Clinical trial NCT03734068: Chemoembolization Using LifePearl Polyethylene Glycol Drug Eluting Microspheres With Doxorubicin in HCC
Official title: Observational Prospective Study on Chemoembolization Using LifePearl Polyethylene Glycol Drug Eluting Microspheres With Doxorubicin in Patients With Primary Un-resectable Liver Cancer (Hepatocellular Carcinoma)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular carcinoma
Transarterial chemoembolization
Tumor response
Lifepearls
Lead sponsor: International Group of Endovascular Oncology
Sponsor class: OTHER
First posted: 2018-11-07
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: un-resectable hepatocellular carcinoma that are indicated for TACE treatment

Brief summary: The aim of this study is to collect data on efficacy and tolerability on a large series of patient of different Italian hospitals in order to support the validation of LifePearl with robust and consistent clinical evidence. Since TACE in treating HCC is considered a more common and accepted approach, this study will be focused on evaluating treatment efficacy and safety of LIFDOX for un-resectable hepatocellular carcinoma.

Detailed description: Hepatocellular carcinoma (HCC) is the fifth most common type of cancer in men and the seventh in women and is the third most common cause of death from cancer worldwide. The overall incidence of HCC remains high in developing countries and is steadily increasing in most industrialized countries.

Trans-arterial chemoembolization (TACE) is the most used treatment for patients with un-resectable hepatocellular carcinoma (HCC), because it improves median survival and tumor response. The application of drug-eluting bead to this procedure has significantly increased TACE efficacy, while reducing systemic drug leakage, liver toxicity and adverse events. These beads deliver the toxic drugs directly to the arterial capillary bed of the tumor, and release them in a controlled manner. This method lower the systemic exposure to chemotherapeutics, while increasing their local concentration, resulting in a greater tissue necrosis than classic trans-arterial chemoembolization.

TACE is indicated for patients with multinodular liver cancer that have no vascular invasion and extrahepatic diffusion. TACE is also strongly suggested for patients with un-resectable liver primary tumor (HCC and cholangiocarcinoma) and chemo-resistant liver metastases, mainly from colorectal cancer carcinoma (CRC), and is widely performed in 32% of patients with un-resectable HCC at initial diagnosis and in 58% of those with recurrent HCC. It appears, moreover, to be particularly useful if carried out with new embolization materials, such as doxorubicin.

Trans-arterial chemoembolization is constantly improving; from the original conventional TACE using Lipiodol and sponge particles, some years ago it evolved into precision TACE, thanks to the availability of drug-eluting microspheres. Microspheres retain the ability to bind positively charged chemotherapeutic drugs (i.e.: doxorubicin) and release them in a prolonged and sustained kinetic at tumor site while determining a permanent embolization of the feeding arteries. Consequently, less systemic exposure of drug is observed, with a benefit for the patients in term of toxicity, quality of life and hospitalization.

Recently, new drug-eluting beads in polyethylene glycol has been made available, termed LifePearl Polyethylene glycol drug eluting microspheres (Terumo, Microvention, Tustin, CA, USA), which are offered as a syringe presentation, for an easier loading process. More interestingly, LifePearl are precisely calibrated, in a range ≤ 50 micron, potentially leading to a more distal and targeted distribution into the tissues; in addition, they are endowed with a prolonged time in suspension after dilution in contrast medium, which makes the administration more smooth, predictable and reproducible. Because of the above improvements, LifePearl are now widely used in several hospital for the Transarterial chemoembolization as everyday clinical practice, for the hepatic intra-arterial infusion of doxorubicin or irinotecan respectively for the therapy of primary and metastatic liver cancer.

The aim of this study is to collect data on efficacy and tolerability on a large series of patient of different Italian hospitals in order to support the validation of LifePearl with robust and consistent clinical evidence. Since TACE in treating HCC is considered a more common and accepted approach, this study will be focused on evaluating treatment efficacy and safety of LIFDOX for un-resectable hepatocellular carcinoma.

Eligibility criteria: Inclusion Criteria:

* Patients with confirmed diagnosis of HCC with CT scan, MRI or biopsy
* Patient with un-resectable HCC and not indicated for other radical therapies, or waiting for transplant
* Multinodular or single nodular tumor extended to \<50% of the liver
* Hyper vascular lesion showing contrast enhancement in the early stage at the contrast media bolus injection CT or MRI.
* At least one uni-dimensional lesion measurable according to the Modified RECIST criteria by CT-scan or MRI
* No invasion in the blood vessel (hepatic portal, hepatic vein) or bile duct by the CT or MR
* Eastern Cooperative Oncology Group performance status is 0 - 1
* Proper blood, liver, renal, heart function
* Over 18 years old
* Expected survival more than 6 months
* Prior written patient consent

Exclusion Criteria:

* Extrahepatic metastasis (Any lymph nodes measuring ≥ 10mm along the short axis)
* Tumor burden involving more than 50% of the liver
* History of biliary tract repair or endoscopic biliary tract treatment
* Clinically important refractory ascites or pleural fluid
* Any contraindications for hepatic embolization procedures
* Any contraindication for doxorubicin administration
* Contrast media allergy contraindicating angiography
* Acute or active cardiac, hepatic or renal diseases
* Pregnant, nursing or childbearing age women and men who are sexually active and don't want to or can't do contraception

Primary outcomes:
measure: Tumor response
timeFrame: 6 months
Secondary outcomes:
measure: Number of adverse events
timeFrame: 1 year
measure: time to progression
timeFrame: 1 months
measure: number of treatment required to achieve objective response in HCC patients
timeFrame: 1 year
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Antonio Nicolini
Study officials:
affiliation: UOSD Radiologia Interventistica, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza, 28, 20122 Milano, Italia
name: Antonio Nicolini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Oncology-Hematology, Azienda Ospedaliera Ospedali Riuniti Marche Nord, P.O. San Salvatore, via C. Lombroso 1, 62122 Pesaro, Italy
name: Giammaria Fiorentini, MD
role: STUDY_CHAIR
References: