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

Phase 3

Terminated

• Conditions: Hepatocellular Carcinoma; HCC
• Interventions: Radiation: Stereotactic Body Radiation Therapy (SBRT); Procedure: Trans-Arterial Chemoembolization (TACE); Drug: Doxorubin

• Registration Number: NCT03960008
• Lead Sponsor: Lahey Clinic

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.

Study Timeline

• Study First Submitted: 2019-04-30
• Study First Submitted QC: 2019-05-21
• Study First Posted: 2019-05-22
• Study Start: 2020-03-01
• Primary Completion: 2024-02-28
• Study Completion: 2024-02-28
• Results First Submitted: 2024-04-04
• Status Verified: 2024-08
• Results First Submitted QC: 2024-08-02
• Last Update Submitted: 2024-08-02
• Results First Posted: 2024-08-28
• Last Update Posted: 2024-08-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 9

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.

Read More

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).

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Stereotactic Body Radiation Therapy (SBRT)	Stereotactic Body Radiation Therapy (SBRT)	Radiation Therapy
Trans-Arterial Chemoembolization (TACE)	Trans-Arterial Chemoembolization (TACE)	Procedure/Surgery - Chemoembolization Drug: Doxorubin
Trans-Arterial Chemoembolization (TACE)	Doxorubin	Procedure/Surgery - Chemoembolization Drug: Doxorubin

Primary Outcome Measures

Name	Time	Method
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	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.

Secondary Outcome Measures

Name	Time	Method
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	To compare treatment related adverse events between both arms, SBRT and TACE.
Number of Further Interventions	2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment	To compare the number of further interventions between the SBRT and TACE arms.
Rate of Pathological Response of Treated Lesion(s)	Review of pathology report after liver transplant	Complete pathologic response of lesions will be analyzed on the explant liver specimen after liver transplant. The pathology note will be consulted.
To Assess Quality of Life by Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) Questionnaire	Baseline, during treatment, 2 months post-treatment, 5 months post-treatment, every 3 months until 24 months post treatment	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.
To Assess 90 Day Post-transplant Mortality	Survival status to be captured 90 days post-transplantation (+/- 2 weeks)	Will assess the mortality of post-transplant patients between the two arms.
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	Response of treated lesions will be analyzed at protocol specified time frames. The response rate between both treatment arms will be compared.
To Assess Over Survival	Baseline, during treatment, 2 months post-treatment, 5 months post-treatment, every 3 months until 24 months post treatment	Overall survival will be compared in both arms at protocol specified time frames.
To Assess 90 Day Post-transplant Morbidity	Disease status to be captured 90 days post-transplantation (+/- 2 weeks)	Compare the morbidity at 90 days post transplant between both arms.

Trial Locations

Locations (5)

Princess Margaret Hospital, UHN; 🇨🇦 Toronto, Ontario, Canada

Mayo Clinic; 🇺🇸 Rochester, Minnesota, 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