Drug-eluting Bead in Hepatocellular Carcinoma — REDEBUT  

Hepatocellular Carcinoma Clinical Trial

Official title: Multicenter Registry of Chemoembolization Using Drug-eluting Bead in Patients With Unresectable Hepatocellular Carcinoma

Status Completed

Clinical Trial Summary

In unresectable hepatocellular carcinoma, TACE using Lipiodol/anti cancer agent emulsion is the standard treatment and reported as a significantly better treatment through randomized comparison study like Llovet, etc. than conservative treatment. Recently, doctors do transarterial chemoembolization with drug-eluting bead, and it is proved less side effect and better efficacy than conventional TACE using Lipiodol in Precision V study by Dr. Lammer, etc. But, it could not defined improved survival rate as expected. This study's purpose is evaluating treatment efficacy, survival rate and safety of TACE using drug eluting bead by comparing to conventional TACE using doxorubicin/Lipiodol emulsion for unresectable hepatocellular carcinoma.

Clinical Trial Description

Comparison Between Drug-Eluting Bead vs conventional TACE.

Drug-eluting bead group : TACE using DC bead loading Doxorubicin. Conventional TACE group :

TACE using Doxorubicin/Lipiodol emulsion and gelatin sponge/PVA particle.

cTACE group was chosen by concurrent matched patients (age, sex, tumor stage, and Child-Pugh class are matched)

5.7 Technically considerable aspects of DC bead TACE group

1. Planned dose of doxorubicin. Each vial of DC Bead (2 ml of beads) should be loaded with 70-75 mg doxorubicin (loading dose, 35-37.5 mg doxorubicin / ml of beads).

• Early-stage HCC. As a general rule, each single treatment should include a planned dose of up to 75 mg doxorubicin loaded into one vial of DC Bead.

• Medium-sized (less than 8cm) / multinodular HCC. As a general rule, each single treatment should include a planned dose of up to 150 mg doxorubicin loaded into two vials of DC Bead.

• In large tumors (more than 8cm), even if unilobar, the separate treatment including two sessions 2-4 weeks apart is recommended.

• In bilobar tumors, both hepatic lobes should be treated in separate treatment sessions 2-4 weeks apart, in the absence of complications requiring a longer time interval between the two sessions. Obtaining confirmation that the liver enzymes did return to baseline before performing the second treatment session is recommended.

2. Choice of DC Bead size. Use of 100-300μm beads is recommended for a standard procedure. However, individual patient and tumor characteristics, particularly the identification of arterio-venous shunting, should be taken into account when the safety of the treatment and the choice of DC Bead size are determined.

• In the case of significant arterio-portal or hepatic venous shunting, embolization of the shunt with gelfoam pledgets is recommended before proceeding with DEBDOX. Confirmation that the shunt is no longer present must be obtained before DEBDOX can safely be performed. But, this study excludes the patients with arterio-portal or hepatic venous shunts.

• In large tumors, hepatic arterial flow does not reach 'near stasis' after injection of 2 vial of 100-300 μm DC beads. The recommendation is following: 2 vials of the 100-300 μm DC beads is best and then repeat 2 weeks later if the patient is doing well clinically.

3. DC Bead dilution. Mix loaded DC Bead with a non-ionic contrast medium. At least 5-10 ml of non-ionic contrast should be used per 1 ml of DC Bead (i.e., 10-20 ml are required to dilute one vial of DC Bead) prior to injection.

4. Catheter positioning. A superselective (i.e., segmental or subsegmental) approach should be used whenever possible by using a microcatheter. Use of 3D / MPR obtained from C-arm rotational angiography with a flat-panel detector system (cone-beam CT) is recommended, if available, to improve the accuracy in identifying tumor-feeding arteries. Such imaging allows for accurate targeting of the tumor. In addition, repeat cone beam CT should be performed after successful delivery of the DC Bead to confirm adequate targeting and saturation of the tumor(s).

• Segmental / subsegmental approach. Place the microcatheter into the segmental / subsegmental vessel feeding the tumor as distally as possible - but avoiding wedging the catheter to avoid reflux along the catheter shaft. Flow within the artery must be preserved.

• Lobar approach. Place the catheter as selectively as possible in the right or left hepatic artery. Pay attention to identifying the origin of the cystic artery as well as other arteries supplying flow to extra-hepatic organs such as the right gastric artery, para-esophageal or omental vessels among others. If identified, these vessels must be either embolized using coils or avoided by placing the catheter tip well beyond the origin of these vessels. In addition, forward flow into the desired vessel must be maintained as inadvertent administration of even a few DC Beads into these extra-hepatic vessels could have dire consequences.

5. Injection. The injection must be very slow. An injection rate of 1 ml of the contrast agent - DC Bead suspension per minute is recommended. Thus, it takes 10-20 minutes to infusion 1 vial of DC bead. Care should be taken to avoid sedimentation of the beads in the syringe by rotating the syringes or using a 3-way stopcock to gently suspend the beads in the solution.

6. Embolisation endpoint. Injection should be continued until "near stasis" is observed in the artery directly feeding the tumor (i.e., the contrast the contrast column should clear within 2-5 heart beats). At that point, injection should be stopped - regardless of the amount of beads that have been actually administered - to avoid reflux of embolic material. Once the embolisation endpoint has been achieved, no additional embolic material should be injected. If the "near stasis" endpoint is not obtained after injection of the scheduled volume of beads, no additional embolization should be performed. This patient is likely to benefit from a second course after imaging follow-up.

7. extrahepatic collateral vessels. In principle, DC bead is used for collateral arterial circulation (inferior phrenic artery, internal mammary artery, intercostal artery), but doctors can do bland embolization (PVC particle, gelatin sponge) based on their judgement.

8. Repeated treatment. In principle, treatment with the same method is repeated for every 2 - 3 months as tumor progression is observed. But, even if tumor progression is not observed, the treatment can be repeated for tumor repression. If there is no tumor left, contrast enhancement CT or MRI can be performed for every 2- 3 months as follow up.

5.8. Dose in study Dose of DC bead, anti cancer agent for TACE dose is decided by tumor size. So, this study just set up the maximum dose.

Drug-eluting bead group DC bead : 2 bottles DC bead absorbs 70-75mg per bottle. Doxorubicin loading to DC bead needs to be done 1.5 hours before using. The size of DC bead is 100-300 micrometer, and it can be used up to 2 bottles. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

• NCT number: NCT01332669
• Study type: Interventional
• Source: Seoul National University Hospital
• Status: Completed
• Phase: Phase 4
• Start date: April 2011
• Completion date: May 2015