Transarterial RAdioembolization Versus ChemoEmbolization for the Treatment of Hepatocellular Carcinoma (HCC) (TRACE)

December 13, 2022 updated by: University Hospital, Ghent

Transarterial RAdioembolization Versus ChemoEmbolization for the Treatment of HCC: A Multicenter Randomized Controlled Trial (TRACE Trial)

Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver that accounts for an important health problem worldwide. In only 10% - 15% of all patients with HCC, tumors are considered resectable at presentation. In contrast to metastatic liver disease, there is no role for systemic chemotherapy in the treatment of HCC. Today only evidence is available for Sorafenib, a tyrosine kinase inhibiting agent. The arsenal of non-surgical therapies can roughly be divided into local ablative, transarterial and systemic therapies. In well selected patients, local ablative therapy can offer favorable long term results.

For patients with disease confined to the liver, but locally more advanced, transarterial treatment modalities are proposed. These therapies exploit the dual blood supply to the liver. HCC derives its blood supply almost entirely from the hepatic artery, while liver parenchyma derives > 75% of its blood supply from the portal vein. Antitumoral agents, such as cytotoxic drugs or radionuclides, can be delivered in close proximity of the tumor.

Examples of transarterial therapies are: transarterial chemoembolization (TACE), bland transarterial embolization (TAE), transarterial chemoembolization with drug eluting beads (TACE-DEB) and transarterial radioembolization with Iodine-131 or Yttrium-90.

TACE is currently the gold standard for treatment of patients with intermediate stage HCC, with a reported median survival of around 17 months. A novel development in the TACE treatment for HCC is the drug-eluting bead (DEB). Recently performed small clinical trials reported the efficacy of DEBs in the treatment of intermediate stage HCC, which is substantially higher compared to conventional TACE.

Yttrium-90 radioembolization (90Y-RE) is a relatively recently developed technique which implements transarterial administration of minimally embolic microspheres loaded with Yttrium-90, a β-emitting isotope, delivering selective internal radiation to the tumor.

In this study the investigators want to prospectively compare TACE-DEB and 90Y-RE, two novel treatments that both have theoretical and/or proven advantages compared to the use of conventional TACE, in patients with intermediate stage HCC.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

72

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Ghent, Belgium, 9000
        • University Hospital Ghent

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Written informed consent.
  • The diagnosis HCC is confirmed by typical appearance on imaging or cytohistological evaluation (liver biopsy).
  • Accurate staging:

MRI of the liver CT-scan of the abdomen and thorax bone scintigraphy, only in case of clinical symptoms suggestive of skeletal metastases.

Exclusion Criteria:

  • Hypersensitivity to doxorubicin
  • Pregnancy or breastfeeding
  • Age under 18 years
  • Child-Pugh score >B7
  • ECOG performance status (PST) > 1
  • Bilirubin > 2.6 mg/dl
  • AST/ALT >5x upper limit of normal (ULN)
  • >50% of liver involvement
  • Main portal vein (right, left or common trunk) thrombosis
  • Extra-hepatic disease
  • Previous treatment of study target lesions
  • 99mTc-labelled macroaggregated albumin (99mTc-MAA) scintigraphy shows lack of MAA uptake in tumor (photopenic lesion)
  • Activity > 610 MBq and activity reduction would imply a liver target dose > 80 Gy
  • patients who are declared incompetent or suffering from physic disorders that make a comprehensive judgement impossible, such as psychosis.
  • Unmanageable intolerance for contrast medium
  • Life expectancy < 3 months or otherwise impossible follow-up
  • Inadequate bone marrow, liver and/or renal function
  • other contraindications to hepatic embolization procedures.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Yttrium-90 radioembolization (90Y-RE)
Drug: 90Y-RE
Glass Yttrium-90 microspheres (TheraSphere®; MDS Nordion Inc.) will be used
Active Comparator: Transarterial chemoembolization with drug eluting beads
Transarterial chemoembolization is performed with drug eluting beads, polyvinyl alcohol-based microspheres (DC Beads, Biocompatibles) loaded with the chemotherapeutic agent doxorubicin.
Drug: TACE-DEB
Transcatheter arterial chemoembolization (TACE) is performed with drug eluting beads (DEB), polyvinyl alcohol-based microspheres loaded with the chemotherapeutic agent doxorubicin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Progression (TTP).
Time Frame: Patients will be followed over a 2 years period.
Tumor progression is defined according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) response evaluation criteria. The mRECIST evaluation criteria define progressive disease by the implication of target lesions response, non-target lesions response and the occurrence of new lesions.
Patients will be followed over a 2 years period.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Local Progression (TLP).
Time Frame: Since start of treatment untill local tumor progression with a maximum of 2 years follow up.
In both study arms, treatment is done selectively for the lesions within the perfusion area (may be lobar, segmental or subsegmental), as visualized with Cone-Beam CT prior to intervention.
Since start of treatment untill local tumor progression with a maximum of 2 years follow up.
Survival of patients dedicated to either treatment arm.
Time Frame: Patients are followed for up to 2 years.
Survival of patients is followed.
Patients are followed for up to 2 years.
Quality of life EQ5D
Time Frame: Before treatment and after treatment on a 3 monthly interval during 2 years.
Quality of life as measured with The Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) scale, The Short Form (36) Health Survey, EuroQol Group 5-Dimension Self-Report Questionnaire score (EQ5D) and European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ30).
Before treatment and after treatment on a 3 monthly interval during 2 years.
Tumor response to therapy according to mRECIST criteria
Time Frame: Before treatment and after treatment on a 3 monthly interval during 2 years.
European Association for the Study of the Liver (EASL) response will be obtained based on the following: complete response, partial response, stable disease.
Before treatment and after treatment on a 3 monthly interval during 2 years.
Treatment-related costs.
Time Frame: After follow up of 2 year.
Treatment-related costs, in terms of cost of therapy and number of hospitalization days, in these patients.
After follow up of 2 year.
Toxicities and adverse events (recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 3.0)
Time Frame: 6 months following last treatment
The number of patients with AEs, SAEs and SUSARs and the total number of AEs, SAEs and SUSARs in both treatment groups.
6 months following last treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Ghent

Investigators

  • Principal Investigator: Luc Defreyne, MD, PhD, University Hospital, Ghent

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2011

Primary Completion (Actual)

March 1, 2018

Study Completion (Actual)

March 1, 2020

Study Registration Dates

First Submitted

June 14, 2011

First Submitted That Met QC Criteria

June 22, 2011

First Posted (Estimate)

June 27, 2011

Study Record Updates

Last Update Posted (Actual)

December 15, 2022

Last Update Submitted That Met QC Criteria

December 13, 2022

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2011/050

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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