Clinical trial NCT03960008: Stereotactic Body Radiation Therapy (SBRT) vs Trans-Arterial Chemoembolization (TACE) as Bridge to Transplant
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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hepatocellular Carcinoma
HCC
Keywords: Hepatocellular Carcinoma (HCC)
Liver transplant
Bridge to transplant
Stereotactic body radiation therapy (SBRT)
Trans-arterial chemoembolization (TACE)
Lead sponsor: Lahey Clinic
Sponsor class: OTHER
Collaborators: name: Varian Medical Systems
name: Merit Medical Systems, Inc.
First posted: 2019-05-22
Enrollment: 9
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 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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: 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
timeFrame: 1 year post treatment
Secondary outcomes:
measure: To Compare Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0
timeFrame: At each treatment, 2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment
measure: Number of Further Interventions
timeFrame: 2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment
measure: Rate of Pathological Response of Treated Lesion(s)
timeFrame: Review of pathology report after liver transplant
measure: Rate of Radiological Response of Treated Lesion(s)
timeFrame: Baseline, 2 months post-treatment, 5 months post-treatment, every 3 months thereafter until 2 years post treatment
measure: To Assess Quality of Life by Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) Questionnaire
timeFrame: Baseline, during treatment, 2 months post-treatment, 5 months post-treatment, every 3 months until 24 months post treatment
measure: To Assess Over Survival
timeFrame: Baseline, during treatment, 2 months post-treatment, 5 months post-treatment, every 3 months until 24 months post treatment
measure: To Assess 90 Day Post-transplant Morbidity
timeFrame: Disease status to be captured 90 days post-transplantation (+/- 2 weeks)
measure: To Assess 90 Day Post-transplant Mortality
timeFrame: Survival status to be captured 90 days post-transplantation (+/- 2 weeks)
Other outcomes:
Locations:
city: Burlington
country: United States
facility: Lahey Hospital & Medical Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Toronto
country: Canada
facility: Princess Margaret Hospital, UHN
state: Ontario
Study officials:
affiliation: Lahey Hospital & Medical Center
name: Corrine Zarwan, MD
role: PRINCIPAL_INVESTIGATOR
References: