Doxorubicin By Infusion or Chemoembolization in Treating Patients With Advanced Unresectable Hepatocellular Carcinoma (Liver Cancer)

Study Overview
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Brief Summary
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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 given by infusion to see how well it works compared to doxorubicin given by chemoembolization in treating patients with advanced liver cancer than cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Primary Compare the survival of patients with advanced unresectable primary hepatocellular carcinoma treated with intravenous doxorubicin hydrochloride vs doxorubicin hydrochloride 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 hydrochloride 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 transarterial chemoembolization using DC Bead and doxorubicin hydrochloride. 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 12 weeks thereafter. Peer Reviewed and Funded or Endorsed by Cancer Research UK PROJECTED ACCRUAL: A total of 280 patients (140 per treatment arm) will be accrued for this study.

Official Title
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A Randomized Clinical Trial Evaluating the Benefits of Doxorubicin Chemoembolization Versus Systemic Doxorubicin in Patients With Unresectable, Advanced Hepatocellular Carcinoma

Conditions
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Liver Cancer

Intervention / Treatment
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* Drug: doxorubicin hydrochloride
* Procedure: hepatic artery embolization


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed hepatocellular carcinoma (HCC) Advanced, unresectable disease No clinically significant ascites No modified Child-Pugh class C liver disease No main portal vein occlusion/involvement No extrahepatic tumor of any kind PATIENT CHARACTERISTICS: Age 18 and over (16 and over for patients residing in Scotland) Performance status ECOG 0-2 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 < 5.0 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 More than 6 weeks since prior ablative therapy and must have radiological evidence of progression if ablated site is the only site of disease No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 18 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: doxorubicin hydrochloride|nan|
|Procedure: hepatic artery embolization|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response |  |  | 
| Quality of life as assessed by EORTC QOL QLQ-30 and EORTC QLQ HCC18 at baseline and 10 and 24 weeks |  |  | 
| Time to progression as assessed by RECIST criteria |  |  | 
| Toxicity |  |  | 
| Health economics |  |  | 
| Proteomic and immunological analysis |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced adult primary liver cancer, adult primary hepatocellular carcinoma