Trial of Beads Versus Doxorubicin Eluting Beads for Arterial Embolization of Hepatocellular Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of blocking the blood vessels to the tumor in your liver with small beads alone (Bead Block) versus blocking them with the same bead that contains and releases doxorubicin (a chemotherapy agent). The reason for the study is to see if adding doxorubicin kills more tumor than would be killed by just blocking the blood supplying the tumor. The chemotherapy, doxorubicin, has been used for many years to treat patients with cancer. This procedure to block the blood vessels is called embolization. Embolization is a common treatment for patients with liver cancer who cannot have surgery. The investigators are comparing the standard treatment (using the small beads alone) with another that should be at least as good, but possibly better (with the addition of the drug, doxorubicin). There is no guarantee that the new treatment is better and it is possible that there might be more side effects (related to the doxorubicin) than what is seen with the standard treatment.

Detailed Description
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Biocompatibles LC Bead (also known as DC Bead in Asia & Europe) microspheres are preformed soft, deformable microspheres that may be loaded with doxorubicin and used to occlude blood flow to a cancerous tumour. LC Bead microspheres consist of a macromere derived from PVA. The fully polymerized microsphere is approximately 90% water and is compressible to approximately 30% by diameter. The microspheres can be delivered through conventional catheters (4-5Fr) or micro-catheters in the 2-3Fr range. These microspheres, like all agents used for arterial embolization, are mixed with radiographic contrast prior to administration in order to allow for fluoroscopic control of the embolization procedure.

Official Title
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A Randomized Single Blind Controlled Trial of Beads vs. Doxorubicin Eluting Beads for Arterial Embolization of Hepatocellular Carcinoma (HCC)

Conditions
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Hepatocellular Carcinoma, Liver Cancer, Hepatoma

Intervention / Treatment
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* Device: Bead Block microspheres
* Other: Bead + Dox Arm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with a confirmed diagnosis of HCC according to EASL criteria for diagnosis; who is not a surgical resection candidate, or refuses surgery Patient must be 18 years of age or older Patient must be Okuda stage I or II Patient must have an ECOG performance status of 0 or 1 No prior chemotherapy or biotherapy within 4 weeks of scheduled embolization, with all toxicities, if any, resolved to grade < than or = to 1 Patient must have the following laboratory values confirmed within 14 days of registration: Creatinine ≤ than or = to 2.0 the institution ULN Platelets ≥ than or = to 50,000/mm3 INR ≤ than or = to 2.0 for patients who are not on Coumadin aPTT < or = to twice control Bilirubin < 3 mg/dl WBC > 3000 cells/mm3 ANC > 1500 cells/mm3 Negative serum pregnancy test (Female of childbearing potential only) Exclusion Criteria: Patient has another primary tumor, with the exception of conventional basal cell CA, superficial bladder cancer, melanoma in situ, or treated prostate cancer currently without biochemical or radiographic evidence of active disease Women who are pregnant or lactating Patient previously treated with doxorubicin Contraindication to angiography/embolization including: patients who cannot receive contrast 1.Severe allergic reaction to contrast despite pre-medication, 2. poor renal function; 3.Lack of arterial access (eg femoral artery occlusion); 4. other, based on judgment of the investigator Patient has already undergone hepatic arterial embolization for the hepatocellular cancer for which they are currently being evaluated Patient has received prior radiotherapy for the hepatocellular cancer for which they are currently being evaluated Patient has had previous local-regional treatment of the current target tumor volume Patient who cannot have CT scan Patient at very high risk for post-embolization hepatic failure: 1. Child's C cirrhosis, 2. > 75% liver replaced by tumor Cardiac exclusion for: 1. Myocardial infarction within 90 days of study, 2. uncontrolled arrhythmia, 3. LVEF < 50% for patients randomized to receive LC Bead Patients with tumors exhibiting characteristics considered contra-indications to particle embolization, including: 1. collateral vessel pathways potentially endangering normal territories during embolization, 2. arteries supplying tumor not large enough to accept LC Bead or Bead Block, 3. Presence of arterial to systemic venous shunts, 4. Presence of arterial to pulmonary vascular shunts

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
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bead Arm<br>Hepatic arterial embolization with Bead Block microspheres, beginning with 100 - 300 micron beads, and using larger particles if necessary until stasis is evident. | Device: Bead Block microspheres<br>* Bead Block (Beads) microsphere, 100-300 micron with additional larger size beads as necessary to achieve stasis<br>|
| Active Comparator: Bead + Dox Arm<br>Hepatic arterial embolization with 100-300 micron drug eluting microspheres (LC Bead) loaded with 150 mg Doxorubicin, followed by embolization with Bead Block microspheres (100-300 micron and larger size beads as necessary) until stasis is evident. | Other: Bead + Dox Arm<br>* Bead + Dox Arm: Hepatic arterial embolization with 100-300 micron drug eluting microspheres (LC Bead) loaded with 150 mg Doxorubicin, followed by embolization with Bead Block microspheres (100-300 micron and larger size beads as necessary) until stasis is evident.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to Treatment by RECIST Criteria | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | 2 to 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Evaluated for Toxicity | Toxicity will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) 3.0. | 1 year | 
| Progression Free Survival | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | 1 year | 
| Overall Survival |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver Cancer, Hepatoma, 07-099