Combination SBRT With TACE for Unresectable Hepatocellular Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01020812
Recruitment Status : Terminated (enrollment was too low)
First Posted : November 26, 2009
Results First Posted : May 22, 2015
Last Update Posted : July 27, 2016
Information provided by (Responsible Party):
Daniel T. Chang, Stanford University

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

Condition or disease Intervention/treatment Phase
Carcinoma, Hepatocellular Hepatobiliary Neoplasm Liver Carcinoma Procedure: TACE Procedure: SBRT Phase 1 Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Combination Stereotactic Body Radiotherapy (SBRT) With Transarterial Chemo-Embolization (TACE) for Unresectable Hepatocellular Carcinoma
Study Start Date : September 2009
Actual Primary Completion Date : March 2014
Actual Study Completion Date : March 2014

Arm Intervention/treatment
Experimental: Stereotactic body radiotherapy (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

Procedure: TACE
Standard of Care
Other Names:
  • Transcatheter arterial chemoembolization
  • Transarterial Chemoembolization

Procedure: SBRT
Standard of Care
Other Name: stereotactic body radiotherapy

Primary Outcome Measures :
  1. Freedom From Local Progression of TACE and SBRT at 12 Months [ Time Frame: 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 :
  1. To Determine the Progression-free Survival of TACE and SBRT at 18 Months [ Time Frame: 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.

  2. To Determine the Overall Survival of TACE and SBRT at 18 Months [ Time Frame: 18 months ]
    Overall survival is defined as the time from the start of treatment until death from any cause.

  3. Median Progression Free Survival [ Time Frame: 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion -

  • Liver tumors treatable by SBRT not to exceed 10cm in greatest axial dimension.

    • 800 cc of uninvolved liver
    • Patients may have additional hepatic lesions if they are <3cm and can be treated with TACE or RFA.
  • Age > 18 years old
  • Albumin > 2.4 g/dL.
  • Total bilirubin < 3 mg/dL.
  • INR ≤ 1.5.
  • Creatinine < 2.0 mg/dL.
  • Confirmed hepatocellular carcinoma by one of the following:

    • Histopathology
    • Two radiographic techniques (out of US, MRI, CT, Angiography) that confirm a lesion >2 cm with arterial hypervascularization
    • One radiographic technique that confirms a lesion >2 cm with arterial hypervascularization and an elevated AFP
  • Hepatic lesion in patients for whom surgical resection is not possible or would not result in an opportunity for cure
  • Tumor(s) <10cm
  • Eastern Clinical Oncology Group performance status 0, 1 or 2
  • No prior surgery, chemotherapy, or radiation for the current tumor
  • Patients placed on the liver transplant registry are eligible for this trial, but will be withdrawn from the protocol if they receive liver transplantation.
  • TACE done prior to study enrollment is allowed if there were no more than 3 procedures within an 18 week period and SBRT can begin within 12 weeks of the last TACE procedure.

Exclusion -

  • Prior radiotherapy to the upper abdomen
  • Prior TACE, RFA, or liver transplant
  • Tumor(s) ≥ 10cm
  • Large esophageal varices without band ligation
  • Active GI bleed or within 2 weeks of study enrollment
  • Ascites refractory to medical therapy
  • Contraindication to receiving radiotherapy
  • Women who are pregnant
  • Administration of any systemic cytotoxic agents within the last 12 months
  • Presence of extrahepatic metastases
  • Participation in another concurrent treatment protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01020812

United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Principal Investigator: Daniel T Chang Stanford University

Responsible Party: Daniel T. Chang, Associate Professor of Radiation Oncology (Radiation Therapy), Stanford University Identifier: NCT01020812     History of Changes
Other Study ID Numbers: HEP0024
SU-09112009-3882 ( Other Identifier: Stanford University )
First Posted: November 26, 2009    Key Record Dates
Results First Posted: May 22, 2015
Last Update Posted: July 27, 2016
Last Verified: June 2016

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases