Transarterial Chemoembolization vs CyberKnife for Recurrent Hepatocellular Carcinoma

Study Overview
=================
Brief Summary
-----------------
Primary Objective: To compare the efficacy of TACE vs. CyberKnife SBRT in the treatment of locally recurrent HCC after initial TACE. Secondary Objectives: To determine the progression-free survival of TACE vs. CyberKnife SBRT To determine the overall survival of TACE vs. CyberKnife SBRT for locally recurrent HCC To determine the toxicities associated with TACE or CyberKnife SBRT for the treatment of recurrent HCC.

Official Title
-----------------
International Randomized Study of Transarterial Chemoembolization Versus CyberKnife for Recurrent Hepatocellular Carcinoma

Conditions
-----------------
Carcinoma, Hepatocellular

Intervention / Treatment
-----------------
* Device: CyberKnife
* Procedure: TACE
* Drug: CT Contrast
* Drug: doxorubicin
* Drug: Epirubicin
* Drug: 5-fluorouracil
* Drug: Mitomycin C
* Drug: Gemcitabine
* Drug: Cisplatin
* Device: SMANCS


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Confirmed hepatocellular carcinoma by one of the following: Histopathology One radiographic technique that confirms a lesion >=2 cm with arterial enhancement with washout on delayed phase Hepatic lesion in patients for whom surgical resection is not possible or would not result in an opportunity for cure Radiographic evidence of persistent, progressive or recurrent disease in an area previously treated with TACE. This evaluation should be determined after 6 weeks of initial TACE Multi-specialty evaluation whereby the recurrent liver lesion was deemed by both the attending radiation oncologist and interventional radiologist amenable to treatment by the respective modality Eligible patients must undergo an IV contrast CT scan of the liver within 6 weeks of enrollment onto the study; a contrast enhanced liver MRI may be substituted for the IV contrast CT of the liver. A recent serum AFP must also be obtained within 4 weeks of enrollment. Unifocal liver tumors not to exceed 7.5 cm in greatest axial dimension. Multifocal lesions will be restricted to lesions that can be treated within a single target volume within the same liver segment and to an aggregate of 7.5cm as long as the dose constraints to normal tissue can be met Eastern Clinical Oncology Group performance status 0, 1 or 2 Patients with liver disease classified as Child Pugh class A/B; if Child's class B, score must be 8 or less Albumin >= 2.5 g/dL Total bilirubin <= 3 mg/dL INR <= 1.5 Creatinine <= 2.0 mg/dL Age >= 18 years old Life expectancy>= 6 months Ability of the research subject or authorized legal representative to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Prior radiation for the recurrent liver tumors Prior radiotherapy to the upper abdomen Prior RFA to index lesion Liver transplant Tumors >= 7.5 cm in greatest axial dimension Portal vein thrombus Large varices within 2 cm of index lesion (seen on cross section imaging) Contraindication to receiving radiotherapy Active gastrointestinal bleed within 2 weeks of study enrollment Ascites refractory to medical therapy Women who are pregnant Administration of any systemic chemotherapy within the last 1 month Presence of multifocal lesions located in different lobes of the liver or extrahepatic metastases Participation in another concurrent SYSTEMIC treatment protocol Prior history of malignancy other than HCC

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Device: CyberKnife|Standard of Care|
|Procedure: TACE|Standard of Care|
|Drug: CT Contrast|Standard of Care|
|Drug: doxorubicin|Standard of Care|
|Drug: Epirubicin|Standard of Care|
|Drug: 5-fluorouracil|Standard of Care|
|Drug: Mitomycin C|Standard of Care|
|Drug: Gemcitabine|Standard of Care|
|Drug: Cisplatin|Standard of Care|
|Device: SMANCS|Standard of Care|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from local progression at 6 months and 12 months |  | 6 months and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | at 6, 12 and 18 months | 
| Overall survival |  | at 6, 12, 18 months and up to 3 years | 
| Serum AFP levels |  | 1 month, 3 months, 6 months, 12 months and 18 months |