Clinical trial NCT01381211: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: Intermediate stage hepatocellular carcinoma
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
First posted: 2011-06-27
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Time to Progression (TTP).
timeFrame: Patients will be followed over a 2 years period.
Secondary outcomes:
measure: Time to Local Progression (TLP).
timeFrame: Since start of treatment untill local tumor progression with a maximum of 2 years follow up.
measure: Survival of patients dedicated to either treatment arm.
timeFrame: Patients are followed for up to 2 years.
measure: Quality of life EQ5D
timeFrame: Before treatment and after treatment on a 3 monthly interval during 2 years.
measure: Tumor response to therapy according to mRECIST criteria
timeFrame: Before treatment and after treatment on a 3 monthly interval during 2 years.
measure: Treatment-related costs.
timeFrame: After follow up of 2 year.
measure: Toxicities and adverse events (recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 3.0)
timeFrame: 6 months following last treatment
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: University Hospital Ghent
Study officials:
affiliation: University Hospital, Ghent
name: Luc Defreyne, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.