Efficacy Evaluation of TheraSphere to Treat Inoperable Liver Cancer With Blockage of the Portal Vein
Condition: Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: TheraSphere®; Sorafenib
Intervention description: Intrahepatic treatment of advanced hepatocellular carcinoma; Standard of care therapy for treatment of advanced hepatocellular carcinoma
Intervention MeSH terms: Sorafenib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: hepatocellular carcinoma; portal vein thrombosis

Summary:

      This is a two-arm, open-label, prospective, multi-center, randomized, active-controlled
      clinical trial to assess efficacy and safety of TheraSphere in comparison to standard of care
      therapy (sorafenib) in the treatment of participants with inoperable liver cancer and
      blockage of the portal vein.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants over 18 years of age, regardless of race or gender

          -  Advanced unresectable hepatocellular carcinoma with branch portal vein thrombosis
             (confirmed by non-invasive criteria European Association for the Study of the Liver
             [EASL]/American Association for the Study of Liver Diseases [AASLD], mandatory by
             histology in non-cirrhotic participants); can be naive or recurrent HCC after curative
             treatment ( >6 months before randomization)

          -  Unilobar disease

          -  Child Pugh A

          -  Tumor volume ≤70% of liver volume (determined by visual estimation)

          -  At least one uni-dimensional HCC target lesion assessable by computed tomography (CT)
             or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid
             Tumor (RECIST) version 1.1

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

          -  Platelets ≥ 50*10^3/microliter (µL)

          -  White blood cell (WBC) ≥1.5*10^3/microliter (µL)

          -  Aspartate transaminase (AST)/ alanine aminotransferase (ALT) ≤5 times upper limit of
             normal

          -  Creatinine ≤2.0 mg/deciliter (dL)

          -  Life expectancy >3 months

          -  Signed informed consent

        Exclusion Criteria:

          -  Confirmed extra hepatic metastases. Participants with indeterminate hepatic hilar
             lymph nodes up to 2.5 centimeters (cm) in greatest dimension, or with indeterminate
             lung nodules (single lesion between 1-1.5 cm, or multiple smaller lesions with a total
             diameter of ≤2 cm) may be included if metastatic disease is deemed unlikely

          -  Known contraindication to standard-of-care sorafenib including allergic reaction, pill
             swallowing difficulty, uncontrolled hypertension or history of cardiac disease,
             significant GI bleed within 30 days, and renal failure including dialysis

          -  Evidence of hepatic vein invasion or caval thrombosis

          -  Evidence of chronic obstructive pulmonary disease

          -  Indication for any possible curative treatment after multidisciplinary assessment
             (surgery, ablation, transplantation)

          -  Previous treatment with sorafenib for more than 4 weeks during the previous 2 months;
             prior sorafenib-related toxicity

          -  Initiation of anti-tumor therapy including chemotherapy or investigational drug
             treatment within 30 days before beginning study

          -  Prior transarterial chemoembolization (TACE) <6 months prior to screening phase in
             case of participants progressing from an intermediate to an advanced stage due to
             occurrence of PVT

          -  On a transplant list

          -  History of organ allograft

          -  Contraindications to angiography or selective visceral catheterization

          -  History of severe allergy or intolerance to contrast agents, narcotics, sedatives, or
             atropine that cannot be managed medically

          -  Prior external beam radiation therapy to the liver

          -  Evidence of continuing adverse effect of prior therapy

          -  Active gastrointestinal (GI) bleeding and any bleeding diathesis or coagulopathy that
             is not correctable by usual therapy or hemostatic agents

          -  Evidence of any disease or condition that would place the participant at undue risk
             and preclude safe use of TheraSphere treatment

          -  Females of child-bearing potential must have a negative serum test

          -  No participation in concurrent clinical trials