Transarterial Chemoembolization Prior to Transplantation for Hepatocellular Carcinoma (CATCH)

Efficacy of Transarterial Chemoembolization With DC-BeadsR Prior to Liver Transplantation for Hepatocellular Carcinoma on Patient Survival : A Prosepctive Multicentre and Randomized Study

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.

Study Overview

• Status: Terminated
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Other: Intra-arterial administration of DC BeadsR

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.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Créteil, France, 94010
    • Hôpital Henri Mondor - Assistance Publique-Hôpitaux de Paris
  • Grenoble, France, 38000
    • Hôpital Michalon, CHU de Grenoble
  • Lille, France, 59000
    • Hôpital Claude Huriez, CHU de Lille
  • Lyon, France, 69000
    • Hôpital de la Croix Rousse, HCL, Lyon
  • Paris, France, 75000
    • Hôpital Saint-Antoine / APHP
  • Rennes, France, 35033
    • Hopital Pontchaillou
  • Tours, France, 37000
    • Hôpital Trousseau, CHU de Tours

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Usual care
Experimental: 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	Other: Intra-arterial administration of DC BeadsR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	Intention to treat survival at 3 years following inscription on the waiting list for liver transplantation in patient with hepatocellular carcinoma	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence rate		3 years
Dropout rate	Dropout rate (tumor progression beyond transplanted criteria and all causes mortality)	3 years
Post-transplantation survival rate		3 years
Allograft survival		3 years
Time to dropout		3 years
TACE-induced complications (local and general)		3 years
Contrast agent - induced complications		3 years
Doxorubicin-induced complications		3 years
Efficacy of TACE	Efficacy of TACE (morphological response to TACE: captation rate of Lipiodol and morphological response (RECIST guidelines), as well as histological criteria: percentage of necrosis on pathological examination)	3 years

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Investigators: Principal Investigator: Philippe COMPAGNON, MD, Service de Chirurgie Digestive - Transplantation Hépatique / Hôpital Henri Mondor - Assistance Publique-Hôpitaux de Paris / Faculté de Médecine - Université Paris-Est; Principal Investigator: Karim BOUDJEMA, MD PhD, Service de Chirurgie Hépato-biliaire et Digestive, Transplantation Hépatique / CHU de Rennes / Université de Rennes 1; Study Chair: Bruno Laviolle, MD, PhD, Service de Pharmacologie et CIC - INSERM 0203 / CHU de Rennes / Université de Rennes

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): May 28, 2014
• Study Completion (Actual): February 16, 2016

Study Registration Dates

• First Submitted: August 28, 2012
• First Submitted That Met QC Criteria: August 28, 2012
• First Posted (Estimate): August 30, 2012

Study Record Updates

• Last Update Posted (Actual): April 12, 2019
• Last Update Submitted That Met QC Criteria: April 10, 2019
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Liver transplantation; Hepatocellular carcinoma; Transarterial Chemoembolization
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: 2012~A00269-34