SBRT for Hepatocellular Carcinoma Patients With Partial Response to TACE

Study Overview
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Brief Summary
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This is a pilot study where patients with Hepatocellular Carcinoma (HCC) that have failed Transarterial Chemoembolization (TACE) will be treated with Stereotactic Body Radiation Therapy (SBRT). The focus of the study will be to evaluate safety and efficacy in our population of patients.

Official Title
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Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma Patients With Partial Response to Transarterial Chemoembolization

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Radiation: SBRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HCC diagnosis according to the American Association for the Study of Liver Diseases (AASLD) 2010 criteria Tumor Stage liver only disease tumor thrombus at segment is allowed no extra hepatic metastases tumor encompassing less than 50% of hepatic volume previous treatment with Transarterial Chemo Embolization (TACE) - patient must have performed at least 2 sessions of TACE and have signs of viable tumor in CT or MRI performed 30-40 days after last TACE presence of measurable lesion (at least one lesion that can be measured equal or more than 1 cm in CT or MRI). Maximum lesion size of 10 cm. Liver residual volume equal or more than 700cc or 40% of total liver volume Child-Pugh A or absence of hepatic cirrhosis absence of encephalopathy or ascitis on clinical exam Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Lab exams: hemoglobin > or equal 8 mg/dl neutrophils > or equal 1.200/mm³ platelets > or equal 45.000/mm³ alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than 6 times the upper normal limit bilirubin equal or < 2 mg/dl international normalized ratio (INR) < 1.7 serum creatinine equal or < 1.5 times the upper normal limit or creatinine clearance > or equal 60 ml/min Albumin >2.8 mg/dl not being pregnant - a negative pregnancy test is required (for women). Patients in fertile age should use a contraceptive method during treatment and 4 months after. Exclusion Criteria: Patients with more than 5 discrete lesions in the liver Main or common biliary duct invasion Patients with main portal vein tumor thrombus or more than 2 portal branch thrombus Patients in systemic treatment (sorafenib, chemotherapy). There should be an interval of at least 4 weeks between any medication for treatment of HCC and the current study treatment Previous radiation to upper abdomen Patients with other malignant neoplasms or previous malignant neoplasms will be accepted in the study if HCC prognosis is worse Patients with ischemic myocardial infarction within the last 6 months Patients with large esophageal varices with red color sign or bleeding within the last 3 months Patients with symptoms of colitis, enteritis, esophagitis, fistula, ileus, necrosis, stenosis or ulcer Patients with severe anorexy, constipation, dehydration, diarrhea or vomiting Patients unable to understand and sign written informed consent
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: SBRT<br>SBRT according to the intervention description | Radiation: SBRT<br>* SBRT will be prescribed according to the Radiation Therapy Oncology Group (RTOG) 1112 protocol using Mean Liver Dose (MLD) as parameter. MLD will be calculated using Liver minus Gross Tumor Volume (GTV). Prescription dose will follow the scheme below: Prescription dose(Gy) / (MLD) (Gy) 50 / 13 45 / 15 40 / 15 35 / 15.5 30 / 16 27.5 / 17 If the dose constraints cannot be met, prescription will be according to the level immediately bellow. Treatment will be delivered in 5 fractions in consecutive working days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Progression Free Survival | Local Progression Free Survival will be measured on triphasic Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) when clinically indicated. The exam will be performed every 3 months after the end of treatment. The tumor response will be measured according to the modified RECIST (mRECIST) directed to the HCC study. Local Progression Free Survival will be defined as increase of 20% in the sum of all diameters of the treated lesions. Time-to-event will be counted from the initiation of SBRT | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distant Progression Free Survival | Distant Progression Free Survival will be measured on triphasic Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) when clinically indicated. The exam will be performed every 3 months after the end of treatment. The tumor response will be measured according to the modified RECIST (mRECIST) directed to the HCC study. Distant Progression Free Survival will be defined as the appearance of a new hepatic lesion, tumoral thrombus or distant metastases. Time-to-event will be counted from the initiation of SBRT | 5 years | 
| Toxicity | Toxicity will be evaluated according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0). Toxicity will be evaluated weekly during treatment, monthly in the first 3 months after treatment and every 3 months after. Acute Toxicity will be defined as toxicity that develops within the first 3 months after initiation treatment. Chronic Toxicity will be defined as toxicity that develops after 3 months of initiation of treatment. | 5 years | 
| Overall Survival | Time-to-event will be counted from the initiation of SBRT | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carcinoma, Hepatocellular, SBRT