Combination SBRT With TACE for Unresectable Hepatocellular Carcinoma

Phase 1

Terminated

Conditions: Carcinoma, Hepatocellular
Hepatobiliary Neoplasm
Liver Carcinoma

Interventions: Procedure: TACE
Procedure: SBRT

Registration Number: NCT01020812

Lead Sponsor: Stanford University

Brief Summary: To determine the efficacy and toxicity of TACE combined with SBRT

Detailed Description: Hepatocellular carcinoma (HCC) is the third most deadly cancer in the world. It is primarily seen in areas where hepatitis is endemic, such as Asia, but other risk factors include alcoholic cirrhosis.

Outcome of this disease is poor, mostly due to the fact that \>80% of patients present with unresectable disease. Surgery or transplantation remain the only curative options. For the vast majority of patients who are unresectable, a variety of treatment options are available, including transarterial chemo-embolization (TACE), radiofrequency ablation, radioactive microspheres, microwave coagulation, laser-induced thermotherapy, and percutaneous alcohol injection, all of which have similar survival rates. Stereotactic body radiotherapy (SBRT) for unresectable HCC is a relatively new treatment option made available because of great improvements in diagnostic imaging and radiation delivery techniques. Although follow-up is limited, results show encouraging local control rates. Some investigators have combined TACE with fractionated radiotherapy as a means of intensifying local therapy, with some evidence of benefit.

TACE remains the dominant mode of local therapy for unresectable HCC. However, recurrence rates are high. The recent randomized trial suggests that a combination of local therapy (TACE and radiofrequency ablation \[RFA\]) is superior to either therapy alone, providing proof of principle that combined local treatment is most likely more effective for HCC. Because SBRT is rapidly becoming an accepted local therapy for hepatic lesions, its role in treating HCC needs to be further defined. Studies combining TACE and external beam radiotherapy have shown encouraging results, so the logical next step is to combine TACE with SBRT, which delivers a radiobiologically more intensive dose of radiation. However, toxicity data are lacking, since this combination has not been previously reported.

We propose to conduct a trial of trans-arterial chemo-embolization (TACE) and SBRT for unresectable HCC.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 11

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Stereotactic body radiotherapy (SBRT)	SBRT	SBRT will be delivered on Varian's linear accelerator with On-Board Imaging (OBI) capabilities. The tumor will be tracked with the ethiodol material from the TACE procedure, and respiratory gating will be used to minimize motion due to respiration. Treatment will be given in either 3 or 5 fractions . SBRT will take place after the treatment planning and within 12 weeks of the last TACE procedure. Doses: 45 Gy at 15 Gy/fraction , 36 Gy at 12 Gy/fraction, 45 Gy at 9 Gy/fraction, 40 Gy at 8 Gy/fraction
Stereotactic body radiotherapy (SBRT)	TACE	SBRT will be delivered on Varian's linear accelerator with On-Board Imaging (OBI) capabilities. The tumor will be tracked with the ethiodol material from the TACE procedure, and respiratory gating will be used to minimize motion due to respiration. Treatment will be given in either 3 or 5 fractions . SBRT will take place after the treatment planning and within 12 weeks of the last TACE procedure. Doses: 45 Gy at 15 Gy/fraction , 36 Gy at 12 Gy/fraction, 45 Gy at 9 Gy/fraction, 40 Gy at 8 Gy/fraction

Primary Outcome Measures

Name	Time	Method
Freedom From Local Progression of TACE and SBRT at 12 Months	12 months	Freedom from local progression is defined as the time from start of treatment until the first occurrence of local progression. Local progression is defined as progression in the treated lesion according to the RECIST criteria. Progression outside the treated lesion and/or death will be considered as competing risks. The data was analyzed in a competing risk model with death as a competing risk. The outcome reported is the cumulative incidence at 12 months.

Secondary Outcome Measures

Name	Time	Method
To Determine the Overall Survival of TACE and SBRT at 18 Months	18 months	Overall survival is defined as the time from the start of treatment until death from any cause.
Median Progression Free Survival	18 months	Time to progression free survival is defined as the time from randomization until either death or progression of disease. The median survival was calculated using a Kaplan Meier algorithm.
To Determine the Progression-free Survival of TACE and SBRT at 18 Months	18 months	Progression free survival is defined as the time from the start of treatment until the first progression or death. Progression will be defined as either local progression, disease occurring elsewhere in the liver, extrahepatic progression or clinical deterioration attributable to another underlying medical condition in the absence of clear radiographic findings of progressive disease.