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International Randomized Study of Transarterial Chemoembolization Versus CyberKnife® for Recurrent Hepatocellular Carcinoma

Phase 3
18 Years
Not Enrolling
Recurrent Hepatocellular Carcinoma

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Trial Information

International Randomized Study of Transarterial Chemoembolization Versus CyberKnife® for Recurrent Hepatocellular Carcinoma

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.

Surgical resection and/or transplantation remain the only curative options. However, more
than 80% of patients present with unresectable disease. For these patients with
unresectable tumors, a variety of treatment options are available, including transarterial
chemoembolization (TACE), radiofrequency ablation (RFA), 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 significant 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 conventional radiotherapy as a means of intensifying local therapy, with
evidence of efficacy.

TACE remains the dominant mode of local therapy for unresectable HCC. However, recurrence
rates are high. Because SBRT is rapidly becoming an accepted local therapy for hepatic
lesions, its role in treating HCC needs to be further defined. Moreover, once patients have
recurred after initial TACE, it is unclear if additional TACE will be as effective or if
another mode of local therapy such as SBRT would be preferable.

We propose to conduct a multicenter randomized study comparing TACE vs. SBRT using
CyberKnife for locally recurrent HCC. Locally recurrent HCC will include lesions that
persist, progress or recur minimum 3 months after initial TACE.

Inclusion Criteria:

- Confirmed hepatocellular carcinoma by one of the following:

1. Histopathology

2. 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

1. 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 contrast liver CT

2. A recent serum AFP must 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 7.5 cm as long as the
dose constraints to normal tissue can be met.

- Eastern Clinical Oncology Group performance status 0, 1 or 2 (Appendix I).

- Patients with liver disease classified as Child Pugh class A/B, if Child's class B,
score must be 8 or less.

- Life expectancy >= 6 months

- Age >= 18 years old

- Albumin >= 2.5 g/dL

- Total Bilirubin <= 3 mg/dL

- INR <= 1.5

- Creatinine <= 2.0 mg/dL

- Both men and women and members of all races and ethnic groups are eligible for this

- 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 tumor

- Prior radiotherapy to the upper abdomen

- Prior RFA to index lesion

- Liver transplant

- Tumors greater than 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 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Freedom from local progression

Outcome Description:

Freedom from local progression at time T is defined as lack of local progression in the treated liver lesion in the set of patients alive and on study at time T and without distant progression up to time T.

Outcome Time Frame:

12 months

Safety Issue:


Principal Investigator

Albert Koong, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Stanford Comprehensive Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

February 2011

Completion Date:

February 2016

Related Keywords:

  • Recurrent Hepatocellular Carcinoma
  • Primary liver cancer
  • Hepatocellular carcinoma
  • CyberKnife
  • Accuray
  • TACE
  • Transarterial chemoembolization
  • Carcinoma
  • Carcinoma, Hepatocellular



Stanford Comprehensive Cancer Center Stanford, California  94305