Transarterial Chemoembolization Compared With Stereotactic Body Radiation Therapy or Stereotactic Ablative Radiation Therapy in Treating Patients With Residual or Recurrent Liver Cancer Undergone Initial Transarterial Chemoembolization

International Randomized Study of Transarterial Chemoembolization (TACE) Versus Stereotactic Body Radiotherapy (SBRT) / Stereotactic Ablative Radiotherapy (SABR) for Residual or Recurrent Hepatocellular Carcinoma After Initial TACE

This randomized phase III trial studies how well transarterial chemoembolization (TACE) works compared to stereotactic body radiation therapy (SBRT) or stereotactic ablative radiation therapy (SABR) in patients with liver cancer that remain after attempts to remove the cancer have been made (residual) or has come back (recurrent). TACE is a minimally invasive, image-guided treatment procedure that uses a catheter to deliver both chemotherapy medication and embolization materials into the blood vessels that lead to the tumors. SBRT or SABR may be able to send radiation directly to the tumor and cause less damage to normal liver tissue. It is not yet known whether TACE is more effective than SBRT or SABR in treating patients with persistent or recurrent liver cancer who have undergone initial TACE.

Study Overview

• Status: Terminated
• Conditions: Recurrent Hepatocellular Carcinoma; Child-Pugh Class A; Child-Pugh Class B
• Intervention / Treatment: Radiation: Stereotactic Body Radiation Therapy; Procedure: Transarterial Chemoembolization; Drug: embolic agent; Drug: lipiodol

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the freedom from local progression (FFLP) of TACE versus (vs) SABR in patients with persistent hepatocellular carcinoma (HCC) after TACE.

SECONDARY OBJECTIVES:

I. To determine the progression-free survival (PFS) of TACE vs SABR in patients with persistent HCC after initial TACE.

II. To determine the overall survival (OS) of TACE vs SABR for persistent HCC. III. To determine the toxicities associated with TACE or SABR for persistent HCC.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients undergo TACE.

ARM II: Beginning within 2 weeks of the radiation set-up scan and within 4 weeks of fiducial seed implantation (if applicable), patients undergo image guided SBRT 3 fractions within 1 week or 5 fractions within 2 weeks.

After completion of study treatment, patients are followed up for 1-2 weeks, 1, 3, 6, 12, and 18 months, and every 6 months up to 3 years.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University, School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed hepatocellular carcinoma (HCC) by one of the following:

  • Histopathology
  • One radiographic technique that confirms a lesion >= 1 cm with arterial hypervascularization with washout on delayed phase
• Radiographic evidence of persistent, progressive, or recurrent disease in an area previously treated with TACE and determined from 3 months after initial TACE; this evaluation should be within 6 weeks of date of study eligibility
• 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 10 cm as long as the dose constraints to normal tissue can be met
• Eastern Clinical Oncology Group (ECOG) performance status 0, 1 or 2
• Patients with liver disease classified as Child Pugh class A or B, with score =< 9 ((within 4 weeks of treatment)
• Life expectancy >= 6 months
• Ability of the research subject or authorized legal representative to understand and have the willingness to sign a written informed consent document

Exclusion Criteria:

• Prior radiotherapy to the upper abdomen
• Prior radioembolization to the liver
• Prior radiofrequency ablation (RFA) to index lesion
• Liver transplant
• Active gastrointestinal bleed within 2 weeks of study enrollment
• Ascites refractory to medical therapy (mild to moderate ascites is allowed)
• Women who are pregnant or breastfeeding
• Administration of chemotherapy within the last 1 month
• Extrahepatic metastases
• Participation in another concurrent treatment protocol
• Prior history of malignancy other than HCC, dermatologic basal cell or squamous cell carcinoma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I (TACE); Patients undergo TACE.	Procedure: Transarterial Chemoembolization; Undergo TACE; Other Names: TACE; Drug: embolic agent; . Acceptable embolic agents include: Gelatin sponge (gelfoam); Polyvinyl alcohol (PVA) particles; Microspheres / Embolic beads; Drug: lipiodol
Experimental: Arm II (SBRT); Beginning within 2 weeks of the radiation set-up scan and within 4 weeks of fiducial seed implantation (if applicable), patients undergo image guided SBRT 3 fractions within 1 week or 5 fractions within 2 weeks.	Radiation: Stereotactic Body Radiation Therapy; Undergo SBRT; Other Names: SBRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Local Progression Event	Local progression event: occurring in the treated hepatic lesion.	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median OS	Overall survival will be summarized using Kaplan-Meier curves and medians with 95% confidence intervals calculated using Greenwood's formula. Log rank tests will be used to compare treatment groups. Cox proportional hazard models will be used to estimate hazard ratios between treatment groups and to assess other risk factors, in particular the effect of tumor size and the impact of the different institutions.	Time from randomization until death from any cause, assessed up to 3 years
Comparison of Median Freedom From Extra Hepatic Progression	The time to freedom from extra hepatic progression will be estimated by competing risk models with death as a competing risk. Risk factors such as tumor size and institution will be tested in a multivariate Cox regression model adjusting for the competing risks.	Up to 16 weeks
Median Extra Hepatic PFS for Patients With Tumors Smaller Than 3 cm and Greater Than 3 cm Per Treatment Group	Extra hepatic PFS within each subgroup will be summarized by cumulative incidence function estimators adjusted for the competing risk of death or regional or distant progression.	At 18 months
Median FFLP for Patients With Tumors Smaller Than 3 cm and With Tumors Greater Than 3 cm Per Treatment Group	FFLP within each subgroup will be summarized by cumulative incidence function estimators adjusted for the competing risk of death or regional or distant progression.	At 18 months
Median OS for Patients With Tumors Smaller Than 3 cm and Greater Than 3 cm Per Treatment Group	Within each subgroup OS will be summarized using Kaplan-Meier curves and medians with 95% confidence intervals calculated using Greenwood's formula.	At 18 months
Number of Participants With Disease Progression or Death	Including local, regional, or distant progression events, or death. Local progression event: occurring in the treated tumor. Regional progression event: occurring in the same part of the body as the treated tumor. Distant progression event: occurring outside the region of the body where the treated tumor is located.	Randomization through 3 years
Number of Participants With Disease Progression or Death by Tumor Size (<= 3 cm and > 3 cm) Per Treatment Group	Including local, regional, or distant progression events, or death. Local progression event: occurring in the treated tumor. Regional progression event: occurring in the same part of the body as the treated tumor. Distant progression event: occurring outside the region of the body where the treated tumor is located.	Randomization through 18 months
The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Freedom From Local Progression (FFLP)	The impact of elevated AFP level on time to event endpoints will be evaluated both in terms of the initial AFP level and on-study levels in a Cox proportional hazards model.	Up to 18 months
The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Progression-free Survival (PFS)	The impact of elevated AFP level on time to event endpoints will be evaluated both in terms of the initial AFP level and on-study levels in a Cox proportional hazards model.	Up to 18 months
The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Extra Hepatic PFS	The impact of elevated AFP level on time to event endpoints: FFLP, PFS, extra hepatic PFS and OS will be evaluated both in terms of the initial AFP level and on-study levels in a Cox proportional hazards model.	Up to 18 months
The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Overall Survival (OS)	The impact of elevated AFP level on time to event endpoints will be evaluated both in terms of the initial AFP level and on-study levels in a Cox proportional hazards model.	Up to 18 months

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Daniel Chang, MD, Stanford University; Principal Investigator: Erqi Liu Pollom, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2016
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: April 5, 2016
• First Submitted That Met QC Criteria: May 2, 2016
• First Posted (Estimated): May 4, 2016

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Recurrence; Antineoplastic Agents; Ethiodized Oil
• Other Study ID Numbers: IRB-35937; P30CA124435 (U.S. NIH Grant/Contract); NCI-2016-00418 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); HEP0052 (Other Identifier: OnCore ID)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO