Study of Regorafenib After Sorafenib in Patients With Hepatocellular Carcinoma (RESORCE)

Inclusion Criteria:

• 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
• Barcelona Clinic Liver Cancer stage Category B or C that cannot benefit from treatments of established efficacy with higher priority such as resection, liver transplantation, local ablation, chemoembolization or systemic sorafenib.
• Failure to prior treatment with sorafenib (defined as documented radiological progression according to the radiology charter). Randomization needs to be performed within 8 weeks after the last treatment with sorafenib.
• Tolerability of prior treatment with sorafenib defined as not less than 20 days at a minimum daily dose of 400 mg QD within the last 28 days prior to withdrawal.
• Liver function status Child-Pugh Class A. Child Pugh status should be calculated based on clinical findings and laboratory results during the screening period.
• Local or loco-regional therapy (e.g. surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed >/= 4 weeks before first dose of study medication.
• Eastern Cooperative Oncology Group Performance Status of 0 or 1.
• Adequate bone marrow, liver and renal function as assessed by the following laboratory tests conducted within 7 days before randomization.
• Glomerular filtration rate >/= 30 ml/min/1.73 m2 according to the Modification of diet in renal disease abbreviated formula.
• At least one naïve (not previously treated by locoregional therapy such as surgery, radiation therapy, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation) uni-dimensional measurable lesion
• Life expectancy of at least 3 months.
• Women of childbearing potential and men must agree to use adequate contraception .

Exclusion Criteria:

• Sorafenib treatment within 2 weeks of randomization.
• Prior systemic treatment for HCC, except sorafenib.
• Permanent discontinuation of prior sorafenib therapy due to sorafenib related toxicity.
• Known history or symptomatic metastatic brain or meningeal tumors (head CT or MRI at screening to confirm the absence of central nervous system [CNS] disease if patient has symptoms suggestive or consistent with CNS disease).
• Uncontrolled hypertension (systolic blood pressure [BP] > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management).
• Uncontrolled ascites (defined as not easily controlled with diuretic or paracentesis treatment).
• Ongoing infection > Grade 2 according to NCI-CTCAE (National Cancer Institute - Common Terminology Criteria for Adverse Events) v. 4.0. Hepatitis B and Hepatitis C are allowed if no active replication is present.
• Clinically significant bleeding NCI-CTCAE version 4.0 Grade 3 or higher within 30 days before randomization.
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study medication.
• Patients unable to swallow oral medications.
• Interstitial lung disease with ongoing signs and symptoms at the time of screening.