Bevacizumab in Advanced Hepatocellular Carcinoma

Phase II Study Evaluating the Efficacy of Bevacizumab (Avastin@) in Hepatocellular Carcinoma Not Amenable to Curative Treatment

Primary liver cancer (hepatocellular carcinoma) is the fifth most common malignant disorder, with an increasing incidence in Europe and the USA as a result of the high prevalence of hepatitis C. Most patients are not suitable for potentially curative treatment. There is no standard palliative treatment for patients with advanced hepatocellular carcinoma (HCC), as no drug has been demonstrated to be efficient in this disease in terms of survival. The use of anti-vascular agents might be a promising approach in view of the highly vascular nature of this tumor. The aim of this phase II trial is to evaluate the potential benefit of bevacizumab in terms of disease control rate, progression-free and overall survival in adult patients with advanced primary liver cancer. Bevacizumab is an angiogenesis inhibitor already successfully used in patients with colorectal and renal cancers.

Study Overview

• Status: Unknown
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: bevacizumab

• Study Type: Interventional
• Enrollment: 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Villejuif, France, 94800
    • Recruiting
    • Institut Gustave Roussy
    • Contact: Valérie BOIGE, Dr; Phone Number: 00 33 014 211 43 08; Email: boige@igr.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically proven HCC or alpha-fetoprotein level > 400 ng/ml together with hypervascular tumor and cirrhosis documented by CT scan or MRI.
• HCC not amenable to curative treatment (resection, transplantation, percutaneous ablation)
• Presence of at least one dimensionally measurable target lesion with largest diameter >= 2 cm.
• No previous chemoembolization, no previous radiotherapy
• Cancer of the Liver Italian Program (CLIP) score < 4
• World Health Organization (WHO) performance status of 2 or less
• Life expectancy >= 3 months.
• Age >= 18 years.
• Adequate hematologic functions (neutrophil count, at least 1500 per cubic millimeter; platelet count, at least 75,000 per cubic millimetre; Hemoglobin, at least 8 g/dl)
• Adequate liver function (bilirubin, not more than 2 times the upper limit of normal); Adequate renal function (serum creatinine, less than 150 micromol per liter)
• Adequate coagulation function
• Written informed consent

Exclusion Criteria:

• Decompensated cirrhosis (Child-Pugh score > 7)
• CLIP score > 4
• Variceal bleeding during the previous 3 months
• Thromboembolic event during the previous 6 months
• Medical condition requiring full dose anticoagulation or anti-platelet drugs
• Abnormal cardiac function with history of ischemic heart disease in the previous 6 months, uncontrolled hypertension, unstable angina, severe cardiac arrhythmia,
• No brain metastasis, No bone metastasis only
• Previous or current malignancies at other sites
• No concomitant antitumor treatment including tamoxifen or somatostatin analogs
• Unstable systemic diseases or active uncontrolled infections.
• Patients (male and female) not using effective contraception if of reproductive potential.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
The main response parameter will be the disease control rate, defined by the objective response and stable disease rate (Response Evaluation Criteria in Solid Tumors [RECIST criteria]) after two consecutive tumor evaluations during treatment.

Secondary Outcome Measures

Outcome Measure
Overall survival, progression-free survival, toxicity (National Cancer Institute-Common Toxicity Criteria Version 3 [NCI-CTC V3])
Evaluation of vascular changes will be performed using Doppler ultrasound with injection of sonographic contrast agent

Collaborators and Investigators

• Sponsor: Gustave Roussy, Cancer Campus, Grand Paris
• Collaborators: Hoffmann-La Roche
• Investigators: Principal Investigator: Valérie BOIGE, Dr, Gustave Roussy, Cancer Campus, Grand Paris

Publications and helpful links

General Publications

• Boige V, Malka D, Bourredjem A, Dromain C, Baey C, Jacques N, Pignon JP, Vimond N, Bouvet-Forteau N, De Baere T, Ducreux M, Farace F. Efficacy, safety, and biomarkers of single-agent bevacizumab therapy in patients with advanced hepatocellular carcinoma. Oncologist. 2012;17(8):1063-72. doi: 10.1634/theoncologist.2011-0465. Epub 2012 Jun 15.

Study record dates

Study Major Dates

• Study Start: May 1, 2005

Study Registration Dates

• First Submitted: September 8, 2005
• First Submitted That Met QC Criteria: September 8, 2005
• First Posted (Estimate): September 13, 2005

Study Record Updates

• Last Update Posted (Estimate): September 8, 2006
• Last Update Submitted That Met QC Criteria: September 7, 2006
• Last Verified: September 1, 2006

More Information

Terms related to this study

• Keywords: Hepatocellular carcinoma, advanced, bevacizumab, phase II, VGEF, neovascularization
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: IGR 1123; HCC-Avastin