Efficacy Evaluation of TheraSphere to Treat Inoperable Liver Cancer With Blockage of the Portal Vein

A Prospective Randomized Clinical Trial on 90Yttrium Trans-arterial Radio-Embolization (TheraSphere®) vs. Standard of Care (Sorafenib) for the Treatment of Advanced Hepatocellular Carcinoma (HCC) With Portal Vein Thrombosis (PVT)

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.

The objective of this Phase III, prospective randomized trial is to determine whether TheraSphere provides a meaningful benefit in survival in comparison with the standard of care (sorafenib) in participants with good hepatic function and advanced hepatocellular carcinoma (HCC) associated with portal vein thrombosis (PVT).

This is an open-label prospective, multi-center, randomized, controlled clinical trial that will evaluate the use of TheraSphere compared to standard-of-care sorafenib alone.

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