| Eligibility |
Inclusion Criteria:
1. Male or female, age = 18 years and =70 years.
2. Histological or cytological confirmation of HCC (hepatocellular carcinoma) or
non-invasive diagnosis of HCC as per American Association for the Study of Liver
Diseases criteria in patients with a confirmed diagnosis of cirrhosis.
3. Barcelona Clinic Liver Cancer stage Category B or C that cannot benefit from
treatments of locoregional therapy, or provided that progression has been documented
after these therapies.
4. Patients should have failed or been intolerant of at least one prior systemic therapy
regimen which could include systemic chemotherapy (such as oxaliplatin, arsenious
acid) and/or sorafenib.
5. At least one uni-dimensional measurable lesion according to RECIST (RECIST version
1.1), and modified RECIST for HCC (mRECIST):a. HCC lesions should have at least one
accurate repeated dimension as 1 cm or more ); b. extrahepatic lesions: a lymph node
must be 1.5 cm or more in short axis, and Non-lymph node lesions must be at least 1 cm
in longest diameter. Tumor lesions situated in a previously irradiated area, or in an
area subjected to other loco-regional therapy, may be considered measurable if there
has been demonstrated progression in the lesion.
6. Liver function status Child-Pugh Classification with score = 7 points. Child Pugh
status should be calculated based on clinical findings and laboratory results during
the screening period.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8. Laboratory criteria are as follows (laboratory results within 7 days prior to first
dose, and without receiving any supportive treatment for the following parameters
within 2 weeks from the last dose prior to study entry):
1. Complete blood count: white blood cell count = 3.0×109/L; absolute neutrophil
count (ANC) =1.5×109/L ;hemoglobin (Hb) =85g/L ; platelets >=60×109/L
2. Biochemistry test: total bilirubin?1.5×ULN; alanine aminotransferase(ALT)
,aspartate aminotransferase(AST)?5×ULN ; plasma albumin= 28 g/L; serum
creatinine(cr)?1.5×ULN; serum amylase?1.5×ULN;
3. Coagulation test: International Normalized Ratio (INR) < 1.5; activated partial
thromboplastin time (APTT) < 1.5×ULN
4. Thyroid function test: thyroid stimulating hormone (TSH) < 10mIU/L;
9. Life expectancy of at least 12 weeks.
10. All patients must have given signed, informed consent prior to registration on study.
Exclusion Criteria:
1. Any target treatment like sorafenib within 2 weeks prior to first dose of study drug;
With the exception of target treatment, any anti-cancer systemic treatment (including
chemotherapy, immunotherapy, radiotherapy, and anti-cancer Chinese traditional
medicine, et al) or locoregional therapy (including but not limited to surgery,
radiofrequency ablation or transarterial chemoembolization ) within 4 weeks prior to
first dose of study drug; any supportive treatment for haematology (including
transfusion, blood products, or drugs that stimulate blood cells growth like G-CSF, et
al) within 2 weeks prior to first dose of study drug.
2. Known Cholangiocarcinoma or Fibrolamellar Hepatocellular Carcinoma; Known history of,
or ongoing second primary cancer, except: adequately treated basal cell or squamous
cell skin cancer, curatively treated in-situ cancer of the cervix, unless received
curative treatment and with documented evidence of no recurrence during the past five
years;
3. Known metastatic brain or meningeal tumors
4. Patients with uncontrolled or significant cardiovascular disease, including:
1. Grade II or higher Congestive heart failure, unstable angina pectoris, myocardial
infarction (NYHA Classification) within 6 months prior to study entry; or
arrhythmia requiring treatment, or Left Ventricular Ejection Fraction (LVEF) <
50% during screening stage.
2. Primary cardiomyopathy (dilated cardiomyopathy, hypertrophic cardiomyocyte,
arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy,
et,al).
3. History of significant QT interval prolongation, or Corrected QT Interval
QTc=450ms(male), QTc=470ms(female)at screening.
4. Symptomatic coronary heart disease requiring treatment.
5. Uncontrolled hypertension (> 140/90 mmHg) with single medication.
5. History of active bleeding within 6 months or esophageal varices bleeding led by
portal hypertension within 2 months prior to screening ; or patients receiving
anticoagulation therapy; or patients with evidence of GI bleeding potential.
6. Uncontrolled ascites or pleural effusion (defined as not easily controlled with
diuretic or paracentesis treatment).
7. History of transjugular intrahepatic portosystemic shunts (TIPSS).
8. History of abdominal fistula, gastrointestinal perforation or abdominal abscess within
28 days prior to screening.
9. History of deep vein thrombosis or pulmonary embolism.
10. History of interstitial lung disease(ILD), or with ongoing signs and symptoms at the
time of screening.
11. History of hypothyroidism; or patients receiving substitutional treatment with thyroid
hormone.
12. With any ongoing toxicities (>CTCAE grade 1) caused by previous cancer therapy.
13. Patients with factors that could affect oral medication (such as dysphagia, chronic
diarrhea, intestinal obstruction etc), or undergone gastrectomy.
14. History of liver transplantation, or patients in preparation of liver transplantation.
15. 6 weeks or less from the last major surgery that involved general anaesthesia, or 2
weeks or less from the last minor surgery prior to screening (excluding placement of
vascular access ) .
16. Proteinuria positive(=1g/24h).
17. Patients with active or unable to control infections including human immunodeficiency
virus (HIV), or other serious infectious diseases.
18. Patients with untreated active hepatitis B virus (HBV) (HBsAg positive and HBV DNA =
2000 IU/mL) . But patients with controlled(treated) HBV fulfilling the following
criteria can be eligible for the study: HBV DNA< 2000 IU/mL , or patients on anti-HBV
suppression with HBV DNA< 2000 IU/mL before study enrollment.
19. Patients with untreated active hepatitis C virus.
20. Any mental or cognitive disorder, that would impair the ability to understand the
informed consent document, or limit compliance with study requirements/treatment.
21. Any previous treatment with aurora kinase inhibitors.
22. Candidates with drug abuse.
23. Women of childbearing potential not willing to use and utilize an adequate method of
contraception (such as intrauterine device, contraceptive and condom) throughout
treatment and for at least 12 weeks after the last dose; pregnant or breastfeeding
women; the result of urine pregnancy test was positive at screening; Man participants
not willing to use and utilize an adequate method of contraception throughout
treatment.
24. Any other condition which is inappropriate for the study according to investigators'
judgment.
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