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

Phase 4
20 Years
Open (Enrolling by invite only)
Hepatocellular Carcinoma

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Trial Information

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

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

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

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

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

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.

Inclusion Criteria:

1. Patients with confirmed diagnosis of HCC as stated below

- Cirrhotic subjects: Clinical diagnosis by AASLD criteria

- Non-cirrhotic subjects: histological confirmation is mandatory

2. Patient with HCC not suitable for radical therapies such as resection, liver
transplantation or percutaneous therapies or patient is indicated for these therapies
but there is a contraindication for them or patient himself rejects above treatments
and wants to do TACE (Indication for hepatectomy, liver transplantation, local
ablation is decided by doctors of each center)

3. Multinodular or single nodular tumor over 5cm, (In the case of single nodule less
than 5cm, if curative treatment is contraindicated or the patient rejects curative

4. Hypervascular lesion showing contrast enhancement in the early stage at the contrast
media bolus injection CT or MRI.

5. At least one uni-dimensional lesion measurable according to the Modified RECIST
criteria by CT-scan or MRI

6. No invasion in the blood vessel (hepatic portal, hepatic vein) or bile duct by the CT
or MR

7. Eastern Cooperative Oncology Group performance status is 0 - 1

8. Child-Pugh classification is A or B7

9. Proper blood, liver, renal, heart function: testing result within 2 weeks from
registry of this study is followed:

- white blood cell number : > 3,000/mm2

- platelet number : > 5 x 104/mm3

- blood bilirubin : < 3.0 mg/dL

- ASL, ALT is within 5 times of normal range of each organ

- serum creatinine : < 1.5 mg/dL

- hemoglobin : > 8.0 g/dL

10. Over 20 years old

11. Expected survival more than 6 months

12. Patients who are willing to do regular visit, laboratory test, and radiological exam

13. Prior written patient consent

Exclusion Criteria:

1. ECOG performance status 2 or more, Child-Pugh class B8 or more

2. Diffuse HCC or presence of vascular or biliary invasion or extrahepatic spread.

3. Vascular or biliary invasion

4. Extrahepatic metastasis (Any lymph nodes measuring ≥ 10mm along the short axis)

5. Tumor burden involving more than 50% of the liver

6. Patients previously treated with any anti-cancer therapy for HCC except hepatic
resection or early recurrence within 1 year after resection

7. Liver cancer rupture

8. History of biliary tract repair or endoscopic biliary tract treatment

9. Clinically important refractory ascites or pleural fluid

10. Any contraindications for hepatic embolization procedures

- Known hepatofugal blood flow

- Arterio-venous shunt

- Impaired clotting test (platelet count < 5 x 104/mm3, PT-INR > 2.0)

11. Any contraindication for doxorubicin administration

12. Contrast media allergy contraindicating angiography

13. Acute or active following diseases

- Heart failure can't control, angina pectoris and/or arrhythmia diseases

- Myocardial infarction within the last 6months,

- Renal failure

- Active infection (virus infection can be accepted)

- Active hemorrhage of digestive system

- Other malignant tumor history

- Hepatic coma or acute mental disease

14. Pregnant, nursing or childbearing age women and men who are actively sexually
available and don't want to or can't do contraception

15. Safety concerns based on researcher's judge

Type of Study:


Study Design:

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

Outcome Measure:

tumor response

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Jin Wook Chung, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Seoul National University Hospital


Korea: Food and Drug Administration

Study ID:




Start Date:

April 2011

Completion Date:

December 2015

Related Keywords:

  • Hepatocellular Carcinoma
  • hepatocellular carcinoma
  • chemoembolization
  • drug eluting beads
  • HCC
  • Liver cancer
  • Korea
  • Carcinoma
  • Carcinoma, Hepatocellular