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

A Randomized Multi-Center Phase III Study of Individualized Stereotactic Body Radiation Therapy (SBRT) Versus Trans-Arterial Chemoembolization (TACE) 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 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 liver transplantation in subjects with HCC.

Study Overview

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

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. For patients undergoing local regional therapy as a bridge to transplantation, trans-arterial chemoembolization (TACE) is the most commonly utilized treatment. However, the best modality for patients undergoing treatment as a bridge to transplantation is unclear. A newer strategy for the treatment of HCC is stereotactic body radiation therapy (SBRT). This study will compare SBRT to TACE as a bridging strategy for patients with HCC undergoing liver transplantation.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X6
      • Princess Margaret Hospital, UHN
• United States
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital & Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43202
      • The Ohio State University Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Subjects with HCC are eligible for this trial. HCC is defined as having at least one of the following:

   • Biopsy proven HCC or:
   • A discrete hepatic tumor(s) as defined by the Barcelona (29) criteria for cirrhotic subjects, ≥2cm with arterial hypervascularity and venous or delayed phase washout on CT or MRI.
2. Subjects are liver transplant candidates (actively awaiting organ transplant per transplant services in documentation), or, potential liver transplant candidates (at the discretion of the liver team and/or Principal Investigator) advised by liver transplant services as needing local treatment prior to liver transplant evaluation.
3. Subjects must be within UCSF criteria (one solitary tumor smaller than 6.5 cm, or patients having 3 or fewer nodules, with the largest lesion being smaller than 4.5 cm or having a total tumor diameter less than 8.5 cm without vascular invasion) and eligible for potential liver transplant.
4. Subjects must be eligible per standard of care for either TACE or SBRT procedures.
5. Subjects must have a life expectancy of at least 12 weeks.
6. Subjects must be 18 years of age or older. Adult subjects of all ages, both sexes and all races will be included in this study.
7. Subjects must sign an informed consent form approved for this purpose by the Institutional Review Board (IRB) of record .
8. Subjects must have a Child-Turcotte-Pugh (CTP) score ≤8.

9. 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 < 3.0 mg/dl (in the absence of obstruction or pre-existing disease of the biliary tract, e.g. primary sclerosing cholangitis).
10. Patients uninvolved liver volume will be estimated and must be > 700ml.
11. Patients must have a Zubrod performance status of ≤2.

Exclusion Criteria:

1. Subjects in a "special category" designated by the Public Health Service, Including subjects younger than 18, pregnant women, and prisoners.
2. Refractory ascites that requires paracentesis for management.
3. Known allergy to intravenous iodinated contrast agents unresponsive to prednisone pre-treatment.
4. History of prior radiation to the liver.
5. Evidence of metastatic disease.
6. Presence of a Trans-jugular intra-hepatic porto-systemic shunt (TIPS).

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: Stereotactic Body Radiation Therapy (SBRT); Radiation Therapy	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: Trans-Arterial Chemoembolization (TACE); Procedure/Surgery - Chemoembolization 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 Names: Chemoembolization; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Compare the Duration of Disease Control in Treated Lesions When Utilizing SBRT Versus TACE as a Bridging Strategy for Patients With HCC Eligible for Liver Transplantation	To compare whether or not there was disease present in treated lesions in both the SBRT and TACE arms in patients eligible for liver transplant at 1 year post treatment.	1 year post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Compare Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0	To compare treatment related adverse events between both arms, SBRT and TACE.	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 Further Interventions	To compare the number of further interventions between the SBRT and TACE arms.	2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment
Rate of Pathological Response of Treated Lesion(s)	Complete pathologic response of lesions will be analyzed on the explant liver specimen after liver transplant. The pathology note will be consulted.	Review of pathology report after liver transplant
Rate of Radiological Response of Treated Lesion(s)	Response of treated lesions will be analyzed at protocol specified time frames. The response rate between both treatment arms will be compared.	Baseline, 2 months post-treatment, 5 months post-treatment, every 3 months thereafter until 2 years post treatment
To Assess Quality of Life by Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) Questionnaire	A 45-item self-report instrument to measure health-related quality of life (HRQL) in patients with hepatobiliary cancers and is one of the most widely-used instruments in this clinical area. The FACT-Hep consists of the 27-item FACT-G, assesses HRQL, and the 18-item Hepatobiliary Subscale (HS), assesses disease-specific issues such as pain, appetite, and cramping. The FACT-G evaluates physical well-being, social/family well-being, emotional well-being, and functional well-being. Sections have a 7-day reference period and are scored from 0-4 ("not at all" to "very much"), with higher scores indicating better HRQL. Score ranges are 0-28 for physical well-being, 0-28 for social/family well-being, 0-24 for emotional well-being, 0-28 for functional well-being, and 0-72 for the HS. All subscale scores from the FACT-G and HS can be summed together to create a total FACT-Hep score, with a possible range of 0-180. The FACT-Hep takes approximately 10 minutes to complete.	Baseline, during treatment, 2 months post-treatment, 5 months post-treatment, every 3 months until 24 months post treatment
To Assess Over Survival	Overall survival will be compared in both arms at protocol specified time frames.	Baseline, during treatment, 2 months post-treatment, 5 months post-treatment, every 3 months until 24 months post treatment
To Assess 90 Day Post-transplant Morbidity	Compare the morbidity at 90 days post transplant between both arms.	Disease status to be captured 90 days post-transplantation (+/- 2 weeks)
To Assess 90 Day Post-transplant Mortality	Will assess the mortality of post-transplant patients between the two arms.	Survival status to be captured 90 days post-transplantation (+/- 2 weeks)

Collaborators and Investigators

• Sponsor: Lahey Clinic
• Collaborators: Varian Medical Systems; Merit Medical Systems, Inc.
• Investigators: Principal Investigator: Corrine Zarwan, MD, Lahey Hospital & Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2020
• Primary Completion (Actual): February 28, 2024
• Study Completion (Actual): February 28, 2024

Study Registration Dates

• First Submitted: April 30, 2019
• First Submitted That Met QC Criteria: May 21, 2019
• First Posted (Actual): May 22, 2019

Study Record Updates

• Last Update Posted (Actual): August 28, 2024
• Last Update Submitted That Met QC Criteria: August 2, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Liver transplant; Hepatocellular Carcinoma (HCC); Bridge to transplant; Stereotactic body radiation therapy (SBRT); 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: 20193013

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.: Yes