Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Prospective Randomized Open-labeled Trial Comparing RADIOEMBOLIZATION With Yttrium 90 Microspheres and Sorafenib in Patients With Advanced Hepatocellular Carcinoma
Brief Summary: The purpose of this study is to determine whether RADIOEMBOLIZATION with 90 Yttrium microspheres is more effective on overall survival in advanced Hepatocellular carcinoma (HCC) with or without portal venous obstruction and no extrahepatic extension than sorafenib which is now the standard treatment of advanced HCC.


Options:
A: Inclusion Criteria:

* Histological or cytological diagnosis or meet the AASLD criteria for diagnosis of HCC and at least one uni-dimensional lesion measurable according to RECIST criteria by CT-scan or MRI
* Adult over 18 years old and estimated life expectancy over 3 months
* Patient with advanced HCC according to BCLC staging system (stage C) with or without portal vein thrombosis, not eligible for surgical resection, liver transplantation nor radiofrequency ablation OR patient with progression or recurrence of HCC after surgical or locoregional treatment not eligible for surgical resection, liver transplantation nor radiofrequency ablation OR patients in whom chemoembolisation has failed after two courses (patients who have received only one course of chemoembolisation are eligible if the failure of the first round shows that a second round will have no more impact; patients who have received more than two courses of chemoembolisation are still eligible if the arterial network is perfectly normal on a CT scan in the arterial phase). Failure is defined as the absence of an objective response after two courses of treatment in the treated nodule (objective response according to modified RECIST criteria and/or EASL criteria).
* ECOG performance status under or equals 1
* Adequate haematological function: Hb over or equals 9g/100mL, absolute neutrophil count over or equals 1 500/mm3, platelet count over or equals 50 000/mm3
* Adequate renal function; serum creatinine under 150μmol/L
* Bilirubin under or equals 50 µmol/L, AST or ALT uner or equals 5 x ULN, INR under or equals 1.5
* Liver cirrhosis Child Pugh A - B7
* written informed consent

Exclusion Criteria:

* Another primary tumour, with the exception of conventional basal cell carcinoma or superficial bladder neoplasia
* Extrahepatic metastasis
* Advanced HCC previously treated
* Advanced liver disease with Child-Pugh score over 7 or active gastrointestinal bleeding or encephalopathy or ascites refractory to diuretic therapy Women who are pregnant or breast feeding
* Allergy to contrast media
* Contraindication to hepatic artery catheterisation, such as severe peripheral vascular disease precluding catheterisation
* Psychiatric or other disorder likely to impact on informed consent
* Patient unable and/or unwilling to comply with treatment and study instructions
* Patient unable to swallow oral medications
B: Inclusion Criteria:

1. Diagnosis of HCC confirmed by histology or non-invasive criteria (EASL/AASLD)
2. Intermediate stage (BCLC-B) HCC: patients with a large or multinodular HCC (single HCC \> 5 cm or multiple HCC defined as \> 3 nodules \> 3 cm), a Child Pugh class A or B7 and no cancer related symptoms (PS=0-1).
3. Advanced stage (BCLC-C) HCC: patients with hepatic vascular involvement (at any tumor number and diameter), a Child Pugh class A or B7, no cancer related symptoms (PS=0-1) and absence of extra-hepatic tumor spread.
4. Cancer-related symptoms within the ECOG 0-1 score
5. Liver function within Child B-7 class
6. Platelets \> 50.000/µL
7. WBC \> 1500/µL
8. AST/ALT \< 5 times the upper limit of normal (U/L)
9. Creatinine \< 2.0 mg /dL
10. No indication for any possible curative treatment after multidisciplinary assessment (resection, ablation, transplantation)
11. Signed informed consent

Exclusion Criteria:

1. Child-Pugh class higher than B-7 at entry
2. ECOG performance score ≥ 2 at entry
3. Tumor volume ≥ 50% of liver volume
4. Extrahepatic tumor spread
5. Pulmonary insufficiency
6. Life expectancy of less than 3 months due to HCC or less than 6 months due to any other disease
7. Previous chemoembolization procedure (TACE)
8. Evidence on 99mTc-MAA scan of vascular shunts that can not be corrected by angiographic coil embolization
9. Evidence on 99mTc-MAA scan of lung shunting, with a potential absorbed dose of radiation to the lungs \> 30 Gy
C: Inclusion Criteria:

* Disease must be locally advanced as defined by BCLC (B) intermediate stage or BCLC (C) advanced stage without extra-hepatic disease (only with branch portal vein thrombosis).
* Willing, able and mentally competent to provide written informed consent prior to any testing undertaken for this study protocol, including screening tests and evaluations that are not considered to be part of the subject's routine care.
* Aged 18 years/older (either gender).
* Unequivocal diagnosis of HCC.
* HCC not amenable to surgical resection or immediate liver transplantation, or cannot be optimally treated with local ablative techniques such as RFA, consistent with the practice of the clinical trial centre.
* Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with spiral CT scan or MRI.
* ECOG performance status 0-1.
* Child-Pugh A-B (up to 7 points)
* Adequate haematological, renal and hepatic function as follows:
* Leukocytes ≥ 2,500/μL
* Platelets ≥ 80,000/μL
* Haemoglobin \> 9.5g/dL
* Total bilirubin \< 2.0mg/dL
* INR ≤ 2.0
* ALP ≤ 5 x institutional ULN
* AST and ALT ≤ 5 x institutional ULN
* Albumin ≥ 2.5g/dL
* Creatinine ≤ 2.0mg/dL
* Life expectancy of at least 3 months without any active treatment.
* Suitable for protocol treatment as determined by clinical assessment undertaken by the Investigator.
* Female patients must be either postmenopausal or, if premenopausal, must have a negative pregnancy test and agree to use 2 forms of contraception if sexually active during their study participation.
* Male patients must be surgically sterile, or if sexually active and having a pre-menopausal female partner then must be using an acceptable form of contraception.

Exclusion Criteria:

* Have had more than 2 administrations of hepatic artery directed therapy.
* Subjects who have had hepatic artery directed therapy done \< 4 weeks prior to study entry.
* Have had systemic chemotherapy for HCC except for prior adjuvant or neoadjuvant therapy given more than 6 months from enrolment.
* have had prior treatment with Sorafenib or VEGF inhibitors.
* Prior hepatic radiation therapy for HCC or other malignancy.
* Currently receiving any other investigational agents for the treatment of their cancer.
* Has intractable clinical ascites (in spite of optimal diuretic treatment) or any other clinical signs of liver failure, on physical examination.
* Complete main portal vein thrombosis.
* Any metastatic disease (local-regional lymph nodes measuring less than 2 cm in greatest diameter or lung nodules measuring less than 1 cm are not contraindications as per Investigator discretion).
* Any other concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for at least 5 years.
* Presence of clinical signs of CNS metastases due to their poor prognosis and because progressive neurologic dysfunction would confound the evaluation of neurologic and other adverse events.
* Uncontrolled inter-current illness including, but not limited to, ongoing or active infection (except viral hepatitis), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Any of the following contraindications to angiography and selective visceral catheterization:
* Bleeding diathesis, not correctable by the standard forms of therapy.
* Severe peripheral vascular disease that would preclude arterial catheterization.
* Portal hypertension with hepato-fugal flow as documented on baseline spiral CT scan.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to SIR-Spheres or Sorafenib.
* Inability or unwillingness to understand or sign a written informed consent document.
* Female subjects who are pregnant or currently breastfeeding.
* Female subjects, unless postmenopausal or surgically sterile, unwillingness to practice effective contraception, as per Investigator discretion during the study. The rhythm method is not to be used as the sole method of contraception.
* Male subjects, unwillingness to practice effective contraception (per Investigator discretion) while taking part in this study, because the effect of the SIR-Spheres treatment on sperm or upon the development of an unborn child are unknown.
* Current enrolment in any other investigational therapeutic drug or device study.
D: DISEASE CHARACTERISTICS:

* Hepatocellular Carcinoma confined to the liver that is unresectable with surgery or unable to be treated with radiofrequency ablation diagnosed by biopsy or imaging criteria (CT/MRI)
* No segmental, lobar, or main portal vein thrombosis as evidenced by CT or MRI imaging

Inclusion Criteria

* Adults \> 18 years old of either gender
* Diagnosis of liver confined HCC confirmed by histology or American Association for the Study of Liver Diseases (AASLD) guidelines \[59,60\] \[appendix A\].
* Lesions \< 1 cm in diameter have a low likelihood of being malignant and should be followed. Lack of growth over 1-2 years suggests it is not HCC.
* AFP \>200 and radiological evidence (arterial hypervascularity) of lesion \> 2 cm does not require biopsy.
* Two imaging modalities (triphasic CT, MRI, ultrasound, angiography) demonstrating "arterial hypervascularity" in the background of cirrhosis does not require biopsy
* One imaging modality with a lesion with arterial hypervascularity with wash out in early or delayed venous phase, does not require a biopsy
* Atypical appearances on imaging requires a biopsy.
* Non-conclusive biopsy requires closer monitoring
* For non-cirrhotics (by biopsy or imaging findings), diagnosis of HCC requires biopsy
* Patients with \<50% liver involvement
* Measurable liver confined disease with bi-dimensional measurements, required within 4 weeks of screening. Lesions reported on imaging as "too small to characterize", abdominal lymph nodes \< 2.0 cm or ascites in the setting of cirrhosis are not considered metastatic disease unless cytology proven.
* No segmental, lobar or main portal vein thrombosis as evidence by cross sectional imaging
* Prior resection permitted, no prior systemic, ablative or infusion therapy permitted
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 \[appendix B\]
* Childs score of A or B \[appendix C\]
* Required lab parameters within 28 days of screening
* Serum bilirubin ≤ 2.0 mg/dl (unless segmental infusion can be performed
* AST and ALT ≤ 5 times upper limit of normal (ULN)
* Creatinine ≤ 1.5 times ULN
* Prothrombin time (PT)/ International normalized ratio (INR) ≤ 2.3 or PT ≤ 6 seconds above control. If subjects are being anticoagulated they can participate if proof of no coagulation abnormality existed prior to use of anticoagulants
* Negative serum or urine pregnancy test for females of child bearing potential
* Ability to understand and sign the informed consent; patient must have signed informed consent prior to registration on study
* Women of childbearing potential and sexually active males must use contraception while on study
* Lesions must be treatable angiographically by either radioembolization or chemoembolization.

Exclusion criteria

* Cardiac disease: Congestive heart failure \> class II New York Heart Association (NYHA). Patients must not have unstable angina (angina symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
* Patients with infiltrative HCC are not eligible.
* Patients with bulk disease (≥70% tumor replacement of liver) are not eligible.
* Patients with ≥50% tumor replacement of liver, with an albumin \< 3.0 g/dl are not eligible.
* Major surgery within 4 weeks prior to the screening visit
* Active clinically serious infection \> Common Toxicity Criteria for Adverse Events (CTCAE v 4.0) Grade 2
* Any condition (psychological, physical or use/abuse of substances) which, in the opinion of the principal investigator (PI) or a sub-investigator (sub-I), would possibly endanger the subject during their participation in the study, or allow for non-compliance with the investigational drug and treatment under study.
* Due to the experimental nature of the therapy and the unknown risk to a fetus, pregnant and/or lactating women are not eligible to participate in this study.
* In the opinion of the investigator, patient is not a candidate/lesion not amenable for RFA (e.g. lesion location, shape, abnormal coagulation parameters, multi-focality).

Answer: A