Neoplasms

All Conditions

Digestive System Diseases

Symptoms and General Pathology

Carcinoma

Carcinoma, Hepatocellular

Recurrence

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Anti-Infective Agents

Central Nervous System Depressants

Coagulants

Chlorotrianisene

Liver Extracts

Ethanol

Gelatin Sponge, Absorbable

Ethiodized Oil

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.

Stereotactic Body Radiation Therapy

Transarterial Chemoembolization

. Acceptable embolic agents include:

* Gelatin sponge (gelfoam)
* Polyvinyl alcohol (PVA) particles
* Microspheres / Embolic beads

embolic agent

lipiodol

Erqi Liu Pollom, MD

Daniel Chang, MD

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.

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.

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

Local progression event: occurring in the treated hepatic lesion.

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.

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.

FFLP within each subgroup will be summarized by cumulative incidence function estimators adjusted for the competing risk of death or regional or distant progression.

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.

Within each subgroup OS will be summarized using Kaplan-Meier curves and medians with 95% confidence intervals calculated using Greenwood's formula.

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.

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 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.

National Cancer Institute (NCI)

Stanford University

Associate Professor of Radiation Oncology (Radiation Therapy)

Patients undergo TACE using an embolic agent.

Transarterial Chemoembolization (TACE)

Stereotactic Body Radiation Therapy (SBRT)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Japan

Region of Enrollment

Elevated Serum Alpha-Fetoprotein (AFP)

This study did not enroll the planned number of participants and did not meet the protocol-prespecified threshold for statistical significance.

Erqi Pollom, MD

Number of Participants With a Local Progression Event

Comparison of Median Freedom From Extra Hepatic Progression

Median Extra Hepatic PFS for Patients With Tumors Smaller Than 3 cm and Greater Than 3 cm Per Treatment Group

Median FFLP for Patients With Tumors Smaller Than 3 cm and With Tumors Greater Than 3 cm Per Treatment Group

Median OS

Median OS for Patients With Tumors Smaller Than 3 cm and Greater Than 3 cm Per Treatment Group

Number of Participants With Disease Progression or Death

<= 3 cm

> 3 cm

Number of Participants With Disease Progression or Death by Tumor Size (<= 3 cm and > 3 cm) Per Treatment Group

The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Freedom From Local Progression (FFLP)

The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Progression-free Survival (PFS)

The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Extra Hepatic PFS

The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Overall Survival (OS)

Patients undergo TACE using an embolic agent (gelatin sponge \[gelfoam\], polyvinyl alcohol particles, or embolic beads).

Patients undergo image-guided SBRT (3 fractions within 1 week or 5 fractions within 2 weeks).

Spots Global Cancer Trial Database for embolic agent