Clinical trial NCT02762266: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Child-Pugh Class A
Child-Pugh Class B
Recurrent Hepatocellular Carcinoma
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2016-05-04
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With a Local Progression Event
timeFrame: Up to 12 months
Secondary outcomes:
measure: Comparison of Median Freedom From Extra Hepatic Progression
timeFrame: Up to 16 weeks
measure: Median Extra Hepatic PFS for Patients With Tumors Smaller Than 3 cm and Greater Than 3 cm Per Treatment Group
timeFrame: At 18 months
measure: Median FFLP for Patients With Tumors Smaller Than 3 cm and With Tumors Greater Than 3 cm Per Treatment Group
timeFrame: At 18 months
measure: Median OS
timeFrame: Time from randomization until death from any cause, assessed up to 3 years
measure: Median OS for Patients With Tumors Smaller Than 3 cm and Greater Than 3 cm Per Treatment Group
timeFrame: At 18 months
measure: Number of Participants With Disease Progression or Death
timeFrame: Randomization through 3 years
measure: Number of Participants With Disease Progression or Death by Tumor Size (<= 3 cm and > 3 cm) Per Treatment Group
timeFrame: Randomization through 18 months
measure: The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Freedom From Local Progression (FFLP)
timeFrame: Up to 18 months
measure: The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Progression-free Survival (PFS)
timeFrame: Up to 18 months
measure: The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Extra Hepatic PFS
timeFrame: Up to 18 months
measure: The Impact of Elevated Serum Alpha-Fetoprotein Level (AFP) on Overall Survival (OS)
timeFrame: Up to 18 months
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University, School of Medicine
state: California
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
Study officials:
affiliation: Stanford University
name: Erqi Liu Pollom, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Daniel Chang, MD
role: PRINCIPAL_INVESTIGATOR
References: