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

Hepatocellular Carcinoma Clinical Trial

— SBRTvsTACE  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02182687
• Other study ID #: LCID 2014-026
• Status: Completed
• Phase: Phase 2
• Start date: June 2014
• Est. completion date: October 2021

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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: October 2021
• Est. primary completion date: October 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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
United States	Lahey Hospital & Medical Center	Burlington	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Lahey Clinic	Varian Medical Systems

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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