Clinical trial NCT01676194: Transarterial Chemoembolization Prior to Transplantation for Hepatocellular Carcinoma
Official title: Efficacy of Transarterial Chemoembolization With DC-BeadsR Prior to Liver Transplantation for Hepatocellular Carcinoma on Patient Survival : A Prosepctive Multicentre and Randomized Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hepatocellular Carcinoma
Keywords: Transarterial Chemoembolization
Liver transplantation
Hepatocellular carcinoma
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2012-08-30
Enrollment: 7
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: The hope to treat more patients with hepatocellular carcinoma successfully is however tempered by the shortage of donors leading to an increasing waiting time for liver transplantation (LT). Intention-to-treat analysis have showed that the reported excellent long-term outcome is curtailed and significantly hampered by the growing incidence of patients who must be removed from the waiting list because of tumor progression. A way to face with this issue is to treat hepatocellular carcinoma prior to LT. Among therapeutic options to impede tumor progression, Transarterial Chemoembolization (TACE) is the most common modality used. While there are many studies concerning TACE in this setting, none are controlled studies and thus there is no firm evidence concerning its efficacy in reducing drop-out or increasing survival. Moreover TACE may induce risks (liver failure, arterial complications...) while waiting for LT. Most of the available data have been based upon analysis of patients who received a transplant and have not included patients who were eligible for LT but died, or showed progression, before it could be performed. Therefore, studies conducted on an intention-to-treat basis are needed to clarify the benefit and the risks of TACE prior to LT in patients with hepatocellular carcinoma.

Detailed description: * Multicentre, prospective, randomized, 2 parallel group study
* Preoperative evaluation of hepatocellular carcinoma in recipients: Tumor diagnosis will be mainly based upon EASL guidelines. HCCs will be classified according to UCSF criteria (size, number of nodules). Clinical and biological status will be updated every 3 month.
* Pre-transplant treatment:

TACE group: An emulsion of Lipiodol and a cytotoxic drug (50mg/m2 of doxorubicin) will be injected as selectively as possible. Then, an embolic agent will be used to assure stop of flow. The first injection will be performed within 10 days following enlisting and repeated every 8 weeks until LT (only if hypervascularized vital tumor tissue is again visible on CT Scan and if liver function remains within Child A stage) or until complete response. Clinical/biological follow-up will be done once a month.

Control group (no treatment until LT): clinical/biological follow-up and CT-scan every 3 month.

This prospective, multicentric, and randomized study may allow investigators to show that TACE with DC-BeadsR can significantly increase intention to treat survival of patients transplanted for HCC. We also expect that this result will be associated with less recurrence of the cancer after transplantation.

Obviously, we expect that the beneficial effect of TACE will be associated with a acceptable rate of complication related to the procedure.

* Pathologic examination: In all patients in whom LT will be performed, the diagnosis of hepatocellular carcinoma will be confirmed by a histological examination of the explanted liver.
* Dropout criteria: Patients with progression but still meeting the transplant criteria will be maintained in their respective group. Patients with progression over the transplant criteria will be excluded from the waiting list and censored.

Eligibility criteria: Inclusion Criteria:

* Adult patients \>18 years
* With well compensated cirrhosis and hepatocellular carcinoma meeting UCSF criteria
* Without general contraindication to LT
* Written informed consent.

Exclusion Criteria:

* Patients that already had TACE
* Or other local treatment for HCC
* Or neoadjuvant systemic chemotherapy
* Or planned living donor
* Or non arterialized lesion(s)
* Or Contraindication to DC-BeadsR
* Or allergy to contrast agents
* Or contraindication to Doxorubicin.

Primary outcomes:
measure: Survival
timeFrame: 3 years
Secondary outcomes:
measure: Dropout rate
timeFrame: 3 years
measure: Post-transplantation survival rate
timeFrame: 3 years
measure: Allograft survival
timeFrame: 3 years
measure: Time to dropout
timeFrame: 3 years
measure: Recurrence rate
timeFrame: 3 years
measure: TACE-induced complications (local and general)
timeFrame: 3 years
measure: Contrast agent - induced complications
timeFrame: 3 years
measure: Doxorubicin-induced complications
timeFrame: 3 years
measure: Efficacy of TACE
timeFrame: 3 years
Other outcomes:
Locations:
city: Créteil
country: France
facility: Hôpital Henri Mondor - Assistance Publique-Hôpitaux de Paris
city: Grenoble
country: France
facility: Hôpital Michalon, CHU de Grenoble
city: Lille
country: France
facility: Hôpital Claude Huriez, CHU de Lille
city: Lyon
country: France
facility: Hôpital de la Croix Rousse, HCL, Lyon
city: Paris
country: France
facility: Hôpital Saint-Antoine / APHP
city: Rennes
country: France
facility: Hôpital Pontchaillou
city: Tours
country: France
facility: Hôpital Trousseau, CHU de Tours
Study officials:
affiliation: Service de Chirurgie Digestive - Transplantation Hépatique / Hôpital Henri Mondor - Assistance Publique-Hôpitaux de Paris / Faculté de Médecine - Université Paris-Est
name: Philippe COMPAGNON, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Service de Chirurgie Hépato-biliaire et Digestive, Transplantation Hépatique / CHU de Rennes / Université de Rennes 1
name: Karim BOUDJEMA, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Service de Pharmacologie et CIC - INSERM 0203 / CHU de Rennes / Université de Rennes
name: Bruno Laviolle, MD, PhD
role: STUDY_CHAIR
References: