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

Sponsor

Sanofi (Industry)

Overall Status

Completed

CT.gov ID

NCT00471965

Collaborator

(none)

371

Enrollment

Locations

Arms

Duration (Months)

92.8

Patients Per Site

2.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary:

Overall Survival (OS)

Secondary:

Time to Tumor Progression (TTP)
Response Rate (RR)
Improvement of Quality of Life (QoL)
Safety
Secondary resection rate

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Hepatocellular	Drug: Oxaliplatin + 5-Fluorouracil/Leucovorin Drug: Doxorubicin	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

371 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2007

Actual Primary Completion Date :

Mar 1, 2010

Actual Study Completion Date :

Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A Oxaliplatin + 5-Fluorouracil/Leucovorin	Drug: Oxaliplatin + 5-Fluorouracil/Leucovorin 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
Active Comparator: B Doxorubicin	Drug: Doxorubicin Day 1: Doxorubicin 50mg/m² iv infusion. Repeated every 3 weeks.

Arm

Intervention/Treatment

Experimental: A

Oxaliplatin + 5-Fluorouracil/Leucovorin

Drug: Oxaliplatin + 5-Fluorouracil/Leucovorin

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

Active Comparator: B

Doxorubicin

Drug: Doxorubicin

Day 1: Doxorubicin 50mg/m² iv infusion. Repeated every 3 weeks.

Outcome Measures

Primary Outcome Measures

Overall survival [From the date of randomization to the date of death due to any cause]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country
1	Sanofi-Aventis Administrative Office	Shanghai	China
2	Sanofi-Aventis Administrative Office	Seoul	Korea, Republic of
3	Sanofi-Aventis Administrative Office	Taipei	Taiwan
4	Sanofi-Aventis Administrative Office	Bangkok	Thailand