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

• ClinicalTrials.gov Identifier: NCT01381211
• Recruitment Status: Terminated
• First Posted: June 27, 2011
• Last Update Posted: December 15, 2022
• Sponsor: University Hospital, Ghent
• Information provided by (Responsible Party): University Hospital, Ghent

Tracking Information

• First Submitted Date: June 14, 2011
• First Posted Date: June 27, 2011
• Last Update Posted Date: December 15, 2022
• Actual Study Start Date: September 2011
• Actual Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 22, 2011)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 13, 2022)

• 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.
• Survival of patients dedicated to either treatment arm. [ Time Frame: Patients are followed for up to 2 years. ]
  Survival of patients is followed.
• 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).
• 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.
• 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.
• 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.

Original Secondary Outcome Measures (submitted: June 22, 2011)

• 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.
• Survival of patients dedicated to either treatment arm. [ Time Frame: Patients are followed for up to 2 years. ]
  Survival of patients is followed.
• Quality of life [ 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 Organisation for Research and Treatment of Cancer Quality of Life (EORTC-QLQ30).
• 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 respons, partial response, stable disease.
• 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.
• 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Transarterial RAdioembolization Versus ChemoEmbolization for the Treatment of Hepatocellular Carcinoma (HCC)
• Official Title: Transarterial RAdioembolization Versus ChemoEmbolization for the Treatment of HCC: A Multicenter Randomized Controlled Trial (TRACE Trial)

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hepatocellular Carcinoma

Intervention

• Drug: TACE-DEB
  Transcatheter arterial chemoembolization (TACE) is performed with drug eluting beads (DEB), polyvinyl alcohol-based microspheres loaded with the chemotherapeutic agent doxorubicin.
• Drug: 90Y-RE
  Glass Yttrium-90 microspheres (TheraSphere®; MDS Nordion Inc.) will be used

Study Arms

• Active Comparator: Yttrium-90 radioembolization (90Y-RE)
  Intervention: Drug: 90Y-RE
• 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.
  Intervention: Drug: TACE-DEB

Publications *

• Dhondt E, Lambert B, Hermie L, Huyck L, Vanlangenhove P, Geerts A, Verhelst X, Aerts M, Vanlander A, Berrevoet F, Troisi RI, Van Vlierberghe H, Defreyne L. 90Y Radioembolization versus Drug-eluting Bead Chemoembolization for Unresectable Hepatocellular Carcinoma: Results from the TRACE Phase II Randomized Controlled Trial. Radiology. 2022 Jun;303(3):699-710. doi: 10.1148/radiol.211806. Epub 2022 Mar 8.
• Seinstra BA, Defreyne L, Lambert B, Lam MG, Verkooijen HM, van Erpecum KJ, van Hoek B, van Erkel AR, Coenraad MJ, Al Younis I, van Vlierberghe H, van den Bosch MA. Transarterial radioembolization versus chemoembolization for the treatment of hepatocellular carcinoma (TRACE): study protocol for a randomized controlled trial. Trials. 2012 Aug 23;13:144. doi: 10.1186/1745-6215-13-144.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 13, 2022): 72
• Original Estimated Enrollment (submitted: June 22, 2011): 140
• Actual Study Completion Date: March 2020
• Actual Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium
• Removed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT01381211
• Other Study ID Numbers: 2011/050
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: University Hospital, Ghent
• Original Responsible Party: Prof. dr. L. Defreyne, University Hospital Ghent
• Current Study Sponsor: University Hospital, Ghent
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: University Hospital, Ghent
• Verification Date: September 2019