Cholestatic disorders or unresolved veno-occlusive disease of the liver.
Liver function tests (including ALT, AST, and total bilirubin), outside of the range of local laboratory normal at Screening
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 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
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 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).
Tumor involvement > 50% of the liver
Cirrhotic liver disease from any cause
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
Greater than 50% tumor burden in the liver by imaging.
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.
Serologically positive for HIV; serologically positive for Hepatitis B or Hepatitis C with evidence of liver dysfunction or documented liver cirrhosis
No prior local, liver-directed therapy; prior surgical resection of oligometastatic liver disease is allowed
History of cirrhotic liver disease
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
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
Isolated liver sclerosis or pulmonary fibrosis, without active LCH.
-  Confirmed diagnosis of HCC > 10 mm with a characteristic 4-phase CT or dynamic\n             contrast enhanced MRI finding showing intense arterial uptake followed by \washout\ of\n             contrast in the venous-delayed phases per American Association for the Study of Liver\n             Disease (AASLD) criteria.\n\n          -  Patients between ages 20 and 80\n\n          -  Patients with single or multiple (2-4 nodules) HCC who are unsuitable or unwilling for\n             surgical resection or RFA. The largest tumor nodule should be less than 10 cm in the\n             largest diameter. The total volume of tumor cannot exceed 50% of liver; or patients\n             with liver metastatic gastrointestinal cancer, including neuroendocrine tumor\n\n          -  Patients are candidates for TAE or Transarterial ChemoEmbolization (TACE). No tumor\n             invasion to portal vein or thrombosis in portal vein.\n\n          -  ECOG score 0-1 with no known cardiac, pulmonary or renal dysfunction\n\n          -  Child-Pugh score group A or B7 liver functional score\n\n          -  Prior local therapies such as surgical resection, radiofrequency ablation, or alcohol\n             injection are allowed as long as tumor progresses from the prior treatment and the\n             patients are still candidates for TAE. All prior therapy must be at least 4 weeks\n             prior to enrollment and free from treatment-related toxicity.\n\n          -  No TAE/TACE in the past\n\n          -  Patients have normal organ function: ANC ? 1000 /µL, Hemoglobin ? 9 gm/dL, Platelets ?\n             50,000 /µL, Creatinine ? 2 mg/dL, AST and ALT < 5 X upper normal limit of the current\n             institution; bilirubin ? 3.0 mg/dL, PT prolongation no more than 4 sec above upper\n             limit of normal.\n\n        For the expansion cohort of neuroendocrine tumor or metastatic gastrointestinal cancer\n\n          -  Unresectable, locally advanced or metastatic, well differentiated (low or intermediate\n             grade), neuroendocrine tumors (NET).\n\n          -  Liver metastatic gastrointestinal cancer.
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
Histologically confirmed metastatic uveal melanoma in the liver; patients must have at least one measurable liver metastasis that is ? 10 mm in longest diameter by spiral computed tomography (CT) scan or magnetic resonance imaging (MRI); the total volume of the tumors must be less than 50% of the liver volume
Has greater than 75% liver parenchyma replacement by tumor
High screening liver function tests
Presence of parenchymal liver metastases on imaging
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).
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
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
Patients with either a confirmed diagnosis of (1) metastatic colorectal cancer in liver based on histopathology of either a prior resection of primary lesion or a biopsied liver metastatic lesion; (2) advanced HCC (BCLC-stage C) with a characteristic 3 or 4-phase CT or dynamic contrast enhanced MRI finding showing arterial uptake followed by \washout\ of contrast in the venous-delayed phases per American Association for the Study of Liver Disease (AASLD) criteria; (3) metastatic gastric cancer; (4) metastatic NSCLC without EGFR or ALK mutation.
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
Patients with diffuse/multifocal liver involvement are eligible
History of cirrhotic liver disease
Patients with greater than 50% liver tumor burden
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
Patients should agree to serial liver metastases biopsy pre-treatment, post-radioembolization, and post-combination immunotherapy
Liver involvement by > 50% with metastatic disease determined by the investigator
Subjects with diagnosed active liver disease or with elevation of liver enzymes/bilirubin.
Patients must have liver metastasis
Patients are excluded if they have liver tumor volume > 50%
If elevated liver function tests develop at the time of initial presentation or develop during workup and are the result of mechanical obstruction of the biliary drainage by tumor compression or invasion, a biliary drain may be placed; if drainage allows the liver function tests to come within inclusion criteria, the patient may be enrolled
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
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)
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
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
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
Liver tumors must not be estimated to invade approximately more than one-third of the liver.
Major liver vascular invasion
Patients with parenchymal 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 function tests > 3 x upper limit of normal
Adequate liver function with serum AST, ALT and bilirubin within the normal range at the time of crenolanib commencement
Bilirubin < 1.5 x normal except in cases where abnormal liver function tests (LFTS) are due to involvement with T-NHL
Known or active hepatitis B or C with abnormal liver function tests
Liver function test (LFTs) =< 2 x upper limit of normal
Metastatic disease is allowed if investigator feels liver directed therapy could offer palliative benefit (i.e., minimal extrahepatic tumor burden)
Laboratory evaluations (kidney and liver) outside normal limits and of potential clinical significance in the opinion of the investigator
All patients must have at least one metastatic or primary lesion within the lung or liver located in an anatomical location amenable to SBRT treatment with 50 Gy in 4 fractions, or if not, with either a lung, liver, or adrenal lesion treatable to 60 Gy in 10 fractions
Patients will be staged according to the Barcelona Clinic Liver Cancer (BCLC) criteria
Tumor involving > 50% of the liver
Expected ablation volume > 30% of total liver volume or removal of 3 hepatic segments
Prior radiation to liver in form of total body or involved field
Patients with a history of or active liver failure
Liver enzymes < 3 fold the upper limit of normal
Bulky disease patients - tumors encompassing >50% of the liver volume and / or inferior vena cava invasion
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
Diagnosis of unresectable intrahepatic HCC. The histopathology confirmation criterion may be waived in patients with a radiographically identifiable liver mass, known laboratory or clinical risk factors for cancer or elevated tumor markers such as alphafetoprotein (AFP)^21 and clinical findings. Guidelines from the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) describe in detail the approach and algorithm for diagnosing HCC.
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)
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).
Liver function tests documented within the screening period and on day -1 of treatment period:
Chronic inflammatory liver condition.
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).
Liver function tests > 3 x upper limit of normal
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
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 A: Predominant intrahepatic burden (> 75%) of disease (i.e. patients with widespread extrahepatic disease to organs other than the liver will not be included)
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
Patients with liver metastases who do not meet the eligibility parameters may only be enrolled at the discretion of the principal investigator (PI)
Decompensated liver disease in which pegylated interferon is contraindicated
History or other evidence of decompensated liver disease
History or other evidence of decompensated liver disease
Tumor replacement <50% of total liver volume
Ongoing liver injury
Abnormal liver function test results
Liver function tests (LFTs) greater than twice the upper limit of normal
Patients with known liver disease (alcoholic, drug/toxin induced, genetic, or autoimmune);
Tumor replacement > 70% of total liver volume based on visual estimation by investigator OR tumor replacement >50% of total liver volume in the presence of albumin <3 mg/dL
Prior yttrium-90 microsphere treatment to the liver
Cancer that has spread to the liver or brain
Patients with liver metastasis may not be included if AST and/or ALT >5 xULN
Has extensive metastatic tumor burden in the liver with serum albumin < 3.0 g/dL
Patients must have liver metastases.
Suspected pulmonary and/or liver metastases (greater >= 10 mm in largest axis)
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
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.
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
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
Known liver disease, autoimmune hepatitis, or sclerosing cholangitis.
Patients with elevated liver function tests including jaundiced patients (due to tumor) can be selectively operated on without resolution of jaundice preoperatively according to the judgment of the operating surgeon
Tumor replacement > 70% of total liver volume based on visual estimation by the investigator OR tumor replacement > 50% of total liver volume in the presence of albumin < 3 mg/dL
Barcelona Clinical Liver Cancer Classification (BCLC) B or C
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.
Liver metastases
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
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
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).
Histologically confirmed metastatic uveal melanoma in the liver; patients must have at least one untreated, or progressed liver metastasis that is >= 10 mm in longest diameter by spiral computed tomography (CT) scan or magnetic resonance imaging (MRI); the total volume of the tumors must be less than 50% of the liver volume
A solitary liver metastasis that is amenable to surgical removal for potential cure
Known hepatitis B virus carriers who have liver function tests within the accepted limits are eligible
Liver function tests (LFT's) =< 5 x upper limit of institutional normal (ULN)
LIVER (ONLY APPLIES TO PATIENTS WITH METASTATIC LIVER LESIONS NOT PREVIOUSLY TREATED WITH RT):
Chronic or active hepatitis B or hepatitis C; if questions about liver health, discuss with principal investigator (PI) and strongly consider liver biopsy
Acute liver disease or previously diagnosed liver tumor (benign or malignant)
Subjects with unresolved veno-occlusive disease of the liver.
Preserved liver function
Presence of advanced liver disease.
Ongoing liver injury
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:
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
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 surgery for the IHC; (liver resection is not allowed)
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
Ongoing liver injury
Have had anti-cancer treatment following liver resection that exceeded a duration of 6 months.
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
Tumor volume ? 70% of liver volume (determined by visual estimation)
Confirmed diagnosis of HCC by histological examination or by non-invasive criteria according to European Association for the Study of the Liver (EASL) or American Association for the Study of Liver Disease (AASLD) guidelines (Part 1, 2 and 3).
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
History of cirrhotic liver disease
Active liver disease with elevated transaminases > 2 x ULN
Patients with > 3 liver metastases at time of enrollment
Patients must have one focus of metastatic disease in the liver that is amenable to SBRT in the opinion of radiation oncology
Prior liver directed radiation
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.
Patients with known liver metastases
Presence of less than 70% liver involvement by cancer
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
Patients with advanced malignant hepatic tumors (liver metastases that replace more than 30% of the liver parenchyma)
Greater than 50% tumor burden in the liver by imaging
Prior selective internal radiation to the liver
Liver function tests with values > 3 x ULN
Liver metastases
History of veno-occlusive disease of the liver
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)
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
Recent cholecystectomy, liver resection, or biliary surgery within 12 months.
Significant liver metastatic disease interfering with safe/effective percutaneous transhepatic biliary drainage (PTBD).
Known or suspected gynecologic or other abdominal malignancy (such as colorectal, liver, pancreatic, kidney and stomach) for which laparotomy is planned
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
Documented liver disease with marked elevation of transaminases >3 x ULN or,
Total bilirubin < 2.0 mg/dl; unless hepatic dysfunction is a manifestation of presumed cGVHD; for patients with abnormal liver function tests (LFTs) as the sole manifestation of active cGVHD, documented cGVHD 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 active hepatic cGVHD, and a liver biopsy will not be mandated in this situation
Aspartate aminotransferase (AST) < 5 x upper limit of normal (ULN), unless hepatic dysfunction is a manifestation of presumed cGVHD; for patients with abnormal LFTs as the sole manifestation of active cGVHD, documented cGVHD 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 active hepatic cGVHD, and a liver biopsy will not be mandated in this situation
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
No significant synthetic dysfunction of the liver; if there is a question of such, a liver biopsy should be performed for further assessment
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
The patient’s planned cancer management is radiation to the liver with or without chemotherapy
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
Women with active liver disease, abnormal uterine bleeding, or prior diagnosis of endometrial hyperplasia
Laboratory evaluations (kidney and liver) outside normal limits and of potential clinical significance in the opinion of the investigator
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
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)
Referral from an internist, oncologist, or surgeon for liver tumor ablation consultation
Patients in liver failure as judged by the patient’s physician
Liver metastases on most recent prior M.D. Anderson CT examination.
Patient is referred for 90Y SIRT radioembolization of liver tumor(s)
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
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)
Patients with confined liver disease or stable limited extrahepatic disease
Liver function tests (LFTS) =< 1.5 x upper limit of normal (ULN)
Patients must have liver-dominant or liver-only metastatic disease from any primary histology; patients with primary hepatocellular or biliary cancer are also eligible
Must have been listed on the regional OPTN/UNOS liver transplant wait list with HCC-exception Model for End Stage Liver Disease (MELD) points prior to enrollment in this trial OR \r\n* Site principal investigator (PI) or designated site co-investigator determines whether patient is likely to meet all criteria for being listed on the regional OPTN/UNOS liver transplant waitlist with HCC-exception MELD points, but has not yet been listed with UNOS UNet\r\n* Investigator has completed and signed the Declaration of Intent to List source document declaring that the patient will likely meet all wait list criteria\r\n* Participants listed with the intent to undergo either deceased donor transplant or live donor adult liver transplantation (LDALT) are eligible for this trial
No treatment affecting the status of liver between MRI/MRE and post-imaging biopsy
Diagnosis of malignant liver tumor; (pathological diagnosis of malignancy or at least one liver lesion seen on imaging that is suspicious for malignancy)
Prior systemic treatment or radiation therapy is allowed for patients with resectable liver metastases\r\n* The last dose of chemotherapy or radiation must have been administered at least 4 weeks prior to liver surgery\r\n* The last dose of bevacizumab must have been administered at least 6 weeks prior to liver resection
History of liver disease as defined with liver function tests (LFTs) above those in the inclusion
Have a primary liver tumor
Criteria 2, More than one third of the liver is estimated to be involved with metastases
Adequate bone marrow and organ function, as defined by the protocol
Adequate organ and bone marrow function:
Participant has adequate bone marrow and organ function as defined by the following laboratory values:
Patients must have adequate organ and bone marrow function within 14 days prior to registration, as defined below:
Adequate bone marrow and organ function
Adequate organ function defined as: Bone Marrow:
Subject has adequate bone marrow and organ function as shown by:
Patients must have adequate organ and bone marrow function within 14 days prior to registration, as defined by: leukocytes >= 2,000/mcL
Subjects with adequate organ and bone marrow function as defined below:
Adequate organ and bone marrow function
Patients must have adequate organ and bone marrow function =< 14 days prior to registration, as defined below:
Patients must have adequate bone marrow and organ function.
Adequate organ and bone marrow function defined by routine testing
Adequate bone marrow and organ function defined by laboratory values
Adequate bone marrow and organ function
Adequate organ and bone marrow function
Adequate bone marrow and organ function as assessed by the laboratory tests performed within 7 days before of treatment initiation.
Patients must have adequate organ and bone marrow function =< 14 days prior to registration, as defined below (Note: blood transfusion or growth factors is not permitted within 14 days of registration):
Adequate bone marrow and organ function
Adequate organ and bone marrow function determined within 14 days prior to enrollment defined as:
Patient has adequate bone marrow and organ function
Patient has adequate bone marrow and organ function
Patients must have adequate organ and bone marrow function
Patients must have adequate organ and bone marrow function within 14 days prior to registration, as defined below:
Life expectancy ? 12 weeks. 7. ECOG PS of 0 or 1 8. Adequate organ and bone marrow function 9. Ability to undergo during screening a tumor biopsy that is adequate for biomarker analysis.
Adequate organ and bone marrow function within the 21 days prior to randomization defined by:
Adequate bone marrow and organ function
Adequate bone marrow, organ function, cardiac and laboratory parameters
Adequate bone marrow, organ function, cardiac and laboratory parameters
Have adequate organ and bone marrow function.
Acceptable bone marrow and organ function at screening;
Adequate bone marrow function and organ function
Patient has adequate bone marrow and organ function.
Adequate bone morrow and organ function
Adequate bone marrow and organ function
Patient has adequate bone marrow and organ function.
Adequate organ or bone marrow function
Adequate bone marrow and organ function
Patient has adequate bone marrow and organ function
Adequate organ and bone marrow function
Adequate organ and bone marrow function as assessed by laboratory tests
Adequate bone marrow and organ function
Adequate bone marrow and organ function
Adequate bone marrow and organ function as determined by the consenting/enrolling investigator
Organ Function Requirements Patients without bone marrow metastases must have an ANC > 500/?l and platelet count >50,000/?l.
Patients must have adequate organ and bone marrow function 10 days prior to registration, as defined below:
Adequate bone marrow and organ function as defined as:
Adequate organ function for patients receiving crizotinib therapy as defined by the following criteria: Bone marrow function
Adequate organ and bone marrow function
Adequate organ and bone marrow function
Normal organ and marrow function:
Patients must have normal or near normal organ function as defined by their treating institutions BMT program clinical practice guidelines.
Patients must have normal organ and marrow function as defined at the discretion of the treating physician and principal investigator (PI)
PRE-SCREENING: Must have normal organ function with liver function tests (LFTs) < 2.5 x upper limit of normal (ULN)
Normal organ and bone marrow function defined as:
Normal bone marrow and organ function as defined below:
Adequate normal organ and marrow function as defined below (must be done within 30 days prior to enrolment):
Patients must have normal organ function as defined below:
Patients must have normal organ function as defined below:
Normal organ and bone marrow function as defined by:
Acceptable organ and marrow function during the Screening Period as defined by the\n             protocol.
Patients must have normal organ and bone marrow function measured within 28 days of randomisation,
Have organ and marrow function at the screening and pre-dose visits as defined by:
Patients must have normal organ and marrow function as defined below:
Patients must have normal organ and marrow function documented within 7 days of study enrollment as defined below:
Patients must have normal marrow function as defined below:
Patient must have normal bone marrow and organ function as defined below
Patients must have normal organ and marrow function as defined below:
Normal organ and bone marrow
ECOG performance status ? 1 Patients must have normal organ and marrow function as defined below:
Subjects must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment;
Patients must have normal organ and marrow function as defined below:
Patients must have normal organ and marrow function as defined below:
Must have normal organ and marrow function reported within 14 days prior to randomization
The subject has poor organ and marrow function as defined in the protocol.
Subject must have normal organ and marrow function as defined below:
Patients must have normal organ and marrow function as defined below:
Patients must have normal organ and marrow function
Normal organ function tests including Creatinine
Normal organ function tests including Bilirubin
Normal organ and marrow function.
Normal organ and marrow function
Normal organ and marrow function within limits as defined below:
Patients must have normal marrow function as defined:
Subjects must have normal organ and marrow function as defined below:
Subjects must have normal organ and marrow function as defined below:
Adequate bone marrow reserve as evidenced by:
Bone marrow reserve which, in the clinical judgment of the Principal Investigator, is not adequate for participation in this trial.
Patients must have adequate bone marrow reserve as evidenced by:
Poor bone marrow reserve.
Adequate bone marrow reserve
Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
Adequate organ function within 14 days of study registration including:\r\n* Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) >= 1.0 x 10^9/L
Adequate bone marrow reserve as demonstrated by :
Subjects with recent history of inadequate bone marrow reserve as demonstrated by previous transfusions except for acute blood loss (e.g. surgery) in the month prior to screening
Recent history of inadequate bone marrow reserve as demonstrated by the following:
Adequate organ function and bone marrow reserve as indicated by the following laboratory assessments performed at screening.
Inadequate organ function or bone marrow reserve as demonstrated by the following laboratory values:
Inadequate bone marrow reserve or organ function.
Patients must have adequate bone marrow reserve as evidenced by:
Adequate bone marrow reserve and organ function as demonstrated by complete blood count, and biochemistry in blood and urine at baseline
Poor bone marrow reserve.
Adequate bone marrow reserve (neutrophils > 1000/mm3 and platelets > 80000/ mm3)
Adequate bone marrow reserve without transfusions defined as:
Poor bone marrow reserve.
Have adequate organ reserve as determined by laboratory test results obtained within 2 weeks prior to Study Day 1 as indicated below:
Inadequate bone marrow reserve or organ function
Inadequate marrow reserve assessed by hematologic laboratory parameters
Inadequate bone marrow reserve or organ function
Inadequate bone marrow reserve
Inadequate bone marrow reserve or organ function
Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
Adequate bone marrow reserve as evidenced by ANC > 1.0x10^9/L;Platelet > 50x10^9/L
Adequate bone marrow reserve
Two weeks must have elapsed since completion of prior chemotherapy, minor surgery, radiotherapy (provided that no more than 25% of bone marrow reserve has been irradiated)
Two weeks must have elapsed since completion of prior chemotherapy, minor surgery, radiotherapy (provided that no more than 25% of bone marrow reserve has been irradiated)
Adequate bone marrow reserve, hepatic and renal function, as demonstrated by:
Patients who have had radiation to the pelvis or other bone marrow-bearing sites will be considered on a case by case basis and may be excluded if the bone marrow reserve is not considered adequate (> 25% of bone marrow)
Has adequate bone marrow reserve, hepatic and renal function, as demonstrated by:
Has adequate bone marrow reserve as evidenced by:
Subject must have adequate hematologic reserve
Inadequate bone marrow reserve
Patient with glioblastoma must have adequate bone marrow and immune reserve, as documented by:
Have adequate bone marrow reserve and organ function at screening as follows:
Adequate bone marrow reserve as demonstrated by
The patient has adequate bone marrow reserve: • Absolute neutrophil count (ANC) > 0.5 × 10^9/L
Patients must have adequate physiologic reserve as evidenced by:
Patient has adequate bone marrow reserve, as evidenced by:
Patients who have had radiation to the pelvis or other bone marrow-bearing sites will be considered on a case by case basis and may be excluded if the bone marrow reserve is not considered adequate (> 25% of bone marrow irradiated)
Adequate bone marrow reserve as defined per protocol;
Have adequate bone marrow reserve defined as:
Patients who have undergone prior stem cell transplant will not be excluded from study entry as long as adequate marrow reserve is demonstrated (refer to hematologic parameters)
Subjects with recent history of inadequate bone marrow reserve as demonstrated by previous transfusions except for acute blood loss (e.g. surgery) in the month prior to screening
Adequate bone marrow reserve
Adequate hepatic reserve
Adequate bone marrow reserve and renal and hepatic function within 28 days before the first dose of study drug on the basis of the defined laboratory parameters.
Adequate liver function, including:
Adequate liver function must be demonstrated, defined as:
Adequate liver function must be demonstrated, defined as:
Acceptable liver function:
Acceptable liver function:
Adequate liver function
Acceptable liver function:
Adequate liver function:
Hepatic: Adequate liver function is defined as:
Adequate liver function
Acceptable liver function, as specified below:
Adequate liver function defined by:
Acceptable liver function at Screening,
Have acceptable liver function defined as:
Acceptable liver function:
Subjects must have adequate liver function as defined by:
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
Adequate liver function as demonstrated by:
Acceptable liver function:
Adequate liver function, defined as:
Liver function:
Adequate liver function
Participant must have adequate liver function as demonstrated by:
Subject has adequate liver function defined as:
Participants must have adequate liver function, defined as:
Adequate liver function:
Acceptable liver function within 7 days of day 1 of therapy defined as:
Participant must have adequate liver function as demonstrated by:
Adequate liver function:
Adequate liver function as evidenced by:
Adequate Liver Function:
Subjects must have adequate liver function as defined by:
Acceptable liver function
Adequate liver function, defined as:
Adequate liver function at Cycle 1 Day 1 pre-dosing defined as:
Acceptable liver function
Acceptable liver function
Adequate liver function
ENROLLMENT: Adequate liver function, defined as: total bilirubin =< 2 mg/dl
Acceptable liver function
Liver function < 3 x normal
Subjects must have adequate liver function, including all of the following:
Liver function defined as:
Adequate liver function:
Adequate liver function
Adequate liver function:
Participants with Hepatitis B or C are eligible on the condition that they have adequate liver function as defined by Inclusion Criterion 9.
Adequate liver function
Acceptable liver function
Adequate liver function, defined as:
Subject must have adequate liver function as demonstrated by:
Adequate liver function
Adequate liver function defined as:
Acceptable liver function defined as:
Adequate liver function, defined as both of the following:
Adequate liver function
Adequate liver function, defined as:
Adequate liver function
Adequate liver function, defined as:
Adequate liver function, defined as:
Acceptable liver function
Acceptable liver function:
Patients must have adequate liver function
Subjects must have adequate liver function
Adequate liver function, defined as:
Adequate liver function
Adequate liver function within 72 hours of enrollment, defined as:
Acceptable liver function
Adequate liver function as demonstrated by
Adequate liver function (as defined in the study protocol)
Liver function:
Adequate liver function, defined as:
Normal liver function based on Liver Function Tests (Total Bilirubin and AST <1.5 X Upper Limit of Normal).
Adequate liver function, as indicated by bilirubin =< 1.5 x ULN
Have adequate liver function defined as:
Adequate liver function:
Liver: Subjects must have adequate liver function
Patients must have adequate liver function as defined by AST or ALT <10x normal
Adequate liver function:
Adequate liver function defined as:
Adequate function of liver:
Adequate liver function:
Adequate bone marrow function:
Insufficient bone marrow function
Adequate bone marrow function
Adequate bone marrow function:
Adequate bone marrow function:
Hematologic function: Adequate bone marrow function is defined as:
Adequate bone marrow function
Adequate bone marrow function
Adequate bone marrow function defined by:
Adequate Bone Marrow Function.
Adequate bone marrow function.
Have acceptable bone marrow function defined as:
Bone marrow function:
Adequate bone marrow function:
Adequate bone marrow function at screening
Subject has adequate bone marrow function defined as:
Participants must have adequate bone marrow function, defined as:
Adequate bone marrow function:
Assessed by the investigator to have adequate bone marrow function to receive lymphodepleting conditioning chemotherapy
Adequate bone marrow function within 7 days and defined as:
Adequate bone marrow function as evidenced by:
Adequate bone marrow function
Adequate bone marrow reservation:
Assessed by the investigator to have adequate bone marrow function to receive lymphodepleting conditioning chemotherapy
Bone marrow function:
Adequate marrow function
Adequate bone marrow function Haemoglobin (Hb) ?100g/L and White Cell Count (WCC) ? 4.0 x 109/L and platelets ?100 x 109/L
Adequate bone marrow function as evidenced by:
Adequate bone marrow function:
Adequate Bone Marrow Function:
Subjects must have adequate Bone Marrow function defined as: For patients without bone marrow involvement:
Adequate bone marrow function, defined as:
ENROLLMENT: Evidence of adequate bone marrow function (defined by absolute neutrophil count >= 750), unless patient has documented tumor metastasis to the bone marrow or other condition that results in cytopenia without abnormal marrow function.
ENROLLMENT: Evidence of adequate bone marrow function (defined by platelets >= 50,000), unless patient has documented tumor metastasis to the bone marrow or other condition that results in cytopenia without abnormal marrow function.
The subject will have adequate bone marrow function
Patients must have adequate heart, kidney, liver and bone marrow function. Patients who have bone marrow disease must still have adequate bone marrow function to enter the study.
Patients who have bone marrow disease must still have adequate bone marrow function to enter the study.
Patient has adequate bone marrow function
Adequate bone marrow function:
Adequate bone marrow function
Adequate bone marrow function:
Adequate bone marrow function
Bone marrow function:
Adequate bone marrow function.
Adequate bone marrow function, defined as:
Adequate bone marrow function
Have adequate bone marrow and hepatic function.
Adequate bone marrow function
Participant has adequate bone marrow function, evidenced by the following:
Adequate bone marrow function: Haemoglobin (Hb) ?100g/L and White Cell Count (WCC) ? 4.0 x 109/L and platelets ?100 x 109/L.
Subject has adequate bone marrow function.
Patient has adequate bone marrow function defined as:
Patients must have adequate bone marrow function, defined as
Subject must have adequate bone marrow function at Screening
Subjects must have adequate bone marrow function as evidenced by:
Adequate bone marrow function
The patient has adequate bone marrow function, evidenced by the following:
Adequate bone marrow function documented by:
Assessed by the Investigator to have adequate bone marrow function to receive lymphodepleting chemotherapy
Adequate bone marrow function for participants with solid tumors without known bone marrow involvement
Adequate bone marrow function for participants with known bone marrow metastatic disease
Adequate bone marrow function, defined as:
Adequate bone marrow and hematological function.
Adequate bone marrow function
Adequate bone marrow function:
Adequate bone marrow function.
Adequate bone marrow function
Adequate bone marrow function
Adequate bone marrow function
Adequate bone marrow function, defined as:
Adequate bone marrow function
Adequate bone marrow function
Adequate bone and marrow function as defined below:
Adequate bone marrow function
Adequate bone marrow function as defined as:
Adequate bone marrow function
Adequate bone marrow function
Participants with solid tumors (with the exception of neuroblastoma) must have adequate bone marrow function in Part 1.
Adequate bone marrow function, defined as:
Adequate bone marrow function.
Adequate bone marrow function:
Adequate bone marrow function as evidenced by:
Adequate bone marrow function:
Adequate function of bone marrow:
Adequate bone marrow function: