Hepatocellular Carcinoma
Conditions
Keywords
liver cancer, first-line, tumor thrombus, vascular invasion
Brief summary
To evaluate and compare the efficacy and safety of sorafenib versus trans-arterial chemoembolization plus external beam radiation therapy in patients with hepatocellular carcinoma invading major intrahepatic vessels
Detailed description
Current practice guidelines recommend only sorafenib for patients with hepatocellular carcinoma invading major intrahepatic vessels. However, recent data from observational studies suggest that the combination of transarterial chemoembolization and external beam radiotherapy would be as effective as sorafenib.
Interventions
RADIATIONTACE+External beam RT
Trans-arterial chemoembolization (TACE) every 6 weeks + external beam radiation therapy starting within 3 weeks after first TACE
DRUGSorafenib
Sorafenib 800 mg/day orally
Sponsors
Asan Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>19 years * Child-Pugh class A liver function * Performance status: Eastern Cooperative Oncology Group (ECOG) score 0 or 1 * Hepatocellular carcinoma (HCC) confirmed by dynamic CT or MRI, or by biopsy * HCC invasion of first or second branch portal vein or hepatic vein or inferior vena cava * Reserved unilateral portal blood flow at least in partial * HCC size larger than 1 cm and less than 50% of total liver volume * No confirmed extrahepatic metastasis * Adequate hematopoietic function Hemoglobin ≥ 8.5 g/dL Absolute neutrophil count ≥ 750/mm3 Platelet count ≥ 30,000/mm3 * Creatinine \< 1.5mg/dL * No plan for pregnancy or breast feeding. Active contraception. * Willing to give informed consent
Exclusion criteria
* Prior history to or exposure of transarterial chemoembolization, external beam radiation to liver, or sorafenib * Complete obstruction of hepatic outflow * Confirmed extrahepatic metastasis of HCC * HCC occupying more than 50% of liver volume * Uncontrolled ascites of hepatic encephalopathy * Prior liver transplantation * Positive for human immunodeficiency virus (HIV) * Active gastric or duodenal ulcer * Other uncontrolled comorbidities or malignancy * Inability to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) rate | at 12 weeks after randomization | Progression is defined as progressive disease (PD) by independent radiologic review according to RECIST criteria (version 1.1), termination of the assigned treatment, or death from any cause, assessed by Kaplan-Meier analysis and log-rank test for treatment comparisons with the intention-to-treat principle. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Radiologic response rate | at 12 and 24 weeks after randomization | Radiologic response rate by independent radiologic review according to RECIST criteria (version 1.1), , assessed by Chi-square test or Fisher's exact test, as appropriate. |
| treatment-crossover rate | at 12 and 24 weeks after randomization | Crossover of treatment is permitted after confirming the disease progression during the initially assigned treatment, assessed by Kaplan-Meier analysis and log-rank test for treatment comparisons. |
| Progression-free survival (PFS) rate | at 24 weeks and up to 4 years after randomization | Progression is defined as progressive disease (PD) by independent radiologic review according to RECIST criteria (version 1.1), termination of the assigned treatment, or death from any cause, assessed by Kaplan-Meier analysis and log-rank test for treatment comparisons. |
| Overall patient survival rate | up to 4 years after randomization | The median overall patient survival rate assessed by Kaplan-Meier analysis and log-rank test for treatment comparisons. |
| Exploratory analysis for overall patient survival rate | up to 4 years after randomization | By using Cox proportional hazards model to evaluate the interaction between important baseline characteristics and the effect of treatments on overall survival. |
| time to progression | up to 4 years after randomization | The median time to progression assessed by Kaplan-Meier analysis and log-rank test for treatment comparisons. |
Countries
South Korea
Outcome results
None listed