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

Phase 3

Terminated

Conditions: Child-Pugh Class B
Recurrent Hepatocellular Carcinoma
Child-Pugh Class A

Interventions: Procedure: Transarterial Chemoembolization
Radiation: Stereotactic Body Radiation Therapy
Drug: embolic agent
Drug: lipiodol

Registration Number: NCT02762266

Lead Sponsor: Stanford University

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 13

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (TACE)	embolic agent	Patients undergo TACE.
Arm I (TACE)	Transarterial Chemoembolization	Patients undergo TACE.
Arm II (SBRT)	Stereotactic Body Radiation Therapy	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.
Arm I (TACE)	lipiodol	Patients undergo TACE.

Primary Outcome Measures

Name	Time	Method
Number of Participants With a Local Progression Event	Up to 12 months	Local progression event: occurring in the treated hepatic lesion.

Secondary Outcome Measures

Name	Time	Method
The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Freedom From Local Progression (FFLP)	Up to 18 months	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.
The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Progression-free Survival (PFS)	Up to 18 months	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.
The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Overall Survival (OS)	Up to 18 months	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.
Comparison of Median Freedom From Extra Hepatic Progression	Up to 16 weeks	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.
The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Extra Hepatic PFS	Up to 18 months	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.
Median OS	Time from randomization until death from any cause, assessed up to 3 years	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.
Median Extra Hepatic PFS for Patients With Tumors Smaller Than 3 cm and Greater Than 3 cm Per Treatment Group	At 18 months	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.
Median FFLP for Patients With Tumors Smaller Than 3 cm and With Tumors Greater Than 3 cm Per Treatment Group	At 18 months	FFLP within each subgroup will be summarized by cumulative incidence function estimators adjusted for the competing risk of death or regional or distant progression.
Median OS for Patients With Tumors Smaller Than 3 cm and Greater Than 3 cm Per Treatment Group	At 18 months	Within each subgroup OS will be summarized using Kaplan-Meier curves and medians with 95% confidence intervals calculated using Greenwood's formula.
Number of Participants With Disease Progression or Death	Randomization through 3 years	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.
Number of Participants With Disease Progression or Death by Tumor Size (<= 3 cm and > 3 cm) Per Treatment Group	Randomization through 18 months	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.

Trial Locations

Locations (2): Hokkaido University Hospital
🇯🇵
Sapporo, Hokkaido, Japan
Stanford University, School of Medicine
🇺🇸
Palo Alto, California, United States