Stereotactic Body Radiation Therapy (SBRT) Versus Trans-Arterial Chemoembolization (TACE) as Bridge to Liver Transplant

Study Overview
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Brief Summary
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This study will compare stereotactic body radiation therapy (SBRT) to trans-arterial chemoembolization (TACE) as a bridging strategy for patients with HCC undergoing orthotopic liver transplantation. We propose that SBRT will be associated with longer time intervals between initial treatment and the need for retreatment, compared to TACE, as a bridge to orthotopic liver transplantation.

Detailed Description
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For patients with hepatocellular carcinoma (HCC) who are waiting for a liver transplant, local treatment of their disease has become the standard of care in an effort to decrease dropout rates and as a means of reducing tumor recurrence after transplantation. However, the best modality for patients undergoing treatment as a bridge to transplantation is unclear. This study will compare stereotactic body radiation therapy (SBRT) to trans-arterial chemoembolization (TACE) as a bridging strategy for patients with HCC undergoing orthotopic liver transplantation. We propose that SBRT will be associated with longer time intervals between initial treatment and the need for retreatment, compared to TACE, as a bridge to orthotopic liver transplantation.

Official Title
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A Randomized Phase II Study of Individualized Stereotactic Body Radiation Therapy (SBRT) Versus Trans-Arterial Chemoembolization (TACE) With DEBDOX Beads as a Bridge to Transplant in Hepatocellular Carcinoma.

Conditions
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Hepatocellular Carcinoma, HCC

Intervention / Treatment
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* Radiation: Stereotactic Body Radiation Therapy (SBRT)
* Procedure: Trans-Arterial Chemoembolization (TACE)
* Drug: Doxorubin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients with hepatocellular carcinoma are eligible for this trial. Hepatocellular carcinoma is defined as having at least one of the following: Biopsy proven hepatocellular carcinoma (HCC); or A discrete hepatic tumor(s) as defined by the Barcelona (29) criteria for cirrhotic patients, >2cm with arterial hypervascularity and venous or delayed phase washout on CT or MRI. Patient is within Milan Criteria and listed for orthotopic liver transplantation. Patients must have a Zubrod performance status of ≤2. Patients must have a life expectancy of at least 12 weeks. Patients must be 18 years of age or older. Adult patients of all ages, both sexes and all races will be included in this study. Patients must be Child-Turcotte-Pugh (CTP) Class A or Class B (≤ 7). Female patients within reproductive years may not be, nor become, pregnant during participation in this study. Both male and female patients within reproductive years must agree to use an effective contraceptive method during treatment. Women of childbearing age will be required to undergo a urine or serum pregnancy test to ensure they are not pregnant. Patients must have adequate organ function within 2 weeks of enrollment. Bone marrow: Platelets ≥30,000/mm3 Renal: BUN ≤40 mg/dl; creatinine ≤2.0 mg/dl Hepatic: INR ≤ 1.5 or correctable by Vitamin K, unless anti- coagulated for another medical reason Bilirubin < 3 mg/dl (in the absence of obstruction or pre-existing disease of the biliary tract, e.g. primary sclerosing cholangitis) Patients uninvolved liver volume will be estimated and must be > 700ml. Patients must sign an informed consent form approved for this purpose by the Institutional Review Board (IRB) of the Lahey Hospital and Medical Center indicating that they are aware of the investigational aspects of the treatment and the potential risks. Exclusion Criteria Patients in a special category designated the Public Health Service, including patients younger than 18, pregnant women, and prisoners. Refractory ascites or ascites that requires paracentesis for management. Patients with a solitary lesion greater than 5.0cm in size or more than 2 discrete lesions the largest greater than 3.0 cm in size. Known allergy to intravenous iodinated contrast agents unresponsive to prednisone pre-treatment.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Arm A<br>Stereotactic Body Radiation Therapy (SBRT) | Radiation: Stereotactic Body Radiation Therapy (SBRT)<br>* SBRT will be delivered in five total fractions, with at a minimum of one day between any two treatments. The entire treatment must be delivered within 15 total days.<br>* Other names: Radiation Therapy;|
| Other: Arm B<br>Trans-Arterial Chemoembolization (TACE) Drug: Doxorubin | Procedure: Trans-Arterial Chemoembolization (TACE)<br>* First day will be administered and a second TACE will be administered after 4 weeks and subsequently if imaging is showing disease progression. Following each TACE procedure all patients will remain in hospital for observation.<br>* Other names: Chemoembolization;Drug: Doxorubin<br>* This procedure will be completed with 2 vials of drug eluting beads each loaded with 50 mg of Doxorubin.<br>* Other names: Doxorubin bead therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first additional intervention to the treated lesions |  | 1 year post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  | At each treatment, 2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment | 
| Number of further interventions |  | 2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment | 
| Pathologic response of treated lesion(s) |  | After liver transplant | 
| Radiologic response of treat lesion(s) |  | Baseline, 2 months post-treatment, 5 months post-treatment, every 3 months thereafter until 2 years post treatment | 
| Quality of Life |  | Baseline, during treatment, 2 months post-treatment, 5 months post-treatment, every 3 months until 24 months post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular carcinoma (HCC), Orthotopic liver transplant, Bridge to transplant, stereotactic body radiation therapy (SBRT), trans-arterial chemoembolization (TACE)