SBRT or TACE for Advanced HCC

Study Overview
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Brief Summary
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Randomized study of stereotactic body radiation therapy (SBRT) versus transarterial chemoembolization (TACE) in locally advanced hepatocellular carcinoma.

Official Title
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Randomized Study of Stereotactic Body Radiation Therapy (SBRT) Versus Transarterial Chemoembolization (TACE) in Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: DEB
* Radiation: SBRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HCC (biopsy or radiological diagnostic (>1 cm, enhancing in arterial phase and wash-out in later phases). Number of lesions: not more than 3 lesions Lesion size: up to 10 cm for a single lesion (and up to 10 cm cumulative diameter, if there is more than 1 lesion) Child-Pugh A or B (<7) on examination within 6 weeks prior to study entry BCLC Stage A/B Must be fit (eligible) for SBRT and TACE Unsuitable/unwilling for resection or transplant or radiofrequency ablation (RFA) or if these options are not available Distance between GTV (lesion) and luminal structures (including esophagus, stomach, duodenum, small or large bowel) is >10 mm All blood work obtained within 2 weeks prior to study entry with adequate organ function defined as follows: Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 Platelets ≥50,000 cells/mm3 Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.) Total bilirubin < 2 mg/dL Prothrombin time/INR < 1.4 (unless on Coumadin/Warfarin) Albumin ≥ 28 g/L AST (and ALT) < 5 times ULN Serum creatinine ≤ ULN or creatinine clearance ≥ 60 mL/min Left-ventricular ejection fraction >50% (cardiac ejection fraction should be measured in case of history of cardio-vascular disease. May have had previous surgery, ethanol injection and RFA to the liver Exclusion Criteria: • Not suitable for clinical trial or follow-up Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 2 years (Note that carcinoma in situ of the breast, oral cavity, or cervix are all permissible). No active cancer therapy. Unsuitable for or refractory to transarterial hepatic chemo-embolization (TACE) Non-enhancing HCC on CT or CT-angio or Portal vein thrombosis/macroscopic venous invasion Arterio-portal and arterio-venous fistulas observed on pre-study imaging (if it is found during the TACE, the fistula may be embolized before injection of the drug). Evidence of metastatic disease including nodal or distant metastases. Previous TACE or radiation to the liver (including SIRT) Life-threatening condition (including untreated HIV and active hepatitis B/C) Detectable HBeAg and HBV viral load > 20,000 IU/mL or HBeAg-negative chronic hepatitis B and HBV viral load >2,000 IU/mL If HBV-DNA copy is higher than 500 copies/ml, anti-viral therapy, such as Entecavir followed by observation for 2 weeks. If anti-HCV antibody is positive (may be false positive) and increased HCV viral load indicating active disease. Active HCV should be treated sufficiently before inclusion in the study. Below 2 million copies per milliliter (mL) is related to chronic hepatitis C that does not need antiviral therapy. Patients with active hepatitis B or C should be on treatment for at least 4 weeks before inclusion in the trial On sorafenib or other antineoplastic drug therapy within 7 days before inclusion (not accepted until time of progression). Pregnancy or women of childbearing potential require a negative pregnancy test within 28 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Active Comparator: TACE<br>Transarterial chemoembolization with drug eluted beads or doxorubicin/lipiodol | Drug: DEB<br>* Infusion of DEB or doxorubin/lipiodol through catheter in the hepatic artery<br>* Other names: doxorubicin;|
| Experimental: SBRT<br>Stereotactic radiation therapy with risk adapted dose prescription | Radiation: SBRT<br>* High precision radiation therapy to the liver tumor(s)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression (total of local, intra- and extrahepatic) | Modified RECIST | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response | Modified RESIST | 3 months | 
| Local control of treated tumor | Modified RECIST | 1 year | 
| Intrahepatic failure | Intrahepatic failure (more than 1 cm away) | 1 year | 
| Extrahepatic failure | Modified RECIST | 1 year | 
| Overall survival | Overall survival | 1 year | 
| Treatment related toxicity | Tox CTC Ver 4.0 | 1 year | 
| Cost-benefit | $ spend on hospitalization and treatment of complications after the treatment | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stereotactic body radiation therapy, transarterial chemoembolization, SBRT, TACE