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

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.

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 Overview

• Status: Completed
• Conditions: HCC; Hepatocellular Carcinoma
• Intervention / Treatment: Radiation: Stereotactic Body Radiation Therapy (SBRT); Drug: Doxorubin; Procedure: Trans-Arterial Chemoembolization (TACE)

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 Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital & Medical Center

Participation Criteria

Eligibility Criteria

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

Description

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.

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
Other: 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 Names: Radiation Therapy
Other: Arm B; Trans-Arterial Chemoembolization (TACE) Drug: Doxorubin	Drug: Doxorubin; This procedure will be completed with 2 vials of drug eluting beads each loaded with 50 mg of Doxorubin.; Other Names: Doxorubin bead therapy; 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 Names: Chemoembolization

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom From Progression Over Time	Time from SBRT and TACE intervention to progression was tracked for subject receiving protocol intervention. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesion.	3, 6 and 12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity To Compare Participants With Treatment-related Adverse Events as Assessed by CTCAE	Grade 3 or greater toxicity with treatment-related adverse events was tracked at protocol specific time points. Grading of events was according to CTCAE.	At each treatment, 2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment
Number of Participants Who Require Further Interventions Prior to Liver Transplant	Each patient on each arm was followed to see how if further treatment interventions were needed prior to liver transplant. This outcome summarizes the number of participants who needed further treatment.	2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment
Pathologic Response of Treated Lesion(s)	Pathologic complete response was recorded for patients in both arms after completion of liver transplant. Explanted liver was reviewed by the pathologist to determine if residual tumor was identified.	At time of liver transplant
Radiologic Response of Treat Lesion(s)	Number of patients with a radiographical response to treatment.The status of each treated tumor/target lesion was assessed by MRI or CT scan and classified as progression if there was tumor growth (excluding growth due to biloma or abscess formation), residual or new enhancement of the ablated tumor (excluding benign peri-ablational enhancement), or contiguous viable tumor as determined by mRECIST Criteria.	Baseline, 3 months post-treatment, 6 months post-treatment, every 3 months thereafter until 2 years post treatment
Quality of Life - Questionnaires Include PIQ-6 and SF-36v2 Health Survey	Quality of life was assessed with Short Form 36 Health Survey (SF-36v2®) and Pain Impact Questionnaire (PIQ-6TM) Health Survey. Data was stored and scored with Pro CoRE 2.0 Smart Measurement® System. Scores were analyzed at three time points, baseline-before the first treatment, acute response-2 weeks post the first treatment, and long term response - 6 months after the first treatment. The PIQ-6 Pain Impact Questionnaire measures how a subject's pain affects every day activities. The SF-36v2 Health Survey measures functional health and well-being from the subject's point of view. The survey's scores range from 0-100, with 0 having the most disability and a score of 100 being equivalent to no disability.	Baseline, 2 weeks post-treatment, 6 months post-treatment

Collaborators and Investigators

• Sponsor: Lahey Clinic
• Collaborators: Varian Medical Systems
• Investigators: Principal Investigator: Francis W Nugent, MD, Lahey Hospital & Medical Center

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): October 1, 2021
• Study Completion (Actual): October 1, 2021

Study Registration Dates

• First Submitted: June 23, 2014
• First Submitted That Met QC Criteria: July 7, 2014
• First Posted (Estimated): July 8, 2014

Study Record Updates

• Last Update Posted (Actual): March 5, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Bridge to transplant; Hepatocellular carcinoma (HCC); stereotactic body radiation therapy (SBRT); Orthotopic liver transplant; trans-arterial chemoembolization (TACE)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: LCID 2014-026

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• 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