Informed Consent
Item
1. signed written informed consent must be obtained and documented according to international conference on harmonisation (ich) and local regulatory requirements
boolean
C0021430 (UMLS CUI [1])
Metastatic hepatocellular carcinoma | Unresectable hepatocellular carcinoma | Recurrent Hepatocellular Carcinoma
Item
2. histologically or cytologically confirmed hepatocellular carcinoma that is metastatic, unresectable, or recurrent
boolean
C0744869 (UMLS CUI [1])
C1112459 (UMLS CUI [2])
C0861876 (UMLS CUI [3])
Patients Inappropriate Excision Curative
Item
1. patients must not be candidates for curative resection
boolean
C0030705 (UMLS CUI [1,1])
C1548788 (UMLS CUI [1,2])
C0728940 (UMLS CUI [1,3])
C1276305 (UMLS CUI [1,4])
Recurrent disease | Status post Excision Quantity
Item
2. patients who have recurrent disease after having had one or more prior resections may be eligible, provided that they are not candidates for further curative resection
boolean
C0277556 (UMLS CUI [1])
C0231290 (UMLS CUI [2,1])
C0728940 (UMLS CUI [2,2])
C1265611 (UMLS CUI [2,3])
Exclusion | Recurrent Hepatocellular Carcinoma Following Transplantation of liver
Item
3. patients who have recurrent hepatocellular carcinoma following hepatic transplantation are excluded
boolean
C0680251 (UMLS CUI [1])
C0861876 (UMLS CUI [2,1])
C0332282 (UMLS CUI [2,2])
C0023911 (UMLS CUI [2,3])
Patients Appropriate Sorafenib
Item
3. patients must be candidates for sorafenib
boolean
C0030705 (UMLS CUI [1,1])
C1548787 (UMLS CUI [1,2])
C1516119 (UMLS CUI [1,3])
Cancer treatment Systemic Absent | Therapy Local-Regional allowed
Item
4. must have had no previous systemic anti-cancer treatment, though previous loco-regional therapy is allowed:
boolean
C0920425 (UMLS CUI [1,1])
C0205373 (UMLS CUI [1,2])
C0332197 (UMLS CUI [1,3])
C0087111 (UMLS CUI [2,1])
C1947913 (UMLS CUI [2,2])
C0683607 (UMLS CUI [2,3])
Transarterial embolization | Transarterial Chemoembolization | Percutaneous ethanol injection therapy | Radioembolisation | Radiofrequency ablation | Ablation
Item
a. prior treatment with any of the following is allowed: trans-arterial embolization, trans-arterial chemo-embolization, percutaneous ethanol injection, radio-embolization, radio-frequency ablation, or other ablation techniques
boolean
C3163695 (UMLS CUI [1])
C3539919 (UMLS CUI [2])
C1535909 (UMLS CUI [3])
C2985560 (UMLS CUI [4])
C0850292 (UMLS CUI [5])
C0547070 (UMLS CUI [6])
Child-Pugh Classification
Item
5. must be child-pugh class a
boolean
C2347612 (UMLS CUI [1])
Exclusion Criteria | ASCITES MASSIVE Uncontrolled | Hepatic Encephalopathy
Item
a. patients with uncontrolled massive ascites or presence of hepatic encephalopathy are excluded
boolean
C0680251 (UMLS CUI [1])
C0741241 (UMLS CUI [2,1])
C0205318 (UMLS CUI [2,2])
C0019151 (UMLS CUI [3])
Age
Item
6. ≥ 18 years of age
boolean
C0001779 (UMLS CUI [1])
Measurable Disease
Item
7. measurable disease as defined by response evaluation criteria in solid tumors (recist) 1.1
boolean
C1513041 (UMLS CUI [1])
ECOG performance status
Item
8. eastern cooperative oncology group (ecog) performance status of 0 or 1
boolean
C1520224 (UMLS CUI [1])
Females & males of reproductive potential Contraceptive methods
Item
9. male or female patients of child-producing potential must agree to use contraception or avoidance of pregnancy measures during the study and for 30 days after the last bbi608 or bbi503 dose
boolean
C4034483 (UMLS CUI [1,1])
C0700589 (UMLS CUI [1,2])
Childbearing Potential Serum pregnancy test negative
Item
10. females of childbearing potential must have a negative serum pregnancy test
boolean
C3831118 (UMLS CUI [1,1])
C0430061 (UMLS CUI [1,2])
Aspartate aminotransferase measurement | Alanine aminotransferase measurement
Item
11. aspartate aminotransferase (ast) and alanine transaminase (alt) < 5.0 x the upper limit of normal (uln)
boolean
C0201899 (UMLS CUI [1])
C0201836 (UMLS CUI [2])
Creatinine measurement, serum | Estimation of creatinine clearance by Cockcroft-Gault formula
Item
12. creatinine ≤ 1.5 x uln or creatinine clearance > 50 ml/min according to the cockcroft-gault estimation
boolean
C0201976 (UMLS CUI [1])
C2711451 (UMLS CUI [2])
Hemoglobin measurement
Item
13. hemoglobin ≥ 8.5 mg/dl
boolean
C0518015 (UMLS CUI [1])
Absolute neutrophil count
Item
14. absolute neutrophil count ≥ 1.5 x 10^9/l
boolean
C0948762 (UMLS CUI [1])
Platelet Count measurement
Item
15. platelets ≥ 60 x 10^9/l
boolean
C0032181 (UMLS CUI [1])
Life Expectancy
Item
16. life expectancy ≥ 3 months
boolean
C0023671 (UMLS CUI [1])
Sorafenib Prior Therapy
Item
1. previous treatment with sorafenib
boolean
C1516119 (UMLS CUI [1,1])
C1514463 (UMLS CUI [1,2])
Hypersensitivity Sorafenib | Hypersensitivity Sorafenib Component
Item
2. patients with known hypersensitivity to sorafenib or any other component of sorafenib
boolean
C0020517 (UMLS CUI [1,1])
C1516119 (UMLS CUI [1,2])
C0020517 (UMLS CUI [2,1])
C1516119 (UMLS CUI [2,2])
C1705248 (UMLS CUI [2,3])
Vascular Endothelial Growth Factor Inhibitor Systemic therapy | Cancer treatment Systemic | regorafenib | ramucirumab | pazopanib | brivanib
Item
3. previous systemic anti-vascular endothelial growth factor (vegf) or any prior systemic anti-cancer therapy, including prior treatment with systemic agents such as regorafenib, ramucirumab, pazopanib, or experimental agents such as brivanib
boolean
C4521299 (UMLS CUI [1,1])
C1515119 (UMLS CUI [1,2])
C0920425 (UMLS CUI [2,1])
C0205373 (UMLS CUI [2,2])
C2980094 (UMLS CUI [3])
C2742502 (UMLS CUI [4])
C1831796 (UMLS CUI [5])
C2700604 (UMLS CUI [6])
Operative Surgical Procedure Requirement General Anesthesia | Hospitalization Recovery
Item
4. have had a surgical procedure requiring general anesthesia or inpatient hospitalization for recovery less than 4 weeks prior to beginning protocol therapy
boolean
C0543467 (UMLS CUI [1,1])
C1514873 (UMLS CUI [1,2])
C0002915 (UMLS CUI [1,3])
C0019993 (UMLS CUI [2,1])
C2004454 (UMLS CUI [2,2])
Recurrent Hepatocellular Carcinoma Following Transplantation of liver
Item
a. patients who have recurrent hepatocellular carcinoma following liver transplantation are excluded, regardless of how long ago the transplantation occurred
boolean
C0861876 (UMLS CUI [1,1])
C0332282 (UMLS CUI [1,2])
C0023911 (UMLS CUI [1,3])
Therapeutic procedure Local-Regional Liver carcinoma | Therapeutic procedure Percutaneous | Therapeutic procedure Transarterial | Radiofrequency ablation
Item
5. have had a loco-regional procedure for the treatment of hepatocellular carcinoma (such as a percutaneous, trans-arterial, or radio-ablative procedure) less than 4 weeks prior to beginning protocol therapy. protocol therapy may begin a minimum of 4 weeks after such a procedure provided the following criteria are met:
boolean
C0087111 (UMLS CUI [1,1])
C1947913 (UMLS CUI [1,2])
C2239176 (UMLS CUI [1,3])
C0087111 (UMLS CUI [2,1])
C0522523 (UMLS CUI [2,2])
C0087111 (UMLS CUI [3,1])
C0522522 (UMLS CUI [3,2])
C0850292 (UMLS CUI [4])
Disease Progression
Item
1. there is progression of disease documented by recist 1.1
boolean
C0242656 (UMLS CUI [1])
Adverse events Resolved
Item
2. all adverse events from the procedure have resolved or have been deemed irreversible and the patient meets inclusion criteria
boolean
C0877248 (UMLS CUI [1,1])
C1514893 (UMLS CUI [1,2])
Metastatic malignant neoplasm to brain Symptomatic | Metastatic malignant neoplasm to brain Untreated | Metastatic Malignant Neoplasm to the Leptomeninges
Item
6. any known symptomatic or untreated brain metastases requiring increase of steroid dose within 2 weeks prior to starting on study. patients with treated brain metastases must be stable for 4 weeks after completion of that treatment. patients must have no clinical symptoms from brain metastases and must be either off steroids or on a stable dose of steroids for at least 2 weeks prior to protocol enrollment. patients with known leptomeningeal metastases are excluded, even if treated
boolean
C0220650 (UMLS CUI [1,1])
C0231220 (UMLS CUI [1,2])
C0220650 (UMLS CUI [2,1])
C0332155 (UMLS CUI [2,2])
C1704231 (UMLS CUI [3])
Pregnancy | Breast Feeding
Item
7. pregnant or breastfeeding
boolean
C0032961 (UMLS CUI [1])
C0006147 (UMLS CUI [2])
Gastrointestinal Diseases Impairing Drug absorption | Crohn Disease | Ulcerative Colitis | Gastrectomy Extensive | Small intestine excision Extensive
Item
8. significant gastrointestinal disorder(s), (e.g., crohn's disease, ulcerative colitis, extensive gastric and small intestine resection) such that, in the opinion of the treating investigator, absorption of oral medications may be impaired
boolean
C0017178 (UMLS CUI [1,1])
C0221099 (UMLS CUI [1,2])
C0678745 (UMLS CUI [1,3])
C0010346 (UMLS CUI [2])
C0009324 (UMLS CUI [3])
C0017118 (UMLS CUI [4,1])
C0205231 (UMLS CUI [4,2])
C0192601 (UMLS CUI [5,1])
C0205231 (UMLS CUI [5,2])
Lacking Able to swallow BBI608 Capsules | Lacking Able to swallow BBI503 Capsules | Lacking Able to swallow Sorafenib Capsules | Lacking Able to swallow BBI608 Tablets | Lacking Able to swallow BBI503 Tablets | Lacking Able to swallow Sorafenib Tablets
Item
9. unable or unwilling to swallow bbi608, bbi503, or sorafenib capsules or tablets
boolean
C0332268 (UMLS CUI [1,1])
C2712086 (UMLS CUI [1,2])
C3272772 (UMLS CUI [1,3])
C0006935 (UMLS CUI [1,4])
C0332268 (UMLS CUI [2,1])
C2712086 (UMLS CUI [2,2])
C3641863 (UMLS CUI [2,3])
C0006935 (UMLS CUI [2,4])
C0332268 (UMLS CUI [3,1])
C2712086 (UMLS CUI [3,2])
C1516119 (UMLS CUI [3,3])
C0006935 (UMLS CUI [3,4])
C0332268 (UMLS CUI [4,1])
C2712086 (UMLS CUI [4,2])
C3272772 (UMLS CUI [4,3])
C0039225 (UMLS CUI [4,4])
C0332268 (UMLS CUI [5,1])
C2712086 (UMLS CUI [5,2])
C3641863 (UMLS CUI [5,3])
C0039225 (UMLS CUI [5,4])
C0332268 (UMLS CUI [6,1])
C2712086 (UMLS CUI [6,2])
C1516119 (UMLS CUI [6,3])
C0039225 (UMLS CUI [6,4])
Comorbidity Uncontrolled | Communicable Disease | Wound, non-healed | Wound healed | Symptomatic congestive heart failure | Angina, Unstable | Cardiac Arrhythmia | Lung disease | Resting Dyspnea | Dyspnea Exertion Mild | Communicable Diseases Uncontrolled | Mental disorders Limiting Protocol Compliance | Social situation Limiting Protocol Compliance
Item
10. uncontrolled inter-current illness including, but not limited to: ongoing or active infection, clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), or uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements (e.g. no reliable transportation)
boolean
C0009488 (UMLS CUI [1,1])
C0205318 (UMLS CUI [1,2])
C0009450 (UMLS CUI [2])
C0750433 (UMLS CUI [3])
C0574776 (UMLS CUI [4])
C0742758 (UMLS CUI [5])
C0002965 (UMLS CUI [6])
C0003811 (UMLS CUI [7])
C0024115 (UMLS CUI [8])
C0743330 (UMLS CUI [9])
C0013404 (UMLS CUI [10,1])
C0031807 (UMLS CUI [10,2])
C2945599 (UMLS CUI [10,3])
C0009450 (UMLS CUI [11,1])
C0205318 (UMLS CUI [11,2])
C0004936 (UMLS CUI [12,1])
C0439801 (UMLS CUI [12,2])
C0525058 (UMLS CUI [12,3])
C0748872 (UMLS CUI [13,1])
C0439801 (UMLS CUI [13,2])
C0525058 (UMLS CUI [13,3])
Cancer Other Primary | Exception Skin carcinoma Resected Curative | Exception Curative treatment Carcinoma in situ of uterine cervix | Exception Solid Neoplasm Inactive
Item
11. subjects with a history of another primary cancer, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present that, in the opinion of the investigator, will not affect patient outcome in the setting of current hepatocellular carcinoma diagnosis
boolean
C1707251 (UMLS CUI [1,1])
C0205225 (UMLS CUI [1,2])
C1705847 (UMLS CUI [2,1])
C0699893 (UMLS CUI [2,2])
C1521996 (UMLS CUI [2,3])
C1276305 (UMLS CUI [2,4])
C1705847 (UMLS CUI [3,1])
C1273390 (UMLS CUI [3,2])
C0851140 (UMLS CUI [3,3])
C1705847 (UMLS CUI [4,1])
C0280100 (UMLS CUI [4,2])
C0544452 (UMLS CUI [4,3])
ECG abnormal | Prolonged QT interval | Prolonged QTc interval | Cardiomegaly | Bundle-Branch Block New | Signs Ischemia | Infarction New York Heart Association Classification | Cardiac Arrhythmia Marked | Wolff-Parkinson-White Syndrome | Atrioventricular dissociation Complete
Item
12. abnormal ecgs which are clinically significant such as qt prolongation (qtc > 480 msec), clinically significant cardiac enlargement or hypertrophy, new bundle branch block, or signs of active ischemia. patients with evidence of prior infarction who are new york heart association (nyha) functional classes ii, iii, or iv are excluded, as are patients with marked arrhythmias such as wolff parkinson white pattern or complete atrioventricular (av) dissociation
boolean
C0522055 (UMLS CUI [1])
C0151878 (UMLS CUI [2])
C1560305 (UMLS CUI [3])
C0018800 (UMLS CUI [4])
C0006384 (UMLS CUI [5,1])
C0205314 (UMLS CUI [5,2])
C0311392 (UMLS CUI [6,1])
C0022116 (UMLS CUI [6,2])
C0021308 (UMLS CUI [7,1])
C1275491 (UMLS CUI [7,2])
C0003811 (UMLS CUI [8,1])
C1706089 (UMLS CUI [8,2])
C0043202 (UMLS CUI [9])
C2882262 (UMLS CUI [10,1])
C0205197 (UMLS CUI [10,2])