Transarterial Chemoembolization (TACE) vs. CyberKnife for Recurrent Hepatocellular Carcinoma (HCC)

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborator:
Stanford University
Information provided by (Responsible Party):
Accuray Incorporated
ClinicalTrials.gov Identifier:
NCT01318200
First received: March 16, 2011
Last updated: February 16, 2012
Last verified: February 2012
  Purpose

To compare the efficacy of Transarterial Chemoembolization (TACE) to CyberKnife stereotactic body radiotherapy in the treatment of patients with locally recurrent hepatocellular carcinoma (HCC) after TACE.


Condition Intervention Phase
Recurrent Hepatocellular Carcinoma
Procedure: Transarterial Chemoembolization
Radiation: CyberKnife SBRT
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: International Randomized Study of Transarterial Chemoembolization Versus CyberKnife® for Recurrent Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by Accuray Incorporated:

Primary Outcome Measures:
  • Freedom from local progression [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: 6, 12 and 18 months ] [ Designated as safety issue: No ]
    Progression-free survival will be defined as subject alive and free from local progression, disease recurrence elsewhere in the liver, extrahepatic progression, or clinical deterioration unattributable to another underlying medical condition in the absence of clear radiographic findings of progressive disease.

  • Overall survival [ Time Frame: Up to three years following therapy ] [ Designated as safety issue: No ]
    Overall survival will be determined as a measure of time from diagnosis of initial recurrence until death from any cause.

  • Serum AFP levels [ Time Frame: 3, 6, 12 and 18 months ] [ Designated as safety issue: No ]

    Serum AFP levels will be measured at specific points during the study. The 2 endpoints to be analyzed are:

    • Initial AFP levels
    • AFP response - the percent decrease in serum AFP levels from the initial result to the eventual nadir after therapy

    These endpoints will be correlated to the clinical endpoints (freedom from local progression, progression free-survival, and overall survival).


  • Freedom from local progression [ Time Frame: 6 and 18 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 0
Study Start Date: February 2011
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Transarterial Chemoembolization Procedure: Transarterial Chemoembolization
Transarterial Chemoembolization will be given within 12 weeks and up to 3 staged procedures, depending on the architecture of the tumor vasculature.
Active Comparator: CyberKnife SBRT Radiation: CyberKnife SBRT
Dose is 45 Gy (15 Gy in 3 fractions) or 36 Gy(12 Gy in 3 fractions). Tumors should receive the higher dose unless normal tissue constraints cannot be met.

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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 study
  • 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01318200

Locations
United States, California
Stanford Comprehensive Cancer Center
Stanford, California, United States, 94305
Sponsors and Collaborators
Accuray Incorporated
Stanford University
Investigators
Study Chair: Albert Koong, MD, PhD Stanford Comprehensive Cancer Center
Study Chair: Daniel Chang, MD Stanford Comprehensive Cancer Center
Study Chair: Nishita Kothary, MD Stanford Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Accuray Incorporated
ClinicalTrials.gov Identifier: NCT01318200     History of Changes
Other Study ID Numbers: ACCH001.0
Study First Received: March 16, 2011
Last Updated: February 16, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Accuray Incorporated:
Primary liver cancer
Hepatocellular carcinoma
CyberKnife
Accuray
TACE
Transarterial chemoembolization

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

ClinicalTrials.gov processed this record on July 24, 2014