Comparing Efficacy of Sorafenib Versus Sorafenib in Combination With Low-dose FP in Patients With Advanced HCC

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of sorafenib in combination with low dose cisplatin /fluorouracil hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma.

Detailed Description
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Sorafenib with Low-dose FP Group Sorafenib will be administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid) for 28 days. Cisplatin at the dose of 20mg/m2 will be administered at day 1 and day8, and fluorouracil at the dose of 330mg/m2 will be administered continuously at day1-day5, and day8-day12 via the implanted catheter system. Sorafenib Group Sorafenib will be administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid) for 28 days. The treatment regimen will be continued until radiographic or symptomatic progression, the development of unacceptable toxicity.

Official Title
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Randomized Controlled Trial Comparing Efficacy of Sorafenib Versus Sorafenib In Combination With Low Dose Cisplatin /Fluorouracil Hepatic Arterial InfUSion Chemotherapy in Patients With Advanced Hepatocellular Carcinoma

Conditions
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Advanced Hepatocellular Carcinoma, Carcinoma, Carcinoma, Hepatocellular, Liver Neoplasms, Neoplasms

Intervention / Treatment
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* Drug: Sorafenib with Low-dose FP
* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 20 Years and older. Life expectancy of at least 12 weeks at the pre-treatment evaluation. Advanced hepatocellular carcinoma with histological evidence on a biopsy specimen, or typical findings by dynamic CT or CT during hepatic arteriography/arterioportography. Not suitable for resection or local ablation therapy or transcatheter arterial chemoembolization. ECOG Performance status of 0 or 1. Cirrhotic status of Child-Pugh score ≤ 7. Adequate bone marrow, liver and renal function, as assessed by the following laboratory requirements: Hemoglobin ≥8.5 g/dl Granulocytes≥1500/μL Platelet count ≥50,000 /μL PT-INR ≤ 2.3 Total serum bilirubin ≤ 2 mg/dl AST(SGOT) and ALT(SGPT) ≤ 6 × upper limit of normal Serum creatinine ≤ 1.5 × upper limit of normal Amylase ≤ 2 × upper limit of normal Written Informed Consent must be obtained. Exclusion Criteria: Previous malignancy (except for cervical carcinoma in situ, adequate treated basal cell carcinoma, or superficial bladder tumors [Ta, Tis and T1], early gastric cancer, or other malignancies curatively treated > 3 years prior to entry Renal failure Any heart disease as follows Congestive heart failure defined as NYHA class III or IV Active coronary artery disease or ischemic heart disease such as cardiac infarction within 6 months prior to screening Serious cardiac arrhythmia Serious hypertension Active clinically serious infections except for HBV and HCV Active chicken pox. Auditory disorder. Known history of HIV infection. Known metastatic or meningeal tumors. Extrahepatic tumor spread which affects patient's prognosis History of seizure disorder. Clinically significant gastrointestinal bleeding within 4 weeks prior to study entry. Embolization or infarction such as transient ischemic disease, deep vein thrombosis, pulmonary embolization. Any history of treatment as follows: Treatment with the agent which induces CYP3A4 Surgical procedure within 4 weeks prior to start of study drug History of organ allograft Patients unable to swallow oral medications. Gastrointestinal disease that may affect to the absorption of drug or pharmacokinetics. Medication that may affect to the absorption of drug or pharmacokinetics. Any disease or disorder that may affect the evaluation of study drug. Entry to the other clinical trial within 4 weeks prior to entry to this study. Pregnant or breast-feeding patients. Known allergy to the investigational agent or any agent given in association with this trial. Substance abuse, medical, psychological or social conditions that, in the judgment of the investigator, is likely to interfere with the patient's participation in the study or evaluation of the stuy results. Any condition that is unstable or could jeopardize the safety of the patient and its compliance in the study, in the investigator's judgment.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sorafenib with Low-dose FP<br> | Drug: Sorafenib with Low-dose FP<br>* Sorafenib will be administered orally at a dose of 400 mg bid for 28 days in a cycle. Cisplatin at the dose of 20 mg/m2 will be administered at day 1 and day8, and fluorouracil at the dose of 330 mg/m2 will be administered continuously at day 1-day 5, and day8-day12 via the implanted catheter system. A cycle is defined as 28 days.<br>* Other names: Low-dose FP;|
| Active Comparator: Sorafenib<br> | Drug: Sorafenib<br>* Sorafenib will be administered orally at a dose of 400 mg bid for 28 days in each cycle.A cycle is defined as 28 days.<br>* Other names: Nexavar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | Overall survival is defined as the time from randomization to death due to any cause | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression |  | TTP is defined as the time from randomization to radiological progression. | 
| Progression Free Survival |  | PFS is defined as the time from randomization to radiological progression or death due to any cause | 
| Change of tumor marker |  | Every 4-6 weeks | 
| Biomarker predicting the efficacy |  | Pre and after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sorafenib, Hepatic intraarterial infusion chemotherapy, HAIC, Low dose FP, cisplatin, fluorouracil