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

Hepatocellular Carcinoma Clinical Trial

— SBRTvsTACE  

Official title:

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03960008
• Other study ID #: 20193013
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 1, 2020
• Est. completion date: March 2024

Study information

• Verified date: February 2024
• Source: Lahey Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 196
• Est. completion date: March 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• HCC
• Hepatocellular Carcinoma

Intervention

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.

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

Drug:
• Doxorubin
This procedure will be completed with 2 vials of drug eluting beads each loaded with 50 mg of Doxorubin.

Locations

Country	Name	City	State
Canada	Princess Margaret Hospital, UHN	Toronto	Ontario
United States	Lahey Hospital & Medical Center	Burlington	Massachusetts
United States	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Lahey Clinic	Merit Medical Systems, Inc., Varian Medical Systems

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		1 year post treatment
Secondary	To compare participants with treatment-related adverse events as assessed by CTCAE v5.0		At each treatment, 2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment
Secondary	Number of further interventions		2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment
Secondary	Rate of pathological response of treated lesion(s)		Review of pathology report after liver transplant
Secondary	Rate of radiological response of treated lesion(s)		Baseline, 2 months post-treatment, 5 months post-treatment, every 3 months thereafter until 2 years post treatment
Secondary	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
Secondary	To assess over survival		Baseline, during treatment, 2 months post-treatment, 5 months post-treatment, every 3 months until 24 months post treatment
Secondary	To assess 90 day Post-transplant morbidity		Disease status to be captured 90 days post-transplantation (+/- 2 weeks)
Secondary	To assess 90 day Post-transplant mortality		Survival status to be captured 90 days post-transplantation (+/- 2 weeks)