A Phase II Randomized, Double-blind, Placebo-controlled Study of Sorafenib or Placebo in Combination With Transarterial Chemoembolization (TACE) Performed With DC Bead and Doxorubicin for Intermediate Stage Hepatocellular Carcinoma (HCC).
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Bayer
- Enrollment
- 307
- Locations
- 6
- Primary Endpoint
- Time to Progression (TTP) - Independent Radiological Review (Primary Analysis)
Study Overview
Brief Summary
This study will look at whether our drug (sorafenib) in combination with chemotherapy delivered directly into your tumor using beads (DC Bead) will slow the progression of the disease. The beads used with the chemotherapy will slowly release the chemotherapy reducing the adverse effects that normally occur with chemotherapy.
Detailed Description
Safety issues will be reported in Adverse Event section. In addition to the secondary outcome measures, Biomarkers and Patient Report Outcome will also be analyzed as other variables.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Unresectable, multinodular asymptomatic tumor without vascular invasion or extrahepatic spread
- •Confirmed Diagnosis of HCC:
- •Cirrhotic subjects: Clinical diagnosis by American Association for the Study of Liver Diseases (AASLD) criteria
- •HCC can be defined in cirrhotic subjects by one imaging technique (Computed tomography [CT] scan, Magnetic resonance imaging [MRI], or second generation contrast ultrasound) showing a nodule larger than 2 cm with contrast uptake in the arterial phase and washout in venous or late phases or two imaging techniques showing this radiological behavior for nodules of 1-2 cm in diameter.
- •Cytohistological confirmation is required for subjects who do not fulfill these eligibility criteria.
- •Non-cirrhotic subjects:
- •For subjects without cirrhosis, histological or cytological confirmation is mandatory
- •Documentation of original biopsy for diagnosis is acceptable
- •Child Pugh class A without ascites
- •Adequate bone marrow, liver and renal function as assessed by central lab by means of the following laboratory requirements from samples within 7 days prior to randomization:
Exclusion Criteria
- •Patients on a liver transplantation list or with advanced liver disease as defined below:
- •Child Pugh B and C
- •Active gastrointestinal bleeding
- •Encephalopathy
- •Lesions having previously been treated with local therapy such as resection of HCC, radiofrequency ablation (RFA), percutaneous ethanol injection (PEI) or cryoablation can not be selected as the target lesions.
Arms & Interventions
Sorafenib (Nexavar, BAY43-9006) + TACE
Sorafenib was to be orally administered as 2 x 200 mg tablets bid (twice daily). Patients were then also treated with Transarterial Chemoembolization (TACE) performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of sorafenib, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)
Intervention: Sorafenib (Nexavar, BAY43-9006) (Drug)
Placebo + TACE
Placebo was to be orally administered as 2 tablets bid (twice daily). Patients were then also treated with TACE performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of placebo, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Time to Progression (TTP) - Independent Radiological Review (Primary Analysis)
Time Frame: From randomization of the first participant until 28 months later (cut-off date)
TTP is defined as the time (days) from randomization to radiological confirmed disease progression. Participants without progression at the time of analysis were censored at their last date of tumor evaluation.
Secondary Outcomes
- Overall Survival (OS)(From randomization of the first participant until 28 months later (cut-off date))
- Tumor Response - Independent Radiological Review(From randomization of the first participant until 28 months later (cut-off date))
- Time to Untreatable Progression (TTUP)(From randomization of the first participant until 28 months later (cut-off date))
- Time to Vascular Invasion/Extrahepatic Spread (TTVI/ES)(From randomization of the first participant until 28 months later (cut-off date))
- Tumor Response - Investigator Assessment(From randomization of the first participant until 28 months later (cut-off date))