Safety and Efficacy of DEB-TACE Performed With a Novel Reflux-control Microcatheter in Patients With HCC

NCT04653701 | Unknown DMC FDA Drug FDA Device

• 1 other identifier: 5077
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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 - 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), 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: We 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.

Conditions

Hepatocellular Carcinoma; Liver Cancer

Keywords

embolization; chemoembolization; superselective embolization

Outcome Measures

Primary Outcomes (6)

• Objective Response Rate (ORR)

  ORR is defined as a complete or partial response among total of treated cases, according to mRECIST evaluated by CT or MRI. The value of these data is a percentage considering tumour diameter before and after treatment.

  Assessed at 3 months after patient inclusion

• Objective Response Rate (ORR)

  ORR is defined as a complete or partial response among total of treated cases, according to mRECIST evaluated by CT or MRI. The value of these data is a percentage considering tumour diameter before and after treatment.

  Assessed at 6 months after patient inclusion

• Disease Control Rate (DCR)

  DCR is defined as a complete, partial response or stable disease among total of treated cases, according to mRECIST evaluated by CT or MRI. The value of these data is a percentage considering tumour diameter before and after treatment.

  Assessed at 3 months after patient inclusion

• Disease Control Rate (DCR)

  DCR is defined as a complete, partial response or stable disease among total of treated cases, according to mRECIST evaluated by CT or MRI. The value of these data is a percentage considering tumour diameter before and after treatment.

  Assessed at 6 months after patient inclusion

• Adverse Events (AEs) and Serious Adverse Events (SAE)

  The incidence of emerging AE and SAE will be summarized according to standardized qualification criteria (JVIR SAE), including pancreatitis, cholecystitis, clinical presentations, PES, etc.

  Assessed up to 30 days after patient inclusion

• Technical success

  Defined as a composite outcome measurement: ability to place the micro-catheter inside the required vascular segment and qualitative assessment of microspheres deposition in the target tumour.

  up to 1 hour after patient inclusion (or after patient treatment)

Study Arms (1)

Patients with hepatocellular carcinoma treated with TAMDEM® 100 micron and SEQURE® microcatheter

Patients included in this study and with chemoembolization indications will be superselective embolized using TAMDEM® 100 micron preloaded particles (Doxorubicin) and SEQURE® microcatheter combination (SYNERGIC EFFECT). Objective tumoral response and 30 days-complications (Safety) are primary outcomes.

Combination Product: Chemoembolization with preloaded microparticles 100 micron and reflux control microcatheter

Interventions

Chemoembolization with preloaded microparticles 100 micron and reflux control microcatheter COMBINATION_PRODUCT

We will perform chemoembolization technique in those patients (during 1 year) with indications for this treatment in relation with guidelines (early and intermediate hepatocellular carcinoma). Specific microcatheter and microparticles will be use (Mentioned above)

Patients with hepatocellular carcinoma treated with TAMDEM® 100 micron and SEQURE® microcatheter

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients will be evaluated starting from the date of inclusion as candidates for TACE treatment, and followed up for 6 months . Mortality data are obtainable by searching the electronic history of the patient. Changes in the serum levels of AST, ALT, FA, 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. CT or MRI with contrast will be performed at the same time-points as just indicated; m-RECIST criteria will be used. All serologic toxicities would be classified according to common terminology criteria for adverse effects.

You may qualify if:

• 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.

You may not qualify if:

• Advanced liver disease.
• Thrombosis or reversal of portal flow.
• Vascular invasion.
• Extrahepatic spread.
• Contraindication to administration of cytostatics.
• Contraindication to angiographic procedure.

Sponsors & Collaborators

• Juan José Ciampi Dopazo: lead

Study Sites (1)

Juan Jose Ciampi Dopazo

Granada, 18014, Spain

RECRUITING

Related Publications (5)

• Delicque J, Guiu B, Boulin M, Schwanz H, Piron L, Cassinotto C. Liver chemoembolization of hepatocellular carcinoma using TANDEM(R) microspheres. Future Oncol. 2018 Nov;14(26):2761-2772. doi: 10.2217/fon-2018-0237. Epub 2018 Jun 28.

  PMID: 29953255 BACKGROUND

• Lammer J, Malagari K, Vogl T, Pilleul F, Denys A, Watkinson A, Pitton M, Sergent G, Pfammatter T, Terraz S, Benhamou Y, Avajon Y, Gruenberger T, Pomoni M, Langenberger H, Schuchmann M, Dumortier J, Mueller C, Chevallier P, Lencioni R; PRECISION V Investigators. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol. 2010 Feb;33(1):41-52. doi: 10.1007/s00270-009-9711-7. Epub 2009 Nov 12.

  PMID: 19908093 RESULT

• Urbano J, Echevarria-Uraga JJ, Ciampi-Dopazo JJ, Sanchez-Corral JA, Cobos Alonso J, Anton-Ladislao A, Pena-Baranda B, Nacarino-Mejias V, Gonzalez-Costero R, Munoz Ruiz-Canela JJ, Perez-Cuesta J, Lanciego C, de Gregorio MA. Multicentre prospective study of drug-eluting bead chemoembolisation safety using tightly calibrated small microspheres in non-resectable hepatocellular carcinoma. Eur J Radiol. 2020 May;126:108966. doi: 10.1016/j.ejrad.2020.108966. Epub 2020 Mar 19.

  PMID: 32278280 RESULT

• Aliberti C, Carandina R, Lonardi S, Dadduzio V, Vitale A, Gringeri E, Zanus G, Cillo U. Transarterial Chemoembolization with Small Drug-Eluting Beads in Patients with Hepatocellular Carcinoma: Experience from a Cohort of 421 Patients at an Italian Center. J Vasc Interv Radiol. 2017 Nov;28(11):1495-1502. doi: 10.1016/j.jvir.2017.07.020. Epub 2017 Sep 18.

  PMID: 28927662 RESULT

• Lopez-Benitez R, Richter GM, Kauczor HU, Stampfl S, Kladeck J, Radeleff BA, Neukamm M, Hallscheidt PJ. Analysis of nontarget embolization mechanisms during embolization and chemoembolization procedures. Cardiovasc Intervent Radiol. 2009 Jul;32(4):615-22. doi: 10.1007/s00270-009-9568-9. Epub 2009 Apr 23.

  PMID: 19387732 RESULT

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• JUAN JOSE CIAMPI DOPAZO, Dr

  University Hospital Virgen de las Nieves

  PRINCIPAL INVESTIGATOR

Central Study Contacts

JUAN JOSE CIAMPI DOPAZO, Dr

CONTACT

0034 669267932; jjciampidopazo@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator and Clinical Professor

Study Record Dates

• First Submitted: November 15, 2020
• First Posted: December 4, 2020
• Study Start: November 14, 2020
• Primary Completion: November 20, 2021
• Study Completion: February 20, 2022
• Last Updated: December 4, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Between September 2021 to March 2022

Locations

ES (1)