A Single Center Experience:Safety and Efficacy of DEB-TACE Performed With a Novel Reflux-control Microcatheter in Patients With Early and Intermediate HCC.
Conditions: Hepatocellular Carcinoma, Liver Cancer
Sponsor: Juan José Ciampi Dopazo

 
OFFICIAL TITLE OF THE STUDY: 
 
 
 
A SINGLE CENTER EXPERIENCE: SAFETY AND EFFICACY OF DEB-TACE PERFORMED 
WITH A NOVEL REFLUX-CONTROL MICROCATHETER IN PATIENTS WITH EARLY AND 
INTERMEDIATE HCC. 
 
 
 
 
NCT Number : Not available  
 
 
 
Date of the document : October/ 20/  2020. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

BACKGROUND: 
 
Hepatocellular carcinoma is the fifth most frequent cancer in the world, with a 
diagnosis of more than 500,000 new cases per year. It is considered the third leading 
cause of cancer mortality and presents well-defined risk factors. Liver cirrhosis is the 
main risk factor for developing HCC, therefore screening programs in cirrhotic patients 
will allow the early diagnosis of this neoplasia. Despite this, most HCCs are diagnosed 
at a stage in which the application of curative therapies is no longer possible.  
 
Hepatic transarterial chemoembolization (TACE) belongs to the arterially directed 
embolization therapies for the treatment of unresectable early-to-advanced 
hepatocellular carcinoma (HCC). It is the only therapy that has shown to improve 
survival in intermediate-stage HCC. 
Drug-eluting beads (DEB)-TACE has shown to provide slow drug elution, reduced liver 
and systemic toxicity, increased local drug concentration, and tissue necrosis. 
Aside from TACE, other transarterial options include bland embolization, or hepatic 
artery embolization (HAE), and transarterial radioembolization (TARE). All have an 
acceptable safety profile, and each has its associated procedural and peri-procedural 
complications. One potential complication that may occur during all embolization 
procedures is when the embolic material migrates outside of the desired treatment 
area, leading to non-target embolization (NTE). In fact, when collateral vessels are 
embolized, there is a risk that these may be feeders of non-target tissue or organs. 
NTE following TACE in particular may lead to a double-layer problem: dangerous 
components affecting healthy tissue, one ischemic and one related to cytotoxicity from 
the chemotherapeutic agent, which may have clinical consequences, and potential 
incomplete treatment of the lesion (due to beads being "deviated" from target).  
 
 NTE is highly recognized, but often thought to be uncommon, and although different 
complications can be caused by it, there may appear to be no evidence of NTE during 
the intraprocedural imaging.  
To avoid the complications due to NTE, apart from the importance of the pre, intra and 
post-procedural imaging, and the thorough study of the anatomical picture, the 
catheters/microcatheters should also be chosen with reason and care. In particular, 
selective catheterization should be achieved by placing the microcatheter tip as close 
as possible to the target, through the specific branch/branches supplying it.  
However, even with the microcatheter selectively positioned in the vessel to be 
embolized, the risk of NTE might not be eliminated, since it could happen as a result of 
changes in flow dynamics that occur during embolization, particularly when the 
endpoint is stasis. These changes could result in reflux into non-target territories and, 
as such, might be better prevented with the use of microcatheters intended to reduce 
reflux. To this purpose, the use of a dedicated delivery device should be taken into 
consideration, in order to optimize and save time during the procedure.  
 
Microcatheters are commonly used during most arterial embolization procedures, and 
as explained above, there is a strong rationale to use a reflux-control microcatheter – 
like SEQURE® (Guerbet, Roissy-France) – for DEB-TACE.  

The main expectation is to achieve technical success with SEQURE ® in all patients with 
a reachable target lesion, with the intent not only to minimize potential damage to 
surrounding tissue, but also to potentially deliver more treatment embolics, as all the 
beads are (re)directed towards the target.  
The use of small diameter particles (100 micron-TANDEM ® spheres- Varian Medical 
Devices, Palo Alto, CA, US), induces superior tumor necrosis response (Urbano et al., 
European Journal of Radiology, 2020); with the synergistic effect of being administered 
through the SEQURE anti-reflux protection system, there is reason to believe that it 
will be possible to administer maximum doses of doxorubicin, while avoiding the 
occlusion of non-target arterial segments (SYNERGIC EFFECT). 
 
STUDY PROPOSAL: 
 
Investigators  propose a prospective observational study with data collection from a 
single center (Virgen de las Nieves University Hospital-Granada), for a period that 
ranges October 2020-December 2021. Here summarized the inclusion criteria and 
contraindications: 
 
Inclusion criteria 
 
- 
BCLC B and or some case BCLC A 
- 
Both genders 
- 
Over 18 years. 
- 
Bilirubin less than 3 gr/dl. 
- 
No contraindications to the use of iodinated contrast 
- 
Absence of chronic kidney disease  
- 
ECOG 0-1. 
- 
Absence of encephalopathy. 
- 
Informed consent. 
 
Contraindications 
 
• Advanced liver disease. 
• Thrombosis or reversal of portal flow. 
• Vascular invasion. 
• Extrahepatic spread. 
• Contraindication to administration of cytostatics. 
• Contraindication to angiographic procedure. 
 
 
HYPOTHESIS: 
The use of 100 micron-TANDEM ® spheres  will be studied  with the synergistic effect 
of being administered through SEQURE® microcatheter anti-reflux protection system, 
which may allow the administration of the maximum doses of doxorubicin, avoiding 
the undesired occlussion of collateral arterial segments (SYNERGIC EFFECT). Other 
variables to study are: access route, procedural time and fluoroscopy time. 
 

The information will be collected through the electronic database of the patient 
(includes laboratory data). Patients will be evaluated starting from the date of 
inclusion as candidates for TACE treatment, and followed up for 6 months (unless 
patients are lost to clinical follow-up or death occurs). Mortality data are obtainable by 
searching the electronic history of the patient.  
Changes in the serum levels of  aspartate aminotransferase (AST), alanine 
aminotransferase (ALT), Alkaline phosphatase (ALP), bilirubin, albumin and patients‘ 
complete hematological profile, as well as serum lipase and amylase levels within the 
1st week post-TACE to detect pancreatitis, will be evaluated at the following time-
points: pre-embolization, at one month, three months, and six months. Computed 
tomography (CT) or Magnetic Resonance Imaging (MRI) with contrast will be 
performed at the same time-points as just indicated; modified Response Evaluation 
Criteria in Solid Tumors ( m-RECIST)  will be used, and images will be assessed by two 
experienced radiologists (any discordant interpretation will be solved through team 
consensus). All serologic toxicities would be classified according to common 
terminology criteria for adverse effects. On this scale, severe hepato-toxicity (grade 3) 
is classified as the increase of up to 5 times the normal limit of AST, ALT, FA or the 
increase of bilirubin level to over 3 g/dl. 
 
 
PATIENT SELECTION: 
 
 Between October 2020 and December 2021, and expected number of 30 patients will 
be treated. The diagnosis of Hepatocellular carcinoma (HCC) will confirm in accordance 
with the American Association for the Study of Liver Diseases guidelines and HCC  
staged according to Barcelona Clinic Liver Cancer (BCLC) system. 
 
DEB-TACE is indicated according to clinical practice guidelines referred above. 
 
 
TECHNICAL PROCEDURE: 
 
  The embolization will be performed using TANDEM ®  spheres (each cc of spheres can 
be loaded with up to 50 mg of doxorubicin. The maximum dose of doxorubicin used 
per procedure was 150 mg, corresponding to 3 cc of spheres) and SEQURE ® 
microcatheter in a super-selective tumour´s arterial position avoiding undesired 
arterial branches. The procedure will consider super-selective when the micro-catheter 
tip reached the tumour feeding artery. Each cc of microspheres will mix with 7-10 cc of 
non-ionic contrast medium. Embolization endpoint is considered vascular stasis or 150 
mg of Doxorubin administered. 
 
OBJECTIVES AND END-POINTS: 
 
Efficacy:  
• Technical success will be defined as a composite outcome measurement: ability 
to place the microcatheter inside the required vascular segment and qualitative 
assessment of microspheres deposition in the target tumour. 

 
• Time to Progression (TTP) [Time Frame: 6 months]. Time at which progression 
is first observed in a tumor assessment according to mRECIST as assessed by  
CT or MRI. 
 
• Objective Response Rate (ORR) and Disease Control Rate (DCR) [Time Frame: 
Assessed at 1, 3, and 6 months after first treatment]. ORR is defined as a 
complete or partial response among the total number of cases  and DCR is 
defined as a complete, partial response or stable disease among the total 
number of cases , according to mRECIST evaluated by CT or MRI. Time to 
retreatment included as consequential secondary objective. 
 
 
Safety:  
 
• Adverse Events (AEs) and Serious Adverse Events (SAE) [Time Frame: Assessed 
at 1, 3, and 6 months after first treatment. The incidence of emerging AE and 
SAE will be summarized according to standardized qualification criteria [Journal 
of Vascular Interventional Radiology (JVIR) SAE], including pancreatitis, 
cholecystitis, clinical presentations, postembolization syndrome (PES), etc. 
 
• Non Target embolization (NTE) by thorough angiographic assessment of the 
whole liver vasculature after TACE, as well as Cone Beam Computed 
Tomography (CBCT) performed immediately following embolization (within 
30 minutes from the end of procedure) to evaluate off-target distribution. 
 
• Health-Related Quality of Life questionary (HRQOL): pre-treatment and post-
treatment quality of life assessment using the specific questionnaire for 
functional assessment for cancer treatment (FACT-G). 
 
 
Study flowchart 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TANDEM ® / SEQURE ® GROUP PATIENTS 
ACCORDING TO Barcelona Clinic Liver Cancer (BCLC)-EARLY TO 
INTERMEDIATE STAGE CRITERIA 
STUDY HYPOTHESIS:  
1-LIMITED REFLUX DURING EMBOLIZATION – DAMAGE LESS (SAFETY) 
2-GREATER TUMOR NECROSIS IN TARGET LESIONS, SO BETTER RESPONSE 
(EFFICACY) 
PRIMARY OBJECTIVES: 
1- Technical success 
2- ORR by m-RECIST criteria 
3-lack of NTE (also through CBCT imaging) 
4- rate of Major complications and AEs (including pancreatitis and 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DEB-TACE PROCEDURES: 
 
The embolization will be performed according to routine clinical practice, with drug-
eluting microspheres (100-micron TANDEM ® spheres), pre-loaded with 50 mg 
doxorubicin per ml (1 syringes of 3 ml). Injection will be according to manufaturer 
recommendations, with a selective or superselective approach depending on lesion 
and feeder localization. 
 
 
 
SECONDARY OBJECTIVES: 
1-TTP 
2-HRQOL 
3-Time to retreatment