Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase III Multi-Centre Open-Label Randomized Controlled Trial of Selective Internal Radiation Therapy (SIRT) Versus Sorafenib in Locally Advanced Hepatocellular Carcinoma (SIRveNIB)
Brief Summary: The primary objective of this study is to assess the efficacy of SIRT as compared with Sorafenib in patients with locally advanced liver cancer in terms of overall survival (OS).

The Study null hypothesis is, there is no difference in overall survival between patients receiving SIRT and those receiving Sorafenib therapy.


Options:
A: 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
B: 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.
C: 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
D: Inclusion Criteria:

* Obesity: BM +/- 95% for age general good health

Answer: B