This trial is active, not recruiting.

Condition carcinoma, hepatocellular
Treatments regorafenib (bay73-4506), placebo
Phase phase 3
Sponsor Bayer
Start date May 2013
End date February 2016
Trial size 573 participants
Trial identifier NCT01774344, 15982, 2012-003649-14


This clinical study evaluates the efficacy and safety of regorafenib in patients with advanced liver cancer who have progressed on sorafenib treatment.

Approximately 560 patients who meet the entry criteria will be randomly assigned in a 2:1 ratio to regorafenib or placebo (1/3 chance to receive placebo).

Primary endpoint of the study is overall survival.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
160 mg orally (p.o.) every day (qd) for 3 weeks of every 4 week cycle (i.e. 3 weeks on, 1 week off) plus BSC (Best Supportive Care)
regorafenib (bay73-4506)
Regorafenib, 40 mg tablets
(Placebo Comparator)
4 matching placebo tablets for 3 weeks of every 4 week cycle (i.e. 3 weeks on, 1 week off) plus BSC
Placebo tablets matching in appearance

Primary Outcomes

Overall survival
time frame: Approximately 33 months.

Secondary Outcomes

Time to progression
time frame: Approximately 33 months.
Progression free survival (PFS)
time frame: Approximately 33 months.
Objective tumor response
time frame: Approximately 33 months.
Disease control
time frame: Approximately 33 months.

Eligibility Criteria

Male or female participants at least 18 years old.

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, 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 10 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 of intrahepatic tumor lesions (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. Note: patients who received sole intrahepatic intraarterial chemotherapy, without lipiodol or embolizing agents are not eligible. - 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 study equation. - At least one uni-dimensional measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to RECIST (RECIST version 1.1), and modified RECIST for HCC. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, may be considered measurable if there has been demonstrated progression in the 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 is allowed if no active replication is present. Hepatitis C is allowed if no antiviral treatment is required. - 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.

Additional Information

Official title A Randomized, Double Blind, Placebo Controlled, Multicenter Phase III Study of Regorafenib in Patients With Hepatocellular Carcinoma (HCC) After Sorafenib
Description Regorafenib BAY73-4506
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Bayer.
Location data was received from the National Cancer Institute and was last updated in August 2016.