all liver metastases); those patients with known disease outside of the liver are not eligible (except for patients with primary lesions in place that are planned for resection or nonspecific lung metastases < 1cm)
+Not have a reported history of liver disease (e.g. cirrhosis)
+Individuals with a reported history of liver disease (e.g. cirrhosis)
+Patients with synchronous or metachronous diagnosis of resectable liver metastases by computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen: a) patients requiring percutaneous or intraoperative ablation of liver metastases < 2 cm in size are eligible; b) patients who underwent prior liver resection or ablation for colorectal liver metastases are eligible
+Aspartate transaminase (AST) =< 3 x ULN, except with liver involvement by the lymphoma who are only included if AST =< 5 x ULN; alanine transaminase (ALT) < 3.0 x ULN, except with liver involvement by the lymphoma who are only included if AST =< 5 x ULN
+If liver metastasis present, then AST/ALT =< 5 x ULN
+Serum aspartate aminotransferases (AST) or alanine aminotransferases (ALT) < 2.5 x IULN for patients without liver metastases; for patients with liver metastases AST or ALT < 5 x IULN is allowed
+ALT/AST ? 2.5 times ULN, or < 5 times ULN for subjects with liver metastases
+Liver enzymes: Aspartate transaminase (AST); Alanine transaminase (ALT) or Alkaline phosphatase (ALP) ?2.5 x ULN (or ?5.0 x ULN if liver involvement by primary disease);
+History of clinically significant liver disease, urea cycle disorder, or genetic liver problem caused by a mitochondrial disorder (e.g., Alpers-Huttenlocher syndrome)
+Pre-existing liver diseases (i.e., cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, and sclerosing cholangitis, etc.)
+Compromised liver function as defined by any of the following:\r\n*  Cohort 1: Advanced cirrhosis group\r\n** Borderline Child-Pugh class A6\r\n** Child-Pugh class B\r\n*** The patients in this advanced cirrhosis group must have at least 400 ml of functional liver, as estimated on either diagnostic imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) or single photon emission computed tomography (SPECT)/CT with Tc-99m sulfur colloid; there is no upper limit on the functional liver volume for these patients\r\n* Cohort 2: Low functional liver volume without underlying chronic liver disease\r\n** Previous irinotecan or oxaliplatin chemotherapy\r\n** Previous liver resection(s)\r\n*** These patients must have at least 400 ml of functional liver, as estimated by either diagnostic imaging computed tomography or magnetic resonance imaging (CT or MRI) or SPECT/CT with Tc-99m sulfur colloid\r\n* Cohort 3: History of prior liver-directed radiation therapy with either fractionated external beam radiation therapy (EBRT), stereotactic body radiation therapy (SBRT) or yttrium-90 radioembolization (Y90 RE); the interval between prior EBRT and re-irradiation on protocol should be equal to or greater than 12 months; the interval between prior Y90 RE and re-irradiation on protocol should be equal to or greater than 6 months; \r\n** Cirrhosis group:\r\n*** Child-Pugh class A5; \r\n*** Borderline Child-Pugh class A6; \r\n*** The patients in this group must have at least 400 ml of functional liver, as estimated on either diagnostic imaging (CT or MRI) or SPECT/CT with Tc-99m sulfur colloid; there is no upper limit on the functional liver volume for these patients\r\n*Low functional liver volume without underlying liver disease\r\n** Previous irinotecan or oxaliplatin chemotherapy\r\n** Previous liver resection(s)\r\n** These patients must have at least 400 ml of functional liver, as estimated by either diagnostic imaging (CT or MRI) or SPECT/CT with Tc-99m sulfur colloid; there is no upper limit on the functional liver volume for these patients
+Tumor replacement =< 50% of total liver volume
+AST or ALT > 3 times ULN, AST or ALT > 5 times ULN for patients with liver metastases.
+Active or symptomatic viral hepatitis or chronic liver disease
+CERITINIB INCLUSION CRITERIA: AST (SGOT) and ALT (SGPT) =< 3 x ULN if no liver metastases are present? =< 5 x ULN if liver metastases are present
+REGORAFENIB INCLUSION CRITERIA: AST (SGOT) and ALT (SGPT) =< 2.5 x ULN if no liver metastases are present? =< 5 x ULN if liver metastases are present
+ENTRECTINIB INCLUSION CRITERIA: AST (SGOT) and ALT (SGPT) =< 3.0 x ULN if no liver metastases are present? =< 5 x ULN if liver metastases are present
+Liver: total bilirubin ? 1.5 x the upper limit of normal (ULN; unless known Gilbert's syndrome); alanine aminotransferase ? 2.5 x ULN (? 5.0 x ULN in patients with liver metastases).
+Active or symptomatic viral hepatitis or chronic liver disease
+Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × ULN (>= 5 × ULN for patients with concurrent liver metastasis); OR impaired excretory function (e.g., hyperbilirubinemia) or synthetic function or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices; OR acute viral or active autoimmune, alcoholic, or other types of hepatitis
+Aspartate transaminase (AST) < 2.0 x ULN, except for patients with liver metastasis, who are only included if AST < 3 x ULN; alanine transaminase (ALT) < 2.0 x ULN, except for patients with liver metastasis, who are only included if ALT < 3 x ULN
+AST and ALT ? 3 x ULN for age unless elevation can be clearly attributed to liver leukemia or metastases
+Prior treatment:\r\n* No prior liver radiation therapy or immunotherapy for cholangiocarcinoma\r\n* Only one previous single agent chemotherapy for ICC allowed\r\n* Patient may have prior liver resection
+In patients with liver metastases, there should be < 50% involvement of the liver
+Alanine transaminase (ALT) ?2.5 × ULN, or ?5 × ULN if leukemic infiltration of the liver is present
+Aspartate transaminase (AST) ?2.5 × ULN, or ?5 × ULN if leukemic infiltration of the liver is present
+No distinction should be made between liver dysfunction due to metastases and liver dysfunction due to other causes
+Subjects must have measurable liver tumors that are suitable for injection.
+Liver tumors must not be estimated to invade approximately more than one-third of the liver.
+Pre-existing liver disease
+Major liver vascular invasion
+Patients with parenchymal liver metastases.
+ARM B COHORT 2: AST and ALT =< 2 X ULN; if liver metastases are present then must be < 5 X the ULN
+ARM B COHORT 3: AST and ALT =< 2 X ULN; if liver metastases are present then must be < 5 X the ULN
+PHASE II COLORECTAL CANCER COHORT 6 (MEDI+C ONLY):\r\nAST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal (ULN); for subjects with liver metastases, AST or ALT =< 5 X ULN
+For subjects with liver metastasis, adequate liver function is demonstrated by serum bilirubin =< 2 x ULN and AST/ALT =< 5.0 x ULN
+AST and ALT ? 3 x ULN or ? 5 x ULN for subjects with known liver metastases
+ALT/AST ? 2.5 times ULN, or < 5 times ULN for subjects with liver metastases
+At least one thoracic or liver lesion amenable to radiation, for group 5 we need one area that can safely receive SBRT or WFRT, not restricted to lung or liver sites
+Liver cirrhosis
+Known (and biopsy-confirmed) liver cirrhosis; or, a reported history of liver cirrhosis with a model for end-stage liver disease (MELD) score > 20
+Adequate liver function with serum AST, ALT and bilirubin within the normal range at the time of crenolanib commencement
+Known significant liver disease including viral, alcoholic, active hepatitis B or C, and/or cirrhosis
+Adequate liver function, as defined by AST and ALT ? 3 x ULN, and bilirubin ? 1.5 x ULN (unless documented Gilbert's syndrome).
+Bilirubin < 1.5 x normal except in cases where abnormal liver function tests (LFTS) are due to involvement with T-NHL
+Patients with clinically important history of liver disease, including viral or other hepatitis or cirrhosis are ineligible
+Patients with liver cirrhosis or other serious active liver disease or with suspected alcohol abuse
+Aspartate transaminase (AST) =< 3.0 x ULN, except for patients with liver metastasis, who are only included if AST =< 5 x ULN; alanine transaminase (ALT) < 3.0 x ULN, except for patients with liver metastasis, who are only included if ALT < 5 x ULN
+History of severe kidney disease (e.g chronic or acute kidney failure) with creatinine clearance below 30 and/or severe liver disease with liver tests over 4 times the upper normal level
+PART 2: Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease will be excluded
+Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
+Liver dysfunction and/ or cirrhosis
+Tumor involving > 50% of the liver
+Liver transplant.
+Patients with acute or chronic liver, renal disease or pancreatitis
+Is scheduled for liver transplantation
+Active liver disease (i.e., cirrhosis, viral or autoimmune hepatitis, etc.)
+Other serious medical conditions that may be expected to limit life expectancy to less than 2 years (e.g., liver cirrhosis).
+Patients must have adequate hepatic function as evidenced by AST and ALT values ? 3 X ULN (? 5 X ULN if the liver is known to be involved by metastatic disease) and serum total bilirubin values of ? 1.5 X ULN for the reference laboratory.
+The patient has a history of liver disease (excluding Gilbert’s disease and non-active hepatitis C) and/or elevation of transaminases or bilirubin above the normal limit
+Patients have known chronic liver disease (i.e., cirrhosis)
+AST/ALT > 2.5-fold above ULN (>5-fold above ULN if liver metastases)
+Prior radiotherapy to the upper abdomen or radioembolization of the liver
+Liver cirrhosis
+For Phase I and II: Adequate liver (bilirubin </=2x ULN, ALT </=2.5x ULN) and renal (creatinine </=2x ULN) function. For patients with suspected liver infiltration from leukemia ALT should be </= 5 ULN.
+Have acute or currently active/requiring anti-viral therapy hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
+Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function and histology, and for the degree of portal hypertension
+Patients with any of the following liver function abnormalities will be excluded:\r\n* Fulminant liver failure\r\n* Cirrhosis with evidence of portal hypertension (ascites or ultrasonographic evidence) or greater than 2+ bridging fibrosis if a liver biopsy is performed based on clinical suspicion (not required for trial)\r\n* Known esophageal varices with or without history or variceal bleed\r\n* Hepatic encephalopathy\r\n* Uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time with international normalized ratio (INR) > 1.5 and not taking anti-coagulation
+Patients with a history of or active liver failure
+Patients who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
+Patient must have disease that is unresectable or borderline resectable with < 70% liver involvement by cancer
+5FU and oxaliplatin are known to be safe to be administered in patients with such abnormal liver function tests
+Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, hepatic involvement by MCL, or stable chronic liver disease per investigator assessment)
+Alanine aminotransferase > 2.5 times upper limit of normal (ULN) if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases; aspartate aminotransferase > 2.5 times ULN if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases
+Total bilirubin > 1.5 times ULN if no liver metastases or > 3 times ULN in the presence of documented Gilbert’s syndrome (unconjugated hyperbilirubinemia) or liver metastases
+Obtained =< 28 days prior to randomization:\r\nAspartate transaminase (AST) =< 2.5 x ULN (or =< 5 x ULN in presence of liver metastases)
+Serum bilirubin < 1.5 mg%, regardless of whether patients have liver involvement secondary to tumor
+Extensive liver tumor burden, defined as more than 75% of the liver
+Histologically confirmed diagnosis of cancer with liver metastases, or histologically confirmed primary liver cancer (e.g. hepatocellular carcinoma, cholangiocarcinoma, or gallbladder carcinoma); subjects may have extrahepatic spread of malignancy, except they may not have brain metastases; subjects with a history of more than one invasive malignancy remain eligible for this study, but in these instances, a liver biopsy is required to document the histology of the liver tumor; an exception to this criterion is made for basal cell carcinoma
+No liver surgery (including radiofrequency ablation), chemotherapy (including bevacizumab), immunotherapy, or liver radiotherapy within 4 weeks of enrollment in this clinical trial
+Prior liver resection of greater than 2 anatomic segments as defined by Couinaud; (subjects that have undergone prior liver wedge excisions or segmental resections are not excluded on this basis alone)
+Patient with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; the patient will be excluded if he/she is found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease
+Adequate hepatic function; patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, histology, and the degree of portal hypertension; patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease will be excluded
+Adequate hepatic function; patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, histology, and the degree of portal hypertension; patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease will be excluded
+No history of severe prior or ongoing chronic liver disease
+Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
+Significant liver, lung, heart, or kidney dysfunction
+Loco-regional therapy to the liver within 28 days before randomization
+Adequate liver function (total bilirubin ?1.5 X ULN (or ?3 X ULN in patients with documented Gilbert's syndrome or for patients with hyperbilirubinemia considered due to myeloid disease), alanine aminotransferase [ALT] and aspartate aminotransferase [AST] ?3 X ULN (or ?5 X ULN for patients with liver involvement of their myeloid disease)
+AST and ALT must be less than or equal to 2.5 x ULN for the lab with the following exception: for patients with documented liver metastases, AST and ALT must be less than or equal to 5 x ULN.
+acute hepatitis, chronic active hepatitis, liver cirrhosis; or an alanine aminotransferase level 3 times or more and/or bilirubin level 2 times or more higher the upper limit of the normal range;
+Non-amyloidosis related chronic liver disease (with the exception of Gilbert's syndrome or clinically asymptomatic gallstones)
+Chronic liver disease or current active liver or biliary disease not attributable to amyloidosis (with the exception of Gilbert's syndrome or asymptomatic gallstones). Exclusion criteria for Group 3
+Chronic liver disease or current active liver or biliary disease not attributable to amyloidosis (with the exception of Gilbert's syndrome or asymptomatic gallstones).
+ALT and AST >3.0 times the ULN if no liver involvement or >5 times the ULN with liver involvement.
+History of chronic liver disease.
+History of chronic liver disease.
+Histologically or cytologically documented locally advanced recurrent or metastatic HCC or for patients with cirrhosis according to the American Association for the Study of Liver Diseases (AASLD) and Asian Pacific Association for the study of the liver (APASL) criteria. Current cirrhotic status of Child Pugh Class A (5-6 points), with no encephalopathy and/or clinically significant ascites (defined as requiring the use of diuretics or paracentesis treatment).
+Known history of drug-induced liver injury, chronic active hepatitis B virus (HBV), chronic active hepatitis C virus (HCV), alcoholic liver disease, non-alcoholic steatohepatitis, cirrhosis of the liver, portal hypertension, primary biliary cirrhosis, or ongoing extrahepatic obstruction caused by cholelithiasis
+Pre-existing liver diseases (i.e. cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, sclerosing cholangitis)
+Liver function tests documented within the screening period and on day -1 of treatment period:
+ALT/AST > UNL or > 2.5 x UNL in case of liver metastases.
+Chronic inflammatory liver condition.
+Patients with acute or chronic liver, renal disease or pancreatitis
+Patients who have current active hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement by CLL, or stable chronic liver disease per investigator assessment) are NOT eligible
+History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)
+Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if subject otherwise meets entry criteria.
+Subjects in Arm A and Arm B should have measurable CT evidence of liver metastases or liver lesions that are not treatable by surgical resection or local ablation in consultation with hepatobiliary specialist.
+Liver tumors must not be estimated to invade approximately more than one-third of the liver.
+Chronic liver dysfunction prior to development of liver metastases (Child-Pugh C or greater).
+Known clinically significant liver disease defined as ongoing drug-induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, portal hypertension, or history of autoimmune hepatitis.
+Serum transaminases =< 3X ULN.\r\n* Note: Transaminases can be up to 5 X ULN in the setting of liver metastases.
+Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, or otherwise stable chronic liver disease per investigator's assessment).
+Ongoing drug-induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), HIV, alcoholic liver disease, non-alcoholic steatohepatitis, cirrhosis of the liver, or portal hypertension
+ALT/AST ? 2.5 times ULN, or < 5 times ULN for subjects with liver metastases
+Severe liver disease
+Severe liver disease
+Adequate renal and hepatic function (creatinine ? 1.5 x IULN, bilirubin within normal limits, AST and ALT ? 3.0 x IULN or 5 x IULN if know liver metastases)
+REGISTRATION TO TREATMENT (STEP 2): AST (SGOT) and ALT (SGPT) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases, within 14 days prior to first dose of pembrolizumab
+Total bilirubin > 3 x ULN unless isolated hyperbilirubinemia is directly related to the acute infection or due to known Gilbert disease; manifestations of end-stage liver disease, such as ascites or hepatic encephalopathy
+Has evidence of significant liver disease
+ENROLLMENT: Adequate liver function, as defined as serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x upper limit of normal (ULN) for age (unless Gilbert’s disease or abnormal liver function due to primary disease).
+Obtained =< 21 days prior to registration: Aspartate transaminase (AST) =< 3 x ULN, =< 5.0 x ULN for patients with metastatic disease to the liver
+Obtained =< 21 days prior to registration: Aminotransferase (ALT) =< 3.0 x ULN, =< 5.0 x ULN for patients with metastatic disease to the liver
+Uncontrolled adrenal insufficiency or active chronic liver disease
+Liver function tests performed within 3 weeks prior to starting study therapy must have alanine aminotransferase and aspartate aminotransferase =< 2.5 x ULN (or =< 5 x ULN if liver metastases are present)
+History or current evidence of malabsorption or liver disease that would impair the absorption of itraconazole
+Note: Patients with liver test abnormalities attributable to hepatic involvement by ALL will be permitted if the total bilirubin is =< 3.0 x ULN and ALT/AST are =< 5.0 x ULN
+Acute or chronic liver disease or severe renal disease considered unrelated to the cancer
+HCC patients only: prior regional treatments for liver metastasis are permitted including:\r\n* Selective internal radiation therapy such as brachytherapy, cyber knife, radiolabeled microsphere embolization, etc.\r\n* Hepatic artery chemoembolization\r\n* Hepatic artery embolization\r\n* Hepatic artery infusional chemotherapy\r\n* Radiofrequency ablation\r\n* NOTE: patients must be >= 4 weeks from treatment and show progressive measurable/evaluable disease in the liver after regional therapy or must have measurable disease outside the liver
+Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
+To be performed within 28 days prior to day 1 of protocol therapy: Aspartate aminotransferase (AST) =< 2.5 x ULN if no liver metastases or =< 5 x ULN if liver metastases
+To be performed within 28 days prior to day 1 of protocol therapy: Alanine aminotransferase (ALT) =< 2.5 x ULN if no liver metastases or =< 5 x ULN if liver metastases
+Prior liver transplant
+Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator assessment).
+Active symptomatic viral hepatitis or chronic liver disease
+History of liver cirrhosis by radiologic, clinical or laboratory data, or biopsy despite normal liver function tests Phase II Expansion Arm A and Arm B:
+History of liver cirrhosis by radiologic, clinical or laboratory data, or biopsy despite normal liver function tests
+ARM A: Disease burden in liver not affecting more than 25% of liver
+ARM B: Disease burden in liver not affecting more than 25% of liver
+DOSE ESCALATION COHORT: \r\n* Note: Subjects with bone metastasis and no liver metastasis on screening image may enroll if ALP is < 5 X ULN; subjects with liver metastasis may enroll if all of AST/ALT/ALP are < 5 X ULN; however, subjects with extensive liver metastasis occupying more than 50% of liver parenchyma will be excluded per epacadostat investigator’s brochure
+DOSE EXPANSION COHORT: \r\n* Note: subjects with bone metastasis and no liver metastasis on screening image may enroll if ALP is < 5 X ULN; subjects with liver metastasis may enroll if all of AST/ALT/ALP are < 5 X ULN; however, subjects with extensive liver metastasis occupying more than 50% of liver parenchyma will be excluded per epacadostat investigator’s brochure
+Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) =< 2.5 x upper limit of normal (ULN) but =< 5.0 x ULN in case of liver metastases; in the presence of liver metastases the liver isoenzyme fraction must be measured and liver isoenzyme fraction (absolute value) must be =< 2 x ULN
+Alkaline phosphatase (ALP) =< 1.5 x ULN but =< 2.5 x ULN in case of liver metastases or =< 5 x ULN in the case of bone metastasis; in the presence of liver metastases the liver isoenzyme fraction must be measured and liver\r\nisoenzyme fraction (absolute value) must be =< 2 x UNL
+Patients with active hepatic or biliary disease (with exception of patients with Gilbert’s syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
+Hepatobiliary diseases including biliary tract diseases, autoimmune hepatitis, inflammation, fibrosis, cirrhosis of liver caused by viral, alcohol, or genetic reasons; Gilbert’s disease is allowed if TBil is =< 1.5 x ULN
+AST/ALT > 2.5 X ULN or > 5 X ULN in the presence of liver metastases; current treatment with anti-androgen is allowed for a maximum of one month to prevent flare response with antiandrogen therapy (ADT)
+Liver: 1000 cGy
+Evidence of liver metastases or visceral disease
+Patients with acute or chronic liver, renal, lung disease or pancreatitis
+Total bilirubin =< 1.5 x ULN; unless presence of Gilbert's syndrome, liver involvement by CLL or MM, or stable chronic liver disease per investigator's assessment
+Liver disease, except Gilbert's syndrome, liver involvement by CLL or MM, or stable chronic liver disease per investigator's assessment
+Previous liver transplantation
+Decompensated liver disease in which pegylated interferon is contraindicated
+If the patient has liver metastases, ALT and AST < 5 x ULN
+Absence of clinically relevant liver or kidney failure as deemed by the treating physician
+Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease
+Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
+Patients who have undergone liver transplantation are excluded
+PHASE II: AST (SGOT) and ALT (SGPT) =< 3 times institutional ULN (=< 5 times if LFT elevations due to known liver metastases)
+Subjects must have adequate organ and marrow function as defined below:\n\n               1. hemoglobin ?9.0 g/dL (?5.6 mmol/L)\n\n               2. white blood cells ?3,000/mm³(?3×10?/L)\n\n               3. absolute neutrophil count ?1,500/mm³ (?1.5×10?/L)\n\n               4. platelets ?100,000/?L (?100×10?/L)\n\n               5. total bilirubin ?1.5× upper limit of normal(ULN)\n\n               6. AST/ALT/AP ?2.5× ULN (ALT/AST ?5.0x ULN in case of documented liver metastases\n\n               7. creatinine ?1.5× ULN\n\n               8. albumin ?3.0 g/dL (?30 g/L)\n\n               9. INR ?1.4
+Patients with acute or chronic liver, renal disease or pancreatitis
+History of liver disease, such as cirrhosis or chronic active hepatitis B and C
+Baseline alanine transaminase (ALT) or aspartate transaminase (AST) > 2 x upper limit of normal (ULN) without known complications of metastatic liver disease or primary hepatic disease (e.g. Cushing’s disease and acromegaly studies)
+Patients with current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
+Patients with clinical or laboratory evidence of liver disease will need to be evaluated for the cause of the liver disease, its clinical severity in terms of liver function and the degree of portal hypertension; patients will be excluded if they are found to have: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dl, or symptomatic biliary disease (Patients will be allowed on to the protocol with liver problems if gastroenterology approves the patient for HCT)
+History or other evidence of decompensated liver disease
+History or other evidence of decompensated liver disease
+Visceral metastasis (excluding liver metastases) and/or lymphadenopathy
+Patient has known chronic liver disease, e.g. diagnosis of chronic active hepatitis or cirrhosis
+Significant gastrointestinal disorder with diarrhea as a major symptom (example Crohn's disease, ulcerative colitis) or grade >= 2 diarrhea of any etiology at baseline; active hepatobiliary disease with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease as determined by investigator's assessment
+Dysfunction of liver (ALT/AST > 5 times normal value, or bilirubin > 3 times normal value), or of renal function (creatinine clearance <30ml/min/1.73m2)
+Liver disease.
+Adequate liver function, defined as normal total bilirubin, ALT ?2.0x ULN, and AST ?2.0x ULN measured within 24 hours prior to crenolanib commencement
+Pre-existing liver diseases (i.e., cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, and sclerosing cholangitis, etc.)
+AST and/or ALT ?5.0 x upper limit of normal (ULN) if liver metastases, or ?3 x ULN without liver metastases
+Must have colorectal cancer with unresectable metastatic disease to the liver (unresectable unilobar or bilobar disease) who have disease progression in the liver with oxaliplatin or irinotecan based first line chemotherapy
+Tumor replacement <50% of total liver volume
+Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ? 3 x ULN (? 5 x ULN if participant has liver metastases). If ALP is > 3 x ULN (in the absence of liver metastases) or > 5 x ULN (in the presence of liver metastases) AND participants are also known to have bone metastases, the liver-specific ALP must be separated from the total and used to assess the liver function instead of the total ALP.
+Ongoing liver injury
+Liver function tests (LFTs) greater than twice the upper limit of normal
+Prior liver transplant
+Patients with known history of liver disorders.
+AST/ALT =< 2.5 x ULN if with liver metastases
+Have had a liver transplant.
+Bilirubin < 2.0 x ULN unless subject has Gilbert’s disease, low-grade hemolysis, or liver involvement with lymphoma
+Organ dysfunction as defined by the following:\r\n* Symptomatic coronary artery disease or cardiac ejection fraction < 35% (or, if unable to obtain ejection fraction, shortening fraction of < 26%); if shortening fraction is < 26% a cardiology consult is required with the principal investigator (PI) having final approval of eligibility; ejection fraction is required if age > 50 years or there is a history of anthracycline exposure or history of cardiac disease\r\n* Diffusing capacity of the lung for carbon monoxide (DLCO) < 35%, TLC < 35%, forced expiratory volume (FEV)1 < 35% and/or receiving supplementary continuous oxygen; the FHCRC PI of the study must approve of enrollment of all patients with pulmonary nodules\r\n* Liver function abnormalities: Patient with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; the patient will be excluded if he/she is found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, or symptomatic biliary disease
+AST (SGOT) and ALT (SGPT): ?2.5xULN OR ?5xULN for subjects with liver metastases
+Patients with known liver disease (alcoholic, drug/toxin induced, genetic, or autoimmune);
+Visceral (ie, liver or lung) metastases as only sites of metastases
+Patients who do not have hepatocellular carcinoma but who have liver lesions or liver metastases may be eligible if they have AST < 3.5 x ULN and AST < 3.5 x ULN if agreed upon by the investigator and medical monitor for the sponsor.
+Patients with Gilbert's syndrome uncomplicated by other liver disease may be eligible if agreed upon by the investigator and medical monitor for the sponsor.
+AST/ALT =< 2.5 x ULN and bilirubin =< ULN for patients with liver metastases
+AST (SGOT) and ALT (SGPT) <2 X institutional ULN (for subjects with hepatic metastases <5 X institutional ULN)
+Acute or chronic liver, pancreatic or severe renal disease
+Patients who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment);
+Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, or symptomatic biliary disease
+AST =< 5.0 x ULN or ALT =< 5.0 x ULN is acceptable if liver has tumor involvement; (Note, if both AST and ALT are done, both must be =< 5.0 x ULN)
+Cancer that has spread to the liver or brain
+known active or symptomatic viral hepatitis, chronic liver disease or liver cirrhosis;
+Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 X ULN (less than or equal to 5 X ULN if participant has liver metastases). If ALP is greater than 3 X ULN (in the absence of liver metastases) or greater than 5 X ULN (in the presence of liver metastases) AND the participant also is known to have bone metastases, the liver-specific ALP must be separated from the total and used to assess the liver function instead of total ALP.
+Alanine aminotransferase (ALT) =< 3.0 x ULN for patients without liver metastases; for patients with liver metastasis ALT =< 5 x ULN is allowed
+AST and/or ALT ?5.0 x upper limit of normal (ULN) if liver metastases, or ?3 x ULN without liver metastases
+AST (SGOT) and ALT (SGPT) ? 2.5 X ULN OR ? 5 X ULN for patients with liver metastases
+Any chronic or concurrent acute liver disease, including viral hepatitis
+Patients with liver metastasis may not be included if AST and/or ALT >5 xULN
+AST/ALT ? 3 x ULN for patients without liver metastasis; ? 5 x ULN for patients with liver metastasis
+Chronic liver disease (e.g., cirrhosis)
+Current active liver or biliary disease.
+AST and ALT ? 3 x ULN (? 5 x ULN if liver is involved by extramedullary hematopoiesis as judged by the investigator or if related to iron chelator therapy that was started within the prior 60 days)
+Subject has had a liver transplant
+AST/ALT ? 5X ULN [with underlying Liver Metastasis]
+Patients with the following organ dysfunction:\r\n* Left ventricular ejection fraction < 35%\r\n* Corrected diffusion capacity of carbon monoxide (DLCO) < 35% or receiving supplemental continuous oxygen\r\n* Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidences by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary disease
+Subjects with known history, or clinical or laboratory evidence of liver disease
+Acute or chronic liver or severe renal disease
+Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
+AST and ALT =< 2.5 x ULN (=< 5 x ULN if liver metastases are present) obtained =< 7 days prior to registration
+Known chronic liver disease, autoimmune hepatitis, or sclerosing cholangitis
+Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; and inherited liver disease
+Liver Transaminases (ALT/AST) ? 2.5 x ULN, ? 5.0 x ULN if liver metastases present
+Liver transaminases within 2.5 times ULN
+Patients have known chronic liver disease (i.e., cirrhosis)
+Hepatobiliary diseases including biliary tract diseases, autoimmune hepatitis, inflammation, fibrosis, cirrhosis of liver caused by viral, alcohol, or genetic reasons; Gilbert’s disease is allowed if TBil is =< 1.5 x ULN
+Patients must have liver metastases.
+ALT or AST > 2.5 ULN in patients (pts) without liver metastasis; for pts with liver metastasis: ALT or AST > 5 x ULN
+Patients must have adequate organ and bone marrow function prior to registration, as defined below: \r\n* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2 x institutional upper         limit of normal (IULN)\r\n* Total bilirubin < 2.0 x IULN (unless Gilbert syndrome has been diagnosed); if leukemia infiltration of the liver is suspected to be causing liver function abnormalities the patient will still be eligible with principal investigator (PI) approval\r\n* Creatinine < 2 x IULN\r\n* Creatinine clearance > 40 mL/min (measured by Cockroft-Gault)
+History of current evidence of malabsorption or liver disease
+Suspected pulmonary and/or liver metastases (greater >= 10 mm in largest axis)
+Acute or chronic liver disease or severe renal disease considered unrelated to the cancer
+Any of the following liver findings: ALT >2.5xULN, ALT > 5xULN with liver metastases/tumor infiltration, Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%), Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator assessment). NOTE: Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices, persistent jaundice or cirrhosis
+Serum transaminases activity =< 2.5 x ULN, with the exception of serum transaminases (< 3 x ULN) if the patient has liver metastases
+Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease
+Chronic liver disease (bilirubin > 1.5 x ULN, ALT or AST > 2 x ULN)
+Liver function abnormalities as indicated by ongoing hepatic enzyme elevation (e.g. AST, ALT, GGT) > 2 x the ULN. Elevation related to direct tumor infiltration is allowed.
+History of clinically significant liver abnormalities other than liver metastasis
+Active liver disease, for example, due to autoimmune hepatic disorder, or sclerosing cholangitis
+Has clearly resectable colon cancer liver metastases (CCLM), for example oligometastatic disease involving only one lobe of the liver. Subjects with suspected resectable CCLM should undergo evaluation by a liver surgeon prior to enrollment to document the incurable nature of their disease.
+For patients with abnormal liver function tests (LFTs) as the sole manifestation of cGVHD, documented GVHD on liver biopsy will be required prior to enrollment; abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with hepatic cGVHD, and a liver biopsy will not be mandated in this situation
+ALT and AST ? 3.0 x ULN (subjects with known liver metastases may have AST and ALT ? 5.0 x ULN)
+For participants with abnormal liver function tests (LFTs) as the sole manifestation of cGVHD, documented GVHD on liver biopsy will be required prior to enrollment; abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with hepatic cGVHD, and a liver biopsy will not be mandated in this situation
+AST/ALT levels ? 2.5 x ULN, or ? 5 x ULN if liver metastases are present.
+Active or symptomatic viral hepatitis or chronic liver disease
+Patients must not have known liver disease such as cirrhosis, decompensated liver disease, active or chronic hepatitis
+Patients with acute or chronic liver, renal disease or pancreatitis
+Alanine transaminase (ALT) =< 3 x ULN (=< 5 x ULN for patients with liver involvement)
+Current active hepatic or biliary disease (with exception of subjects with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment)
+Subjects who have current active hepatic or biliary disease (with exception of participants with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
+Acute or chronic liver or pancreatic disease.
+Alanine aminotransferase (ALT) =< 2.5 x ULN for patients without liver metastases; for patients with liver metastasis ALT =< 5 x ULN is allowed
+Aspartate transaminase (AST) and alanine transaminase (ALT) ? 3 x the upper limit of the normal range (ULN) (? 5 x ULN if liver is involved by extramedullary hematopoiesis as judged by the investigator or if related to iron chelator therapy that was started within the prior 60 days)
+Known active liver disease (cirrhosis, chronic viral hepatitis, autoimmune liver disease or other known clinically significant active liver disease)
+History of chronic liver disease.
+Other serious medical conditions that may be expected to limit life expectancy to less than 1 year (e.g., liver cirrhosis).
+AST level ?2.5 x ULN and ALT ? 2.5 × ULN. For patients with liver metastases, AST ?3.5 x ULN, and AST ?3.5 x ULN may be enrolled if agreed upon by the investigator and medical monitor for the sponsor.
+AST (SGOT) and ALT (SGPT) ? 3.0 x ULN); if liver metastases are present, then ? 5 x ULN is allowed
+Subjects with liver cirrhosis (as determined by the investigator)
+History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)
+Known liver disease, autoimmune hepatitis, or sclerosing cholangitis.
+Total bilirubin >1.5 x ULN if no liver metastases or >3 x ULN in the presence of liver metastases (except in the case of Gilbert's disease)
+Active or symptomatic viral hepatitis or chronic liver disease
+Subjects with inadequate liver (alanine aminotransferase [ALT]/serum glutamate pyruvate transaminase [SGPT] above 4 X upper limit of normal [ULN] or direct bilirubin 4 X ULN AND the lab abnormalities are felt to be due to underlying liver dysfunction)
+Active severe kidney or liver disease
+Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
+A history of cirrhosis or other chronic liver disease
+Active or symptomatic viral hepatitis or chronic liver disease
+Adequate liver function, as evidenced by a serum bilirubin </=2x the ULN (except for patients with a confirmed diagnosis of Gilbert's Disease) and an ALT or AST </=3x the laboratory ULN.
+Pregnant or nursing females 2. HIV or HTLV-1/2 seropositivity 3. Known history of myelodysplasia 4. Known history of chronic active hepatitis or liver cirrhosis (if suspected by laboratory studies, should be confirmed by liver biopsy).
+Patients who have undergone prior liver transplantation are ineligible
+SGOT and SGPT >= 5 x ULN; liver biopsy preferred for such patients
+Hepatic: serum total bilirubin ? 1.5 mg/dL, ALT (SGPT) and AST (SGOT) ?3 x upper limit of normal (ULN) at time of enrollment. If a patient has elevated liver function tests at the time of initial presentation or develops them during work-up and they are the result of a mechanical obstruction of biliary drainage by tumor compression or invasion, a biliary drain may be placed as described in NCCN Practice Guidelines in Oncology V2.2012. If drainage allows for the liver function tests to come within inclusion criteria, the patient may be enrolled.
+Prior liver transplantation and on immunosuppression
+Patients with acute or chronic liver, renal disease or pancreatitis
+Acute or chronic liver disease or severe renal disease considered unrelated to the cancer
+Obtained within 2 weeks from study entry: SGOT, SGPT =< 5 X ULN if liver metastasis present
+Active or severe liver disease (acute or chronic hepatitis, cirrhosis)
+REGISTRATION EXCLUSION CRITERIA: Clinically important history of active liver disease, including viral or other hepatitis or cirrhosis
+Other serious medical conditions that may be expected to limit life expectancy to less than 2 years (e.g., liver cirrhosis).
+Any known active liver disease, e.g. due to HBV, HCV, autoimmune hepatic disorders, or sclerosing cholangitis
+Subjects who have current active hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
+Liver metastases
+Patients with Gilbert’s disease and absent hepatic pathology by history and clinical assessment maybe treated on study with bilirubin > the ULN for the institution if other liver function studies are within the normal range
+Have a history of liver or renal dysfunction
+Current active hepatic or biliary disease (with exception of liver disease secondary to chronic GVHD, or patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment)\r\n* Patients with abnormal liver function tests (bilirubin, alkaline phosphatase, alanine aminotransferase [ALT], aspartate aminotransferase [AST]) due to chronic GVHD are specifically not excluded from the study; this is a common manifestation of chronic GVHD, and thus a major target for the study therapy
+Active chronic liver disease
+Subjects must have no evidence of cirrhosis of the liver; fibrosis of the liver can be tested by Fibroscan or by liver biopsy; these should be performed within approximately a one year period prior to entry onto the study
+Current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
+Patients with a history of pituitary or adrenal dysfunction, active or symptomatic viral hepatitis, or chronic liver disease are not eligible
+ALT =< 2.5 x =< 5 x ULN if liver metastases persist
+Prior liver directed therapies will be permitted (i.e. chemoembolization, radioembolization) as long as target lesions in the liver have demonstrated growth since the liver directed treatment
+Prior peptide receptor radionuclide therapy (PRRT) will be permitted as long as target lesions in the liver have demonstrated growth since the liver directed treatment
+Cirrhosis of the liver
+Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) are ineligible
+Abnormal liver function tests (bilirubin more than 1.5xULRR, and ALT, AST, or ALP more than 2.5xULRR or 5.0xULRR if related to liver metastases).
+Presence of symptomatic liver failure including ascites and hepatic encephalopathy
+Known hepatitis B virus carriers who have liver function tests within the accepted limits are eligible
+Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
+Acute or chronic liver disease or severe renal disease considered unrelated to the cancer
+Active liver disease, including viral or other hepatitis, or cirrhosis
+Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
+For subjects with liver metastases: ALT and AST =< 5 x ULN
+Adequate liver function Total Serum Bilirubin <=1.5 x upper limit of normal (ULN) Transaminases (AST/ALT) <=2.5ULN (if liver metastases are present, then <=5ULN is allowed) ALP <=2.5ULN (if liver and/or bone metastases are present, then <=5ULN is allowed)
+Presence of acute or chronic liver, renal disease, or pancreatitis
+Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary disease
+Current active hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment)
+Patients with liver cirrhosis or any other impaired hepatic function as determined by serum enzymes
+Exception for patients with liver metastasis: ALT (SGPT) =< 8 x ULN
+Active infection (febrile and requiring IV/oral [PO] antibiotics), including hepatitis C or human immunodeficiency virus (HIV), or significant medical illness including renal, cardiac, pulmonary disease, or current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
+Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, or symptomatic biliary disease
+LIVER (ONLY APPLIES TO PATIENTS WITH METASTATIC LIVER LESIONS NOT PREVIOUSLY TREATED WITH RT):
+Patients cannot have more than 3 liver lesions
+Combined diameter of all liver lesions must be =< 6 cm
+Patients with liver metastases cannot have received prior upper abdominal radiation
+AST and ALT ? 3 ULN (? 5 x ULN for subjects with liver metastases)
+Active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
+History of serious liver disease
+d. Liver disease such as cirrhosis of the liver, decompensated liver disease, chronic active hepatitis needing anti-viral therapy
+Current active liver or biliary disease (except Gibler's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease)
+Adequate liver function Total Serum Bilirubin <=1.5 x upper limit of normal (ULN) Transaminases (AST/ALT) <=2.5ULN (if liver metastases are present, then <=5ULN is allowed) ALP <=2.5ULN (if liver and/or bone metastases are present, then <=5ULN is allowed)
+Diagnosis of liver cirrhosis
+Chronic or active hepatitis B or hepatitis C; if questions about liver health, discuss with principal investigator (PI) and strongly consider liver biopsy
+Significant organ dysfunction that would prevent compliance with conditioning, GVHD prophylaxis, or would severely limit the probability of survival:\r\n * 1) Symptomatic coronary artery disease or ejection fraction < 35% or other cardiac failure requiring therapy (or, if unable to obtain ejection fraction, shortening fraction of < 26%); if shortening fraction is < 26% a cardiology consult is required with the principal investigator (PI) having final approval of eligibility\r\n * 2) Diffusion capacity of the lung for carbon monoxide (DLCO) < 40% total lung capacity (TLC) < 40%, forced expiratory volume in one second (FEV1) < 40% and/or receiving supplementary continuous oxygen; the Fred Hutchinson Cancer Research Center (FHCRC) study PI must approve enrollment of all patients with pulmonary nodules\r\n * 3) Liver function abnormalities: patient with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; the patient will be excluded if he/she is found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, or symptomatic biliary disease
+Acute liver disease or previously diagnosed liver tumor (benign or malignant)
+Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary disease
+Adequate bone marrow, liver & renal function as assessed by the following laboratory requirements to be conducted w/in 7 days prior to start of first dose: Hemoglobin >/= 9.0 g/dL; Absolute neutrophil count (ANC) >/= 1,500/mm^3; Platelet count >/= 100,000/mm^3; Total bilirubin </= 1.5 times the upper limit of normal (ULN);ALT and AST </= 2.5 x ULN (</= 5 x ULN for pts w/ liver involvement); INR </= 1.5 and PTT w/in normal limits
+Patient with known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis)
+Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, hepatic damage with bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices or hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dl, or symptomatic biliary disease
+AST and ALT ? 3.0 x ULN or ? 5 x ULN if subject has documented liver metastases
+Serious concurrent medical conditions including: serious heart disease, heart conduction abnormalities, persistent infection, uncontrolled psychiatric illness, liver cirrhosis, chronic liver disease, active or symptomatic viral hepatitis, any other condition that may place the subject at an increased risk or confound the results of the study.
+Has hepatic dysfunction defined as Model for End-Stage Liver Disease (MELD) Score >12.
+Ongoing drug-induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
+Subjects with unresolved veno-occlusive disease of the liver.
+Ongoing drug-induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension would be exclusion for idelalisib therapy but ibrutinib would be an option
+Aspartate aminotransferase (AST) =< 2.5 x upper limit of normal, unless liver is involved with disease or a history of Gilbert’s disease
+Preserved liver function
+Presence of advanced liver disease.
+Prior history of chronic liver disease (eg, chronic alcoholic liver disease, autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, hemachromatosis, non-alcoholic steatohepatitis [NASH]).
+Ongoing liver injury
+Ongoing drug-induced liver injury, active hepatitis C, active hepatitis B , alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
+Patient's total bilirubin must be ? 1.5 x ULN. The hepatic requirements are waived for patients with known or suspected liver involvement who would otherwise be eligible. Cardiac Function:
+AST and ALT 3.0 ULN with the following exception: Patients with liver involvement: AST and/or ALT 5 ULN
+Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease
+Ineligible for liver transplantation per institutional criteria:\r\n* Age > 65 \r\n* Biologic model for end-stage liver disease (MELD) score > 22\r\n* Evidence of extrahepatic disease \r\n* Vascular invasion on imaging
+History of chronic liver disease.
+Patients regardless of eligibility to liver transplant, who have a comorbid disease that might preclude completion of study follow-up.
+Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement with NHL or stable chronic liver disease per treating investigator assessment)
+Hepatic: serum total bilirubin ? 1.5 mg/dL, ALT (SGPT) and AST (SGOT) ?3 x upper limit of normal (ULN) at time of enrollment. If a patient has elevated liver function tests at the time of initial presentation or develops them during work-up and they are the result of a mechanical obstruction of biliary drainage by tumor compression or invasion, a biliary drain may be placed as described in NCCN Practice Guidelines in Oncology V2.2012. If drainage allows for the liver function tests to come within inclusion criteria, the patient may be enrolled.
+Hepatic function\r\n* ARM A:\r\n** Liver enzymes (< x 3 upper limit of normal [ULN]),\r\n** Bilirubin (< x 2 ULN) and stable in the 30 days prior to TCD boost\r\n* ARM B: No limitation
+Patients with acute or chronic liver, renal disease or pancreatitis
+Subject has confirmed cholestatic hyperbilirubenemia due to bile duct obstruction. Subjects who have liver dysfunction due to metastasis alone are excluded.
+For patients with tumor involvement of the liver AST or ALT > 5 x ULN
+Patients must have liver-only or liver-predominant disease to be eligible for this study; liver predominant disease is defined dominant metastatic burden in the liver, with extra-hepatic disease that is judged by the investigator as unlikely to be life threatening within 3 months
+Patients with previous chemoembolization to liver metastases
+AST/ALT (SGOT/SGPT) < 2.5 x ULN for the reference laboratory or < 5 x --ULN in the presence of liver metastases
+End-stage liver disease unrelated to tumor
+Ongoing liver injury
+Have been treated with biologics (eg, antibodies targeting VEGFR or EGFR) after liver resection unless the administration of the biologic started prior to liver resection and continued after liver resection only to complete a pre-specified number of cycles.
+Patients with liver metastases that replace greater than 30% of the liver parenchyma
+Signs or symptoms of progressive or uncontrolled liver disease
+Presence of main portal vein invasion by liver cancer
+Significant liver disease or metastatic disease to the liver
+Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
+SELUMETINIB ARM: AST/SGOT or ALT/SGPT > 2.5 x ULN (>= 5 ULN in presence of liver metastases)
+Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
+Hepatobiliary diseases including biliary tract diseases, autoimmune hepatitis, inflammation, fibrosis, or cirrhosis of liver caused by viral, alcohol, or genetic reasons. Gilbert's disease is allowed if total bilirubin is ?1.5 × ULN.
+Patients with abnormal liver function will be eligible and will be grouped according to the criteria described; patients with active hemolysis should be excluded; no distinction will be made between liver dysfunction due to metastases and liver dysfunction due to other causes
+Known history of clinically significant liver disease, including active viral hepatitis and cirrhosis
+No signs of decompensated liver cirrhosis or ascites requiring therapeutic paracentesis
+History of cirrhotic liver disease
+History of liver transplant.
+Known history of clinically significant liver disease, including active viral hepatitis and cirrhosis
+Known history of drug-induced liver injury, chronic active hepatitis B infection, chronic active hepatitis C infection, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver, or portal hypertension
+Acute or current active (requiring anti-viral therapy) hepatic or biliary disease (with the exception of subjects with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
+AST or ALT > 2.5 × ULN. For patients with liver metastasis, AST or ALT > 5 × ULN
+Pre-existing liver disease (e.g. cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, sclerosing cholangitis)
+Ongoing drug-induced liver injury, chronic active Hepatitis C Virus (HCV), chronic active Hepatitis B Virus (HBV), HIV, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension
+Presence of ascites that preclude biopsy of liver lesions.
+Active liver disease with elevated transaminases > 2 x ULN
+Ongoing drug-induced liver injury, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver
+Serum aspartate transaminase (AST) or alanine transaminase (ALT) 2.5 x upper limit of normal (ULN) if no demonstrable liver metastases or 5 x ULN in the presence of liver metastases
+AST and ALT ?2.5 x ULN for subjects without liver metastases and ?3.5 x ULN for subjects with liver metastases
+Patients with > 3 liver metastases at time of enrollment
+AST/SGOT and/or ALT/SGPT > 2.5 x ULN, (> 5 x ULN if liver metastases present)
+Adequate hepatic function as evidenced by: serum total bilirubin ?1.5 × upper limit of normal (ULN), unless considered due to Gilbert's disease, a gene mutation in UGT1A1, or disease involvement, following approval by the Medical Monitor; AST, ALT, ALP ?2.5 × ULN, with the exception of subjects with bone metastases and/or suspected disease-related liver or biliary involvement, where ALP must be ?5 × ULN
+ALT and AST > 2.5×ULN. For patients with documented liver metastases, ALT and AST > 5×ULN.
+Active or symptomatic viral hepatitis or chronic liver disease
+History of liver transplant
+Has adequate hepatic function, defined as: AST/ALT <= 3 X ULN (if liver metastases are present, <= 5 X ULN) Bilirubin <= 1.5 X ULN
+Liver function tests (LFTs) > 2 x nl
+Patients should have hepatic function (alkaline phosphatase, AST and ALT) < ULN and renal functions with serum creatinine - <1.5 x UNL. If a patient has liver metastasis and/or a history of liver disease - they will receive a lower dose of the drug per treatment protocol.
+Had a prior liver transplant or is planned to undergo liver transplant during the study period;
+Known history of clinically significant liver disease, including active viral hepatitis and cirrhosis
+Adequate hepatic function including ALT ? 2.5 x upper limit of normal (ULN) if liver metastasis is NOT present or ? 5 x ULN if liver metastasis is present, and total bilirubin ? 1.5 x ULN.
+Active or symptomatic viral hepatitis or chronic liver disease
+Liver function tests less than 2 x upper limit of normal range (unless related to medications or Gilbert’s disease)
+Patients with known liver metastases
+History of chronic liver disease.
+Four months post liver transplant
+Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator's assessment).
+Active or symptomatic viral hepatitis or chronic liver disease, including Child-Pugh class B and C liver disease
+AST and ALT ? 3 x ULN, except in patients with tumor involvement of the liver who must have AST and ALT ? 5 x ULN.
+History of liver transplant
+Advanced liver disease, including persistent aspartate transaminase (AST), alanine transaminase (ALT), or total bilirubin value >3 × the upper limit of normal, liver biopsy demonstrating cirrhosis, extensive bridging fibrosis, or active hepatitis.
+Liver/renal dysfunction
+Active or symptomatic viral hepatitis or chronic liver disease
+History of chronic liver disease
+Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN) (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement with non-Hodgkin lymphoma [NHL] or stable chronic liver disease per investigator assessment)
+Total bilirubin =< 1.5 x ULN (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement with NHL or stable chronic liver disease per investigator assessment)
+Subjects who have currently active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement with NHL or stable chronic liver disease per investigator assessment)
+Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, or liver metastases).
+Presence of less than 70% liver involvement by cancer
+Adequate liver function defined as: bilirubin (sum of conjugated + unconjugated) <=1.5 x upper limit of normal (ULN) for age, aspartate aminotransaminase (AST) and alanine transaminase (ALT) <=2.5 x ULN; AST/ALT may be <5 x ULN at baseline if disease under treatment involves the liver (requires radiographic confirmation of liver involvement).
+Patients must not have current active hepatic or biliary disease (with exception of patients with Gilbert’s syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment)
+Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, and inherited liver disease or current alcohol abuse
+Alkaline phosphatase =< 3 ULN; if total ALP is > 3 x ULN (in the absence of liver metastasis) or > 5 x ULN in subjects with liver metastasis AND the subject is known to have bone metastases, then liver ALP iso-enzyme should be used to assess liver function rather than total ALP
+ALT or AST < 2.5 X ULN in the absence of liver metastases
+Active or symptomatic viral hepatitis or chronic liver disease
+Adequate hepatic function, defined as AST and ALT ?3.0X ULN and serum direct bilirubin ?1.5X ULN. Exceptions may be made for patients with elevated liver transaminases secondary to AML after discussion with the Medical Monitor
+Patients with acute or chronic liver, renal disease, or pancreatitis
+Current active liver or biliary disease. Exception: Subjects with Gilbert's syndrome or asymptomatic gallstones, liver metastases related to indolent NHL or otherwise stable chronic liver disease per investigator assessment, are eligible.
+Have hepatocellular cancer, liver cirrhosis with a Child-Pugh stage of B or higher, or have received a liver transplant
+Patients with known liver disease
+History of liver disease, such as cirrhosis or chronic active hepatitis B and C
+Hepatic function: Serum total bilirubin ? 1.5 x ULN (upper limit of normal); AST (SGOT) and ALT (SGPT) ? 3 x ULN, except in patients with tumor involvement of the liver who must have AST and ALT ? 5 x ULN
+Underlying chronic liver disease with evidence of severe liver impairment.
+Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones).
+Patients with acute hepatitis or end stage liver disease
+History or current hepatitis or other liver disease
+History or current evidence of malabsorption or liver disease that would impair the absorption of Itraconazole as measured by liver function tests within the past one year prior to enrollment
+liver, pancreatic or severe renal disease unrelated to disease under study
+Liver Function If bilirubin, AST, and/or ALT are >ULN
+Normal liver function based on Liver Function Tests (Total Bilirubin and AST <1.5 X Upper Limit of Normal).
+Liver cirrhosis with greater than grade 1 stage 1 inflammation/fibrosis
+have acute or currently active/requiring anti-viral therapy hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease);
+Have current active hepatic or biliary disease (with exception of subjects with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
+The participant has adequate hepatic function as defined by a total bilirubin ? 1.5 x the upper limit of normal (ULN), and aspartate transaminase (AST) and alanine transaminase (ALT) ? 3 x the ULN (or ? 5 x the ULN in the presence of known liver metastases)
+Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 x ULN; in patients with significant liver disease and chronically elevated liver transaminases, ALT may be elevated as high as 8 x ULN
+Patients with advanced malignant hepatic tumors (liver metastases that replace more than 30% of the liver parenchyma)
+Active liver disease including cirrhosis or hepatitis
+Alanine amino transferase (ALT) or aspartate amino transferase (AST) greater than 2.5 times the ULRR if no demonstrable liver metastases or greater than 5 times the ULRR in the presence of liver metastases.
+Liver function tests with values > 3 x ULN
+Aspartate transaminase (AST) > 3.0 x ULN, except for patients with liver metastasis who are excluded if AST > 5.0 x ULN
+Alanine transaminase (ALT) > 3.0 x ULN, except for patients with liver metastasis who are excluded if ALT > 5.0 x ULN
+Alanine aminotransferase (ALT) < 2.5 times ULN; in the case of known (radiological and/or biopsy documented) liver metastasis, ALT < 5.0 times ULN is acceptable; patients with > 3 liver metastases at enrollment will be excluded
+Liver metastases
+History of veno-occlusive disease of the liver
+Known history of chronic liver disease (other than Gilbert’s syndrome)
+AST ? 2.5 times ULN (? 5 times ULN for patients with liver metastases);
+Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ?3 × ULN (?5 × ULN if participant has liver metastases). If ALP is >3 × ULN (in the absence of liver metastases) or >5 × ULN (in the presence of liver metastases) AND participants are also known to have bone metastases, the liver-specific ALP must be separated from the total and used to assess the liver function instead of the total ALP.
+Active uncontrolled stage 4 acute liver GVHD prior to administration of ibrutinib
+Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease per investigator assessment).
+Patients with history of severe liver disease, defined as and confirmed by albumin less than 3.
+History of liver disease
+Pre-existing liver disease: elevated international normalized ratio (INR) > 1.4 or elevated transaminase levels, or patient medical history of cirrhosis, or liver disease
+Potential subjects will be excluded for a number of medical conditions that might represent a risk for riluzole (including history of allergic reaction to riluzole and evidence of liver disease) and potentially confound the relationship among CNS glutamate, inflammation and behavior/cognition, including: autoimmune or inflammatory disorders, chronic infectious diseases (e.g. human immunodeficiency virus [HIV], hepatitis B or C), pregnancy, neurologic disorders (including a history of serious head trauma or seizures), liver disease (as manifested as an elevation in liver transaminases), uncontrolled cardiovascular, metabolic, pulmonary or renal disease (as determined by medical history and laboratory testing)
+Chronic liver disease
+Liver tumor burden less than or equal to 70%
+Patients undergoing open elective liver resection for primary liver pathology (benign or malignant) or secondary metastatic liver disease, including patients undergoing concomitant surgical procedures (such as colorectal resection or debulking procedures), with no contraindication to the insertion of an epidural catheter (localized infection, septicemia, or pre-operative coagulopathy)
+Significant liver disease that would inhibit prescription of opioids
+Significant liver metastatic disease interfering with safe/effective percutaneous transhepatic biliary drainage (PTBD).
+Patients must have liver tumors requiring a major liver resection, defined as removing at least three anatomical segments in patients without liver disease and two segments in patients with cirrhosis/fibrosis of the liver
+Clinical indication for a therapeutic liver resection
+No liver failure
+Chronic liver disease or in participants without known liver disease, alanine aminotransferase (ALT) >= 3 x normal
+Participants with end-stage liver disease (cirrhosis)
+Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease (exception for participants in Arm A and Arm F)
+Documented liver disease with marked elevation of transaminases >3 x ULN or,
+Patients with liver cirrhosis
+Liver transplant.
+Patients with underlying liver disease, such as cirrhosis or chronic hepatitis, and do not have primary or metastatic cancer in the liver will be excluded if alanine aminotransferase (ALT)/aspartate aminotransferase (AST) > 3 x upper limit of normal (ULN) or total bilirubin (bili) > 3 x ULN; in the presence of primary or metastatic liver cancer, patients will be excluded if ALT/AST > 5 x ULN or total bili > 5 x ULN
+For participants with abnormal liver function tests (LFTs) as the sole manifestation of cGVHD, documented GVHD on liver biopsy will be required prior to enrollment; abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with hepatic cGVHD, and a liver biopsy will not be mandated in this situation
+Patients with normal hepatic function according to MD Anderson testing standards and no prior liver disease
+No significant synthetic dysfunction of the liver; if there is a question of such, a liver biopsy should be performed for further assessment
+Abnormal liver function (total bilirubin > 2X ULN or liver enzymes alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 2.5X ULN for subjects without liver metastasis or ? 5X ULN for subjects with liver metastasis) as assessed by the central laboratory during screening. Subjects with documented Gilbert's Disease may be eligible.
+History of hepatitis or liver disease
+Patients with liver cirrhosis (as determined by the investigator)
+Diffuse intrahepatic metastases that involves > 10 % of the liver
+For patients with abnormal liver function tests (LFTs) above the thresholds, documented cGVHD on liver biopsy will be required prior to enrollment
+Active or symptomatic viral hepatitis or chronic liver disease
+Able to undergo:\r\n* Percutaneous or transjugular biopsy of cirrhotic liver at least 7 days prior to liver resection (surgical cohort), OR\r\n* A biopsy of the cirrhotic liver (non-surgical cohort)
+Willingness to authorize collection of tissue from surgically-resected liver or clinical liver biopsy for analyses
+Non-surgical cohort only: pathology report from clinical liver biopsy (=< 3 months prior to pre-registration) demonstrates no histologic abnormalities associated with chronic hepatitis, steatohepatitis, fibrosis, or cirrhosis
+History of, or current, active or chronic liver disease even if transaminases have normalized
+Prior liver transplant
+Model for end-stage liver disease (MELD) > 20
+Significant liver disease as defined as aspartate transaminase (AST) or alanine transferase (ALT) twice than normal
+History of severe kidney disease (e.g. chronic or acute kidney failure) with creatinine clearance below 30 and/or severe liver disease with liver tests over 4 times the upper normal level
+Patients with clinical or laboratory evidence of liver disease should be evaluated in conjunction with the gastrointestinal (GI) consult service for the cause of the liver disease, its clinical severity, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, refractory ascites related to portal hypertension, bacterial or fungal liver abscess, chronic viral hepatitis with total serum bilirubin > 3 mg/dl, or actively symptomatic biliary disease
+Prior liver transplant
+Participants with a clinical diagnosis of cirrhosis based on the investigator's evaluation, confirmed by any one of following methods to define cirrhosis:\r\n* Established cirrhosis on liver biopsy (Meta-analysis of Histological Data in Viral Hepatitis [METAVIR] F4);\r\n* Computed tomography (CT) or magnetic resonance imaging (MRI) findings consistent with cirrhosis; nodular appearing liver with or without evidence of portal hypertension\r\n* Transient elastography (FibroScan) with a result > 12.5 kPa\r\n* FibroScan score > 0.75 and aspartate aminotransferase (AST) to platelet ratio index (APRI) > 2\r\n* Etiology of cirrhosis will not be considered in determining inclusion in the study
+Acute or chronic liver disease, evidence of hepatitis (infectious or autoimmune), cirrhosis or portal hypertension
+History of hepatitis or liver dysfunction
+Known chronic liver disease (Child’s B cirrhosis)
+Patients with a history of liver disease or AST/ALT >= 2.5 times ULN on screening
+Acute liver disease, unexplained transaminase elevations, or elevated serum calcium
+Patients with end stage liver disease or anticipated liver transplant within the next two years will be excluded; a history of liver transplant is not an exclusion per se, if patient does not meet stated hepatic criteria
+Patients with history of pituitary or adrenal dysfunction, active or symptomatic viral hepatitis or chronic liver disease are not eligible
+Patients with current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease)
+Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator's assessment).
+AST (SGOT) and ALT (SGPT) ? 2.5 x ULN. For subjects with documented liver metastases, ALT and AST ? 5 × ULN
+Prior radiotherapy to the upper abdomen/liver
+Patients with abnormal liver function will be eligible and will be grouped according to the criteria below\r\n* Group A (normal hepatic function)\r\n** Bilirubin =< upper limit of normal (ULN) and aspartate aminotransferase (AST) =< ULN\r\n* Group B (mild hepatic dysfunction)\r\n** B1: bilirubin =< ULN and AST > ULN\r\n** B2: bilirubin > ULN but =< 1.5 x ULN and any AST\r\n* Group C (moderate hepatic dysfunction)\r\n** Bilirubin > 1.5 x ULN to =< 3 x ULN and any AST\r\n* Group D (severe hepatic dysfunction) \r\n** Bilirubin > 3 x ULN and up to investigators discretion and any AST\r\n* Patients with active hemolysis should be excluded; no distinction will be made between liver dysfunction due to metastases and liver dysfunction due to other causes; registration laboratory investigations will be used to assign a patient to a hepatic function group; liver function tests should be repeated within 24 hours prior to starting initial therapy and may result in the patients' group assignment being altered if different to registration test results
+Subject has known active liver disease, including viral hepatitis or cirrhosis.
+active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease (except for Hep B and Hep C positive patients)
+Patient must NOT be in liver failure as judged by the patient’s physician
+Have known cirrhosis or other risk factors for HCC, based on American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL) guidelines (applicable in each site jurisdictions)
+Individuals with history of liver disease in last 12 months
+- AST and ALT < 2.5 x ULN (< 5 x ULN in patients with known liver metastases)
+Patients in liver failure as judged by the patient’s physician
+Liver metastases on most recent prior M.D. Anderson CT examination.
+Aspartate aminotransferase (AST) =< 2.5 x ULN OR < 5 x ULN for subjects with liver metastases, obtained within 14 days prior to C11-AMT PET scan
+Alanine aminotransferase (ALT) =< 2.5 x ULN OR < 5 x ULN for subjects with liver metastases, obtained within 14 days prior to C11-AMT PET scan
+Patients with liver failure are NOT eligible.
+Patients with primary stage I, II, III liver cancer or metastatic tumor in the liver from any cancer site
+AST/SGOT, ALT/SGPT ?2.5 x ULN, unless liver metastases are clearly present, then ?5.0 x ULN
+Diagnosis of a non-HCC liver mass with one or more of the following:\r\n* Liver mass (>= 1 cm) that has suggestive imaging findings of a benign liver mass (adenoma, hemangioma, focal nodular hyperplasia)\r\n* Liver mass (>= 1 cm) that is biopsy proven metastatic disease (metastatic colorectal cancer, metastatic pancreatic cancer)\r\n* Liver mass (>= 1 cm) that is a non-HCC primary malignancy (cholangiocarcinoma)
+History of liver disease within the last 12 months
+Patient has at least 1 focal lesion in liver
+Patient has:\r\n* Liver lesions that are untreated liver lesions or \r\n* Changing treatment regimen/type and/or receiving a new form of treatment and/or has been on a treatment break (‘holiday’) for liver lesions
+AST and ALT =< 2.5 X ULN or =< 5 x ULN if liver metastases are present (evaluated within 28 days of randomization); concomitant elevations in bilirubin and AST/ALT above 1.0 x ULN are not permitted
+Active or symptomatic viral hepatitis or chronic liver disease
+Patients must have liver-dominant or liver-only metastatic disease from any primary histology; patients with primary hepatocellular or biliary cancer are also eligible
+Patients not undergoing radioembolization to the liver
+Patients with primary or metastatic tumors in the lungs, liver, or pancreas
+Have acute or currently active/requiring anti-viral therapy hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
+ALT/AST ? 2.5 x ULN or ? 5 x ULN if documented liver metastases
+Prior liver transplant
+AST(SGOT)/ALT(SGPT) ?3 X ULN (including patients with liver metastases)
+Aspartate aminotransaminase (AST) =< 2.5 x upper limit of normal (ULN) (=< 5.0 x in case of liver [metastases] mets), within 2 weeks prior to study start
+Patients with confirmed or suspected liver lesions
+Biopsy proven or clinically suspected advanced parenchymal liver disease
+Clinically or radiographically suspected liver damage, hepatic steatosis, hepatitis, hepatic fibrosis or cirrhosis
+- AST and ALT < 2.5 x ULN (< 5 x ULN in patients with known liver metastases)
+Personal history of hepatitis or other liver diseases
+End-stage liver disease unrelated to tumor
+Visceral (e.g. lung, liver) metastases
+History of liver disease as defined with liver function tests (LFTs) above those in the inclusion
+Have a history of liver or renal dysfunction
+Alanine transaminase (ALT) =< 3 x ULN (=< 5 x ULN acceptable for pancreatic subjects with known liver metastasis only)
+Have a primary liver tumor
+The presence of liver lesion(s) (as defined in a.) with AFP ? 400 ng/mL.
+Criteria 2, More than one third of the liver is estimated to be involved with metastases
+AST and ALT ? 3.0 x ULN, independently of the presence of liver metastases.
+Severe liver disease (e.g. cirrhosis, non-alcoholic steatohepatitis, sclerosing cholangitis)
+Adequate liver function as demonstrated by:Total bilirubin of ?1.5 mg/dL or ?2.0 mg/dL for subjects with liver metastasis, Alanine aminotransferase ?3 x upper limit of normal (ULN) or ?5 x ULN if liver metastasis is present, Alkaline phosphatase ?3 x ULN or ?5 x ULN if bone or liver metastasis is present