RATIONALE: Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping the cells from dividing. Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs near the tumor. It is not yet known whether doxorubicin is more effective with or without chemoembolization in treating unresectable hepatocellular carcinoma (liver cancer).

PURPOSE: This randomized phase III trial is studying doxorubicin alone to see how well it works compared to doxorubicin and chemoembolization in treating patients with advanced liver cancer than cannot be removed by surgery.

Condition	Treatment or Intervention	Phase
advanced adult primary liver cancer adult primary hepatocellular carcinoma	Drug: doxorubicin  Drug: gelatin sponge, absorbable  Drug: iodized oil  Procedure: chemotherapy  Procedure: embolization therapy	Phase III

Further Study Details: 

OBJECTIVES: Primary

• Compare the survival of patients with advanced unresectable primary hepatocellular carcinoma treated with intravenous doxorubicin vs doxorubicin chemoembolization.

Secondary

• Compare the response rate in patients treated with these regimens.
• Compare time to progression in patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Compare the quality of life of patients treated with these regimens.
• Compare the health economic implications of these regimens in these patients.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to participating center, stage of disease, and alpha-fetoprotein levels (< 500 ng/mL vs ≥ 500 ng/mL). Patients are randomized to 1 of 2 treatment arms.

• Arm I (control arm): Patients receive doxorubicin IV over 3-5 minutes on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
• Arm II (chemoembolization arm): Patients undergo intra-arterial chemoembolization with iodized oil (lipiodol) and doxorubicin emulsion and a particulate material (e.g., Spongostan, Trufil, or Contour). Chemoembolization repeats every 8 weeks for a total of 3 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline and at weeks 10 and 24.

Patients are followed at 4 weeks and then every 8 weeks thereafter.

PROJECTED ACCRUAL: A total of 280 patients (140 per treatment arm) will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed hepatocellular carcinoma (HCC)
• Advanced, unresectable disease
• At least 1 unidimensionally measurable lesion
• At least 20 mm by conventional CT scan
• No clinically significant ascites
• No modified Child-Pugh class C liver disease

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Hemoglobin ≥ 8.5 g/dL
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin < 2.92 mg/dL
• Transaminases < 2.5 times upper limit of normal (ULN)
• INR < 1.5

Renal

• Creatinine < 2 times ULN

Cardiovascular

• No New York Heart Association class III or IV cardiac disease
• No acute angina
• No significant peripheral vascular disease
• No thrombosis of main portal vein
• LVEF ≥ 50%

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other concurrent serious medical condition
• No serious infection
• No psychological, familial, sociological, or geographical factors that would preclude study compliance
• No other malignancy within the past 5 years except carcinoma in situ of the cervix or non-melanoma skin cancer

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior biologic therapy for advanced unresectable HCC

Chemotherapy

• No prior systemic or regional chemotherapy
• No prior chemotherapy for advanced unresectable HCC
• No other concurrent anticancer chemotherapy

Endocrine therapy

• No prior hormonal therapy for advanced unresectable HCC

Radiotherapy

• No prior radiotherapy for advanced unresectable HCC
• No other concurrent anticancer radiotherapy

Surgery

• More than 7 days since prior major surgery
• More than 3 days since prior laparoscopy

Other

• More than 4 weeks since prior investigational agents
• No other concurrent investigational agents

United Kingdom, England
      Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust, Cambridge,  England,  CB2 2QQ,  United Kingdom; Recruiting
      Bristol Haematology and Oncology Centre, Bristol,  England,  BS2 8HW,  United Kingdom; Recruiting
      Cancer Research UK Clinical Trials Unit - Birmingham, Birmingham,  England,  B15 2TT,  United Kingdom; Recruiting
      Freeman Hospital, Newcastle upon Tyne,  England,  NE7 7DN,  United Kingdom; Recruiting
      Hammersmith Hospital, London,  England,  W12 OHS,  United Kingdom; Recruiting
      Royal Liverpool University Hospital, Liverpool,  England,  L69 3GA,  United Kingdom; Recruiting
      Royal South Hants Hospital, Southampton,  England,  SO14 0YG,  United Kingdom; Recruiting
United Kingdom, Scotland
      Royal Infirmary Edinburgh, Edinburgh,  Scotland,  EH3 9YW,  United Kingdom; Recruiting
      Royal Infirmary of Edinburgh at Little France, Edinburgh,  Scotland,  EH16 4SA,  United Kingdom; Recruiting

Study chairs or principal investigators

O. James Garden,  Study Chair,  Royal Infirmary of Edinburgh at Little France   

Study ID Numbers:  CDR0000353298; CRUK-HEP-1; EU-20340; NCT00079027
Record last reviewed:  November 2004
Last Updated:  April 4, 2005
Record first received:  March 8, 2004
ClinicalTrials.gov Identifier:  NCT00079027
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08