Chemoembolization Using Doxorubicin in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery

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 stopping them from dividing. Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs near the tumor. PURPOSE: This clinical trial is studying how well chemoembolization using doxorubicin works in treating patients with liver cancer that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Determine, preliminarily, the feasibility of chemoembolization with GelSpheres™ beads mixed with doxorubicin hydrochloride in patients with unresectable hepatocellular carcinoma. OUTLINE: This is a pilot study. Patients undergo catheterization of the hepatic artery followed by chemoembolization comprising an infusion of GelSpheres™ beads mixed with doxorubicin hydrochloride into the target hepatic artery. Patients may receive up to 3 chemoembolization treatments. After completion of study treatment, patients are followed at 1 month, every 2 months for 1 year, and then every 3 months during year 2. PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Official Title
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Treatment of Patients With Hepatocellular Carcinoma Using Drug-Eluting Bead Embolization

Conditions
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Liver Cancer

Intervention / Treatment
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* Device: Drug-eluting beads loaded with doxorubicin hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of hepatocellular carcinoma (HCC) according to the European Association for the Study of Liver (EASL) disease diagnostic criteria AND the Okuda staging classification No advanced disease, as defined by any of the following: Barcelona Clinic Liver Cancer (BCLC) class C disease, as defined by the following: Vascular invasion, including segmental portal obstruction Extrahepatic spread Cancer-related symptoms (PST of 1-2) BCLC class D disease, as defined by the following: Okuda stage III disease World Health Organization (WHO) performance status 3 or 4 Diffuse HCC, defined as massive ill-defined tumor involvement Child-Pugh Class C Not eligible for radical therapies (e.g., resection, liver transplantation, or percutaneous therapies) No significant liver decompensation Preserved liver function (Child-Pugh class A-B) No ascites (trace ascites allowed) No other active primary tumor Arteries supplying the lesion must be large enough to accept GelSpheres™ beads PATIENT CHARACTERISTICS: Bilirubin ≤ 3 mg/dL Albumin > 2.0 g/dL Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 times the upper limit of normal (ULN) Alkaline phosphatase ≤ 5 times the upper limit of normal (ULN) No active gastrointestinal bleeding No encephalopathy No contraindication to hepatic embolization procedures, as indicated by any of the following: Porto-systemic shunt Hepatofugal blood flow Platelet count < 50,000/mm^3 International normalized ratio (INR) ≥ 1.8 Partial thromboplastin time (PTT) ≥ 39 seconds Renal failure Severe atheromatosis No contraindication to doxorubicin hydrochloride administration, as indicated by any of the following: Bilirubin > 5 mg/dL White blood cell (WBC) < 1,500/mm^3 Ejection fraction < 50% by isotopic ventriculography or echocardiography Not pregnant No known allergy to contrast media No intolerance to occlusion procedures No vascular anatomy or bleeding that would preclude catheter placement or emboli injection, as indicated by any of the following: Active or risk of hemorrhage Patent extra-to-intracranial anastomoses or shunts End arteries leading directly to the cranial nerves Feeding arteries smaller than distal branches from which they emerge Collateral vessel pathways that would potentially endanger normal territories during embolization PRIOR CONCURRENT THERAPY: No prior anticancer therapy for HCC

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug-eluting bead transarterial chemoembolization (DEB-TACE)<br>Patients undergo DEB-TACE procedures utilizing LC Beads, polyvinyl alcohol microspheres with diameters of 100-300um or 300-500um, which are loaded with 100mg of doxorubicin hydrochloride and mixed with an equal volume of nonionic contrast media. | Device: Drug-eluting beads loaded with doxorubicin hydrochloride<br>* Doxorubicin eluting beads<br>* Other names: LC Beads;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Safety was assessed using the CTCAE v 3.0 criteria, reported are the number of participants that experienced at least 1 event that was grade 2 (moderate) or higher. | 1 month | 
| Safety | Safety was assessed using the CTCAE v 3.0 criteria, reported are the number of participants that experienced at least 1 event that was grade 2 (moderate) or higher. | 6 months | 
| Efficacy - Tumor Response by the European Association for the Study of the Liver (EASL) Criteria | Efficacy as assessed by radiographic tumor response using EASL criteria at baseline and at 1 month post-TACE Complete Response (CR): Achieving 100% tumor necrosis of targeted lesions Partial Response (PR): Demonstrating greater than 50% tumor necrosis in targeted lesions Progressive Disease (PD): Reappearance of or increased tumor enhancement greater than 25% in targeted lesions Stable Disease (SD): Not meeting requirements for CR or PR and not demonstrating evidence of progression in targeted lesions. | 1 month | 
| Efficacy - Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | Efficacy as assessed by radiographic tumor response using RECIST criteria at baseline, 1 month post treatment. Complete Response (CR): Disappearance of all lesions targeted by therapy Partial Response (PR): At least 30% decrease in the sum of longest diameter (LD) of lesions targeted by therapy Progressive Disease (PD): At least 20% increase in sum of LD of lesions targeted by therapy Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for PD. | 1 month | 
| Efficacy - Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | Efficacy as assessed by radiographic tumor response using RECIST criteria at baseline, and at 6 months post treatment. Complete Response (CR): Disappearance of all lesions targeted by therapy Partial Response (PR): At least 30% decrease in the sum of longest diameter (LD) of lesions targeted by therapy Progressive Disease (PD): At least 20% increase in sum of LD of lesions targeted by therapy Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for PD. | 6 months | 
| Efficacy - Overall Survival | Presented are the counts of patients that have survived up to 1 year. | 1 Year | 
| Efficacy - Overall Survival | Presented are the counts of patients that have survived up to 2 years. | 2 Years | 

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