LC Drug Eluting Bead for Treatment of Liver Cancer Which Cannot be Surgically Removed

Study Overview
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Brief Summary
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Advanced HCC represents a high unmet medical need with a poor prognosis and few therapeutic options. Patients who present with HCC beyond the currently accepted Milan criteria are not eligible to be listed for liver transplantation. The proposed study offers local regional therapy to a defined population of patients beyond Milan criteria as an attempt to downstage them to eligibility for liver transplant.

Detailed Description
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LC BeadTM is a new product specifically designed for TACE. LC BeadTM microspheres can be loaded with doxorubicin (Trade name: adriamycin), a chemotherapeutic anthracycline glycolide agent widely accepted for treatment of HCC. This novel bead slowly releases the ionically bound chemotherapeutic agent rather than administering a bolus of chemotherapy as is the case with many alternative methods of TACE. Thus, the LC BeadTM offers the potential advantage of less toxicity and prolonged tumor exposure. This study offers local regional therapy to a defined population of patients beyond transplant criteria as an attempt to downstage them to eligibility for liver transplantation. This study will make an important contribution to understanding the beads' local effect as seen in the explanted livers of those patients who go on to receive a liver transplant. Additionally, we will examine the impact of this novel treatment tool on patients' quality of life.

Official Title
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LC Drug Eluting Bead for Regional Chemoembolization to Downstage Unresectable Hepatocellular Carcinoma (HCC) to Liver Transplantation

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: LC Bead loaded with doxorubicin


Participation Criteria
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Eligibility Criteria
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Adults patients (≥ 18 years of age) with a diagnosis of HCC that is not amenable to surgical resection or local ablative therapy Histological confirmed HCC or clinical/laboratory diagnosis of HCC or nodules larger than 2cm with typical vascular features or AFP > 200 Patient must have one lesion < 8cm or up to five lesions with total diameter < 8cm Quantifiable disease limited to the liver; 40% of liver must be free of tumor burden Patient must have at least one tumor lesion that meets both of the following criteria: Lesion can be accurately measured in at least one dimension according to RECIST criteria Lesion has not been previously treated with surgery, radiation therapy, radiofrequency ablation, percutaneous ethanol or acetic acid injection, or cryoablation. ECOG performance status ≤ 2 No prior systemic chemotherapy At least 4 weeks since prior TACE or interferon Not pregnant No significant baseline liver dysfunction. Child-Pugh class A and B 7-8 (in abscence of ascites) No significant renal impairment (creatinine clearance < 30mL/minute) or patients on dialysis No current infections requiring antibiotic therapy Not on anticoagulation or suffering from a known bleeding disorder No unstable coronary artery disease or recent MI The following laboratory parameters Hemoglobin ≥ 8.5g/dL Total bilirubin ≤ 3.0mg/dL ALT and AST ≤ 5x upper limit of normal Serum creatinine ≤ 1.5x upper limit of normal INR ≤ 1.5 or a PT/PTT within normal limits Platelet count ≥ 50,000/uL Ability to understand the protocol and to agree to and sign a written informed consent document Exclusion Criteria: HCC with gross vascular invasion or extrahepatic disease Previous or concurrent cancer that is distinct in primary site or histology from HCC except cervical carcinoma in situ, treated basal-cell carcinoma of the skin, superficial bladder tumors (Ta, Tis & T1), and any cancer curatively treated > 3 years prior to entry is permitted Renal failure requiring dialysis Child-Pugh B9 or C hepatic impairment History of cardiac disease: NYHA class 2 congestive heart failure, active coronary artery disease, cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin, and uncontrolled hypertension. Myocardial infarction more than 6 months prior to study entry is permitted. Active clinically serious infections (> CTCAEv3 grade 2) Known history of HIV Known central nervous system tumors including metastatic brain disease History of organ allograft Substance abuse (current), psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results. Allergy to the investigational agents or any agent given in association with this trial. Pregnant or breast-feeding patients. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial. Uncontrolled hypertension defined as systolic blood pressure > 150mmHg or diastolic blood pressure > 90mmHg Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug Serious non-healing wound, ulcer, or bone fracture Any contraindication for doxorubicin administration: serum bilirubin > 3mg/dL WBC < 3000 cells/mm3 neutrophil < 1500 cells/mm3 cardiac ejection fraction < 50 percent assessed by isotopic ventriculography, echocardiography or MRI MUGA scan < 40% ejection fraction Any contraindication for hepatic embolization procedures Excluded therapies and medications, previous and concomitant: Prior use of any systemic anti-cancer chemotherapy for HCC Prior use of any systemic investigational agents for HCC Major surgery within 6 weeks of start of study drug Radiotherapy during study or within 3 weeks prior to start of study drug Use of biological response modifiers such as granulocyte colony-stimulating factor (G-CSF)within 3 weeks prio to study entry Autologous bone marrow transplant or stem cell rescue within four months of study drug initiation Concomitant treatment with rifampin or St. John's wort

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LC Drug Eluting Bead, Regional Chemoembolization<br>Use of LC Drug-Eluting Beads for chemoembolization will provide a method for downstaging patients with hepatocellular carcinoma which is not amenable to surgical resection or local ablative therapy to liver transplant eligibility | Drug: LC Bead loaded with doxorubicin<br>* LC Bead is a new product specifically designed for TACE. LC Bead microspheres will be loaded with between 50-100mg of doxorubicin for each of several TACE procedures. The bead will utilize embolic induced ischemia as well as local chemotherapy in an effort to downstage unresectable HCC to liver transplantation<br>* Other names: LC Bead;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Patients in the Cohort Effectively Downstaged to Transplant Eligibility With the LC BeadTM | Advanced HCC represents a high unmet medical need with a poor prognosis and few therapeutic options. Patients who present with HCC beyond the currently accepted Milan criteria are not eligible to be listed for liver transplantation. The proposed study offers local regional therapy to both a defined population of patients beyond Milan criteria as an attempt to downstage them to eligibility for liver transplant as well as those individuals within Milan criteria as an attempt to maintain their eligibility. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Objective Tumor Response Rate in Patients With HCC Treated With LC BeadTM Using EASL and RECIST Criteria |  | 36 months | 
| Symptomatic and Quality-of-life Measures in Patients Treated With the LC BeadTM |  | 36 months | 
| The Local Effects of the LC BeadTM in the Explanted Liver of Those Patients Who go on to Receive Liver Transplantation |  | 36 months |