Oxaliplatin + 5-FluoroUracil/LeucoVorin (5-FU/LV) (FOLFOX4) Versus Doxorubicin as Palliative Chemotherapy in Advanced Hepatocellular Carcinoma Patients

Study Overview
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Brief Summary
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Primary: Overall Survival (OS) Secondary: Time to Tumor Progression (TTP) Response Rate (RR) Improvement of Quality of Life (QoL) Safety Secondary resection rate

Official Title
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Oxaliplatin(Eloxatin®) + 5-FU/LV (FOLFOX4) Compared With Single Agent Doxorubicin (Adriamycin®) as Palliative Chemotherapy in Advanced Hepatocellular Carcinoma Patients Ineligible for Curative Resection or Local Treatment

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Drug: Oxaliplatin + 5-Fluorouracil/Leucovorin
* Drug: Doxorubicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically, cytologically or clinically diagnosed (in patient with cirrhosis, Alpha-Fetoprotein(AFP)≥400μg/L and morphological evidence [contrast Computed Tomography(CT)/Magnetic Resonance Imaging(MRI)] of hypervascular liver tumor, elevated AFP level due to other reasons [germ cell carcinoma, progressive chronic hepatitis, pregnancy, etc] can be excluded) unresectable hepatocellular carcinoma, ineligible or if the patient does not consent to receive local invasive treatment (chemo-embolism, ablation, etc.). At least one measurable lesion (on CT: ≥2cm, on spiral CT or MRI ≥1cm) Have not received previous palliative systemic chemotherapy for metastatic disease. If the patient received previous systemic chemotherapy as adjuvant treatment, he must have been completed at least 12 months previously. Patients progress after previous local treatment and at the time of randomization is at least 4 weeks after the last interventional therapy (Hepatic Artery Infusion, Trans-Artery Embolization or Trans-Artery Chemo-Embolization) or at least 8 weeks after the last radiotherapy/ablation/ Percutaneous Ethanol Injection to the target lesion. Karnofsky Performance Score≥70, Barcelona of Cancer Liver Category stage B/C Patients must have adequate organ and marrow function: Neutrophilus≥1.5X10^9/L Platelets≥75X10^9/L Asparagine AminoTransferase,Alanine AminoTransferase<2.5 Upper Normal Limit(UNL) Total Bilirubin<1.5 UNL International Normalized Ratio<1.5 Child stage A or B Normal base line Left Ventricular Ejection Fraction (LVEF result must be above or equal to the lower limit of normal for the institution) Exclusion Criteria: Documented allergy to platinum compound or to other study drugs. Any previous oxaliplatin or doxorubicin treatment, except adjuvant treatment more than 12 months before the randomization. Previous liver transplantation. Patients concomitantly receiving any other anti-cancer therapy, including interferon-α and herbal medicine which was approved by local authority to be used as anti-cancer medicine, except radiotherapy to non-target lesion (bone metastasis, etc) Patients who are receiving any other study treatments. Pregnant or lactating women or women of childbearing potential without proper contraceptive methods. History of other malignant diseases, except cured basal cell carcinoma of skin and cured carcinoma in-situ of uterine cervix. Central nervous system metastasis Other serious illness or medical conditions The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

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: A<br>Oxaliplatin + 5-Fluorouracil/Leucovorin | Drug: Oxaliplatin + 5-Fluorouracil/Leucovorin<br>* Day 1: Oxaliplatin 85mg/m² 2h IV infusion, leucovorin 200mg/m² 2h IV infusion, 5-fluorouracil 400mg/m² IV bolus, 5-fluorouracil 600mg/m2 22h IV infusion. Day 2: Leucovorin 200mg/m² 2h IV infusion, 5-fluorouracil 400mg/m² IV bolus, 5-fluorouracil 600mg/m² 22h IV infusion. Repeated every 2 weeks<br>|
| Active Comparator: B<br>Doxorubicin | Drug: Doxorubicin<br>* Day 1: Doxorubicin 50mg/m² iv infusion. Repeated every 3 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | From the date of randomization to the date of death due to any cause | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression |  | From the date of randomization to documentation of progression | 
| Response rate, secondary resection rate, quality of life |  | From the date of randomization to the end of study |