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

Liver Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00079027
• Other study ID #: CDR0000353298
• Secondary ID: CRUK-HEP-1EU-203
• Status: Active, not recruiting
• Phase: Phase 3
• First received: March 8, 2004
• Last updated: December 17, 2013
• Start date: April 2004

Study information

• Verified date: May 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 280
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Liver Cancer
• Liver Neoplasms

Intervention

Drug:
• doxorubicin hydrochloride

Procedure:
• hepatic artery embolization

Locations

Country	Name	City	State
United Kingdom	Cancer Research UK Clinical Trials Unit - Birmingham	Birmingham	England
United Kingdom	Bristol Haematology and Oncology Centre	Bristol	England
United Kingdom	Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust	Cambridge	England
United Kingdom	Royal Infirmary Edinburgh	Edinburgh	Scotland
United Kingdom	Royal Infirmary of Edinburgh at Little France	Edinburgh	Scotland
United Kingdom	West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	Royal Liverpool University Hospital	Liverpool	England
United Kingdom	Hammersmith Hospital	London	England
United Kingdom	Freeman Hospital	Newcastle-Upon-Tyne	England
United Kingdom	Royal South Hants Hospital	Southampton	England

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Birmingham

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival			No
Secondary	Overall response			No
Secondary	Quality of life as assessed by EORTC QOL QLQ-30 and EORTC QLQ HCC18 at baseline and 10 and 24 weeks			No
Secondary	Time to progression as assessed by RECIST criteria			No
Secondary	Toxicity			Yes
Secondary	Health economics			No
Secondary	Proteomic and immunological analysis			No