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

NCT02182687 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: LCID 2014-026
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Hepatocellular Carcinoma; HCC

Keywords

Hepatocellular carcinoma (HCC); Orthotopic liver transplant; Bridge to transplant; stereotactic body radiation therapy (SBRT); trans-arterial chemoembolization (TACE)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Toxicity To Compare Participants With Treatment-related Adverse Events as Assessed by CTCAE

  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 Participants Who Require Further Interventions Prior to Liver Transplant

  2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment

• Pathologic Response of Treated Lesion(s)

  At time of liver transplant

• Radiologic Response of Treat Lesion(s)

  Baseline, 3 months post-treatment, 6 months post-treatment, every 3 months thereafter until 2 years post treatment

• Quality of Life - Questionnaires Include PIQ-6 and SF-36v2 Health Survey

  Baseline, 2 weeks post-treatment, 6 months post-treatment

Study Arms (2)

Arm A

OTHER

Stereotactic Body Radiation Therapy (SBRT)

Radiation: Stereotactic Body Radiation Therapy (SBRT)

Arm B

OTHER

Trans-Arterial Chemoembolization (TACE) Drug: Doxorubin

Procedure: Trans-Arterial Chemoembolization (TACE); Drug: Doxorubin

Interventions

Stereotactic Body Radiation Therapy (SBRT) RADIATION

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.

Also known as: Radiation Therapy

Arm A

Trans-Arterial Chemoembolization (TACE) PROCEDURE

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.

Also known as: Chemoembolization

Arm B

Doxorubin DRUG

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

Also known as: Doxorubin bead therapy

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lahey Clinic: lead
• Varian Medical Systems: collaborator

Study Sites (1)

Lahey Hospital & Medical Center

Burlington, Massachusetts, 01805, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Radiosurgery; Radiotherapy; Chemoembolization, Therapeutic; Doxorubicin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Embolization, Therapeutic; Hemostatic Techniques; Therapeutic Occlusion; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Limitations and Caveats

One primary limitation was the small, single institution, randomized phase II design. Given the small overall numbers, no definitive judgements can be made. Another potential weakness of the trial was the selection of our primary endpoint. Our primary endpoint was time to residual or progressive cancer in the previously treated lesion(s). A third limitation of this trial was incomplete compliance with QOL questionnaires. Lastly, our QOL measures were performed over a long interval.

Results Point of Contact

• Title: Julia Roache
• Organization: Lahey Hospital & Medical Center

julia.roache@lahey.org

781-744-3055

Study Officials

• Francis W Nugent, MD

  Lahey Hospital & Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2014
• First Posted: July 8, 2014
• Study Start: June 1, 2014
• Primary Completion: October 1, 2021
• Study Completion: October 1, 2021
• Last Updated: March 5, 2024
• Results First Posted: March 5, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)