Stereotactic Body Radiation Therapy (SBRT) Versus Trans-Arterial Chemoembolization (TACE) as Bridge to Liver Transplant (SBRTvsTACE)

• ClinicalTrials.gov Identifier: NCT02182687
• Recruitment Status: Completed
• First Posted: July 8, 2014
• Last Update Posted: December 6, 2021
• Sponsor: Lahey Clinic
• Collaborator: Varian Medical Systems
• Information provided by (Responsible Party): Lahey Clinic

Study Description

Brief Summary:

This study will compare stereotactic body radiation therapy (SBRT) to trans-arterial chemoembolization (TACE) as a bridging strategy for patients with HCC undergoing orthotopic liver transplantation. We propose that SBRT will be associated with longer time intervals between initial treatment and the need for retreatment, compared to TACE, as a "bridge" to orthotopic liver transplantation.

Condition or disease	Intervention/treatment	Phase
Hepatocellular Carcinoma; HCC	Radiation: Stereotactic Body Radiation Therapy (SBRT); Procedure: Trans-Arterial Chemoembolization (TACE); Drug: Doxorubin	Phase 2

Detailed Description:

For patients with hepatocellular carcinoma (HCC) who are waiting for a liver transplant, local treatment of their disease has become the standard of care in an effort to decrease dropout rates and as a means of reducing tumor recurrence after transplantation. However, the best modality for patients undergoing treatment as a bridge to transplantation is unclear. This study will compare stereotactic body radiation therapy (SBRT) to trans-arterial chemoembolization (TACE) as a bridging strategy for patients with HCC undergoing orthotopic liver transplantation. We propose that SBRT will be associated with longer time intervals between initial treatment and the need for retreatment, compared to TACE, as a "bridge" to orthotopic liver transplantation.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Study of Individualized Stereotactic Body Radiation Therapy (SBRT) Versus Trans-Arterial Chemoembolization (TACE) With DEBDOX Beads as a Bridge to Transplant in Hepatocellular Carcinoma.
• Study Start Date: June 2014
• Actual Primary Completion Date: October 2021
• Actual Study Completion Date: October 2021

Arms and Interventions

Arm	Intervention/treatment
Arm A; Stereotactic Body Radiation Therapy (SBRT)	Radiation: Stereotactic Body Radiation Therapy (SBRT); SBRT will be delivered in five total fractions, with at a minimum of one day between any two treatments. The entire treatment must be delivered within 15 total days.; Other Name: Radiation Therapy
Arm B; Trans-Arterial Chemoembolization (TACE) Drug: Doxorubin	Procedure: Trans-Arterial Chemoembolization (TACE); First day will be administered and a second TACE will be administered after 4 weeks and subsequently if imaging is showing disease progression. Following each TACE procedure all patients will remain in hospital for observation.; Other Name: Chemoembolization; Drug: Doxorubin; This procedure will be completed with 2 vials of drug eluting beads each loaded with 50 mg of Doxorubin.; Other Name: Doxorubin bead therapy

Outcome Measures

Primary Outcome Measures :

1. Time to first additional intervention to the treated lesions [ Time Frame: 1 year post treatment ]

Secondary Outcome Measures :

1. Toxicity [ Time Frame: At each treatment, 2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment ]
2. Number of further interventions [ Time Frame: 2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment ]
3. Pathologic response of treated lesion(s) [ Time Frame: After liver transplant ]
4. Radiologic response of treat lesion(s) [ Time Frame: Baseline, 2 months post-treatment, 5 months post-treatment, every 3 months thereafter until 2 years post treatment ]
5. Quality of Life [ Time Frame: Baseline, during treatment, 2 months post-treatment, 5 months post-treatment, every 3 months until 24 months post treatment ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria

• Patients with hepatocellular carcinoma are eligible for this trial.

Hepatocellular carcinoma is defined as having at least one of the following:

Biopsy proven hepatocellular carcinoma (HCC); or A discrete hepatic tumor(s) as defined by the Barcelona (29) criteria for cirrhotic patients, >2cm with arterial hypervascularity and venous or delayed phase washout on CT or MRI.

• Patient is within Milan Criteria and "listed" for orthotopic liver transplantation.
• Patients must have a Zubrod performance status of ≤2.
• Patients must have a life expectancy of at least 12 weeks.
• Patients must be 18 years of age or older. Adult patients of all ages, both sexes and all races will be included in this study.
• Patients must be Child-Turcotte-Pugh (CTP) Class A or Class B (≤ 7).
• Female patients within reproductive years may not be, nor become, pregnant during participation in this study. Both male and female patients within reproductive years must agree to use an effective contraceptive method during treatment. Women of childbearing age will be required to undergo a urine or serum pregnancy test to ensure they are not pregnant.
• Patients must have adequate organ function within 2 weeks of enrollment. Bone marrow: Platelets ≥30,000/mm3 Renal: BUN ≤40 mg/dl; creatinine ≤2.0 mg/dl Hepatic: INR ≤ 1.5 or correctable by Vitamin K, unless anti- coagulated for another medical reason Bilirubin < 3 mg/dl (in the absence of obstruction or pre-existing disease of the biliary tract, e.g. primary sclerosing cholangitis) Patients uninvolved liver volume will be estimated and must be > 700ml.
• Patients must sign an informed consent form approved for this purpose by the Institutional Review Board (IRB) of the Lahey Hospital and Medical Center indicating that they are aware of the investigational aspects of the treatment and the potential risks.

Exclusion Criteria

• Patients in a "special category" designated the Public Health Service, including patients younger than 18, pregnant women, and prisoners.
• Refractory ascites or ascites that requires paracentesis for management.
• Patients with a solitary lesion greater than 5.0cm in size or more than 2 discrete lesions the largest greater than 3.0 cm in size.
• Known allergy to intravenous iodinated contrast agents unresponsive to prednisone pre-treatment.

Contacts and Locations

Locations

United States, Massachusetts

Lahey Hospital & Medical Center

Burlington, Massachusetts, United States, 01805

Sponsors and Collaborators

Lahey Clinic

Varian Medical Systems

Investigators

• Principal Investigator: Francis W Nugent, MD; Lahey Hospital & Medical Center

More Information

• Responsible Party: Lahey Clinic
• ClinicalTrials.gov Identifier: NCT02182687
• Other Study ID Numbers: LCID 2014-026
• First Posted: July 8, 2014
• Last Update Posted: December 6, 2021
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Lahey Clinic:

Hepatocellular carcinoma (HCC); Orthotopic liver transplant; Bridge to transplant; stereotactic body radiation therapy (SBRT); trans-arterial chemoembolization (TACE)

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; Doxorubicin; Liposomal doxorubicin; Antibiotics, Antineoplastic; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action