Transarterial Chemoembolization Prior to Transplantation for Hepatocellular Carcinoma

NCT ID: NCT01676194

Last Updated: 2019-04-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2016-02-16

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.

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intra-arterial administration of DC BeadsR

Intra-arterial administration of DC BeadsR, (1 vial of 100-300 µm) as selectively as possible loaded with doxorubicin (50 mg per procedure) and mixed with an equal volume of contrast medium. The first injection will be performed within 21 days following enlisting and repeated 1-2 times 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

Group Type: EXPERIMENTAL

Intra-arterial administration of DC BeadsR

Intervention Type: OTHER

Control

Usual care

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Intra-arterial administration of DC BeadsR

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rennes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philippe COMPAGNON, MD

Role: PRINCIPAL_INVESTIGATOR

Service de Chirurgie Digestive - Transplantation Hépatique / Hôpital Henri Mondor - Assistance Publique-Hôpitaux de Paris / Faculté de Médecine - Université Paris-Est

Karim BOUDJEMA, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Service de Chirurgie Hépato-biliaire et Digestive, Transplantation Hépatique / CHU de Rennes / Université de Rennes 1

Bruno Laviolle, MD, PhD

Role: STUDY_CHAIR

Service de Pharmacologie et CIC - INSERM 0203 / CHU de Rennes / Université de Rennes

Locations

Hôpital Henri Mondor - Assistance Publique-Hôpitaux de Paris

Créteil, , France

Hôpital Michalon, CHU de Grenoble

Grenoble, , France

Hôpital Claude Huriez, CHU de Lille

Lille, , France

Hôpital de la Croix Rousse, HCL, Lyon

Lyon, , France

Hôpital Saint-Antoine / APHP

Paris, , France

Hôpital Pontchaillou

Rennes, , France

Hôpital Trousseau, CHU de Tours

Tours, , France

Countries

France

Other Identifiers

2012~A00269-34

Identifier Type: -

Identifier Source: org_study_id