Liposomal Doxorubicin Plus Gemcitabine Versus Oxaliplatin Plus Fluorouracil/Leucovorin for Hepatocellular Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to determine that Liposomal Doxorubicin(LD) plus Gemcitabine(GEM) is superior to Oxaliplatin（OXA） Plus Fluorouracil/Leucovorin(FOLFOX4) in prolonging progression-free survival（PFS） in patients with Advanced Hepatocellular Carcinoma.

Official Title
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Liposomal Doxorubicin(LD) Plus Gemcitabine Versus Oxaliplatin Plus Fluorouracil/Leucovorin(FOLFOX4) As Palliative Chemotherapy in Patients With Advanced Hepatocellular Carcinoma(HCC)

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Liposomal Doxorubicin+Gemcitabine
* Drug: FOLFOX4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible patients were age 18 to 75 years; The patients had histologically, cytologically,or clinically diagnosed unresectable HCC;and were ineligible for local invasive treatment. Clinically diagnosed patients had to have: (1) evidence of HBV or HCV with hepatic cirrhosis; (2) a-fetoprotein levels 400g/L; and (3) morphologic evidence of hypervascular liver tumor. Patients had to have at least one measurable lesion according to RECIST (version 1.0; ≥2 cm on computed tomography [CT]; 1 cm on spiral CT or magnetic resonance imaging). Lesions that had undergone previous interventional or local therapy were not considered measurable lesions. ECOG score≤2; life expectancy 3 months; Barcelona Clinic liver cancer (BCLC) stage B or C disease; Child-Pugh stage A or B disease; Adequate organ and marrow function, with neutrophil count≥1.5X10e9/L, platelet count≥75×10e9/L, AST or ALT﹤2.5×upper limit of normal (ULN), total bilirubin <1.5×ULN, international normalized ratio <1.5;normal baseline left ventricular ejection fraction_lower limit of normal for the institution. Patients with AST and ALT< 5 ×ULN could be recruited if total bilirubin was in the normal range. Patients had to provide signed informed consent to participate. Exclusion Criteria: documented allergy to platinum compounds or other study drugs; any previous OXA or DOX treatment, except adjuvant treatment ﹥12 months before random assignment; Previous liver transplantation; concomitant use of any other anticancer therapy, including interferon alfa and herbal medicine approved by the local authority to be used as anticancer medicine (except palliative radiotherapy to a nontarget lesion); CNS metastasis; Other serious illness or medical condition.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Liposomal Doxorubicin+Gemcitabine<br>Gemcitabine 1000mg/m2,d1,8;Liposomal Doxorubicin 30mg/m2,d1.q4w | Drug: Liposomal Doxorubicin+Gemcitabine<br>* Gemcitabine 1000mg/m2,d1,8,iv; Liposomal Doxorubicin 30mg/m2,d1,iv.q4w of each 28 day cycle. 6 of Cycles: until progression or unacceptable toxicity develops or Progressive Disease.<br>* Other names: Liposomal Doxorubicin plus Gemcitabine;|
| Active Comparator: FOLFOX4<br>Oxaliplatin 85 mg/m2 intravenously on day 1; Leucovorin 200 mg/m2 IV(in vein) from hour 0 to 2 on days 1 and 2; and Fluorouracil 400 mg/m2 IV bolus at hour 2, then 600mg/m2 over 22 hours on days 1 and 2, once every 2 weeks | Drug: FOLFOX4<br>* Oxaliplatin 85 mg/m2 intravenously on day 1; Leucovorin 200 mg/m2 IV(in vein) from hour 0 to 2 on days 1 and 2; and Fluorouracil 400 mg/m2 IV bolus at hour 2, then 600mg/m2 over 22 hours on days 1 and 2, once every 2 weeks until progression or unacceptable toxicity develops or Progressive Disease.<br>* Other names: Oxaliplatin plus Fluorouracil/Leucovorin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free-Survival |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate |  | 3 months | 
| Overall survival |  | 6 months and 12 months | 
| Disease control rate |  | 3 months | 
| Time-to-Progression |  | 3 months |