Traditional (Traditional Chemoembolization) TACE Versus Microsphere TACE

NCT00936689 | Completed Phase 4

• 2 other identifiers: RAD01EudraCT 2006-003034-15
• Study Type: interventional
• Target: 178
• Locations: 1 country
• Sites: 5

Brief Summary

Background Hepatic intra-arterial chemoembolization (TACE) is proposed when potentially curative therapy (eg. surgical resection, percutaneous ablation)is no longer possible. Prospective and non-randomized retrospective studies showed TACE to be capable to increase survival vs controls. In 2002 the first results of two RCTs were published which had been conducted on unresectable HCC patients, designed to assess the impact produced by TACE on survival, demonstrated a statistically significant advantage in TACE treated patients compared to controls. The same results have been confirmed by a meta-analysis conducted on 14 trials published in literature. The limitations of TACE are represented however by the difficulties in obtaining a complete necrosis of the lesion treated and for this reason new embolization agents are being developed to increase the efficacy of TACE in HCC as the microsphere, in poly vinyl alcohol and co-acrylic acid that are not reabsorbable and induce permanent embolization. The first experimental studies using microsphere showed the good tolerability and the higher rate of tumor necrosis, but no RCTs have been conducted to investigate their impact on survival. Objectives. The primary aim of this study is to compare 2 years survival of patients randomized to selective traditional TACE or selective TACE via microspheres loaded with Doxorubicin. Secondary objectives investigate the time to progression of disease (radiologic and symptomatic) by radiologic, laboratory tests and the QoL questionnaire administration. Methods. This is a multicentre, randomized, open-label, active controlled study in HCC patients treated with standard TACE vs TACE with doxorubicin - loaded microsphere. The study comprises a selection period, a treatment period and a follow up phase with a total duration of 2 years from randomization. Expected results. The sample size(alfa 5%, power 80%) is adequate to detect a 20% difference between TACE with microsphere vs traditional TACE.

Conditions

Carcinoma, Hepatocellular

Keywords

Hepatocellular carcinoma;; Chemoembolization;; DC-Beads.

Outcome Measures

Primary Outcomes (1)

• survival of all randomized patients at month 24 (favorable event). Mortality by month 24 and withdrawal from the study will be considered to be unfavorable events.

  From first TACE treatment to month 24

Secondary Outcomes (1)

• Radiological tumor response; TTSP; TTP; Overall duration of response; Quality of life; ECOG score; Impact on liver function; No.of treatments administered.

  From first TACE to month 24

Study Arms (2)

Traditional TACE

SHAM COMPARATOR

Chemoembolization by standard technique: epirubicin (maximum dose of 75 mg) conjugated with an oil-based contrast medium (Lipiodol) at the maximum dose of 15 ml + gelatin sponge particles(particles of transient embolization material, required to obstruct the treated vessel).

Procedure: Selective traditional TACE

TACE with microsphere

ACTIVE COMPARATOR

Procedure: Selective TACE via microsphere loaded with Doxorubicin

Interventions

Selective TACE via microsphere loaded with Doxorubicin PROCEDURE

Chemoembolization with microspheres: doxorubicin (maximum dose of 75 mg x vials of microspheres) loaded with non-reabsorbable microspheres (sulfate hydrospheres) at the dose of 2 ml per vial (definitive embolization).

Also known as: DC-beads

TACE with microsphere

Selective traditional TACE PROCEDURE

Traditional chemoembolization: epirubicin (maximum dose of 75 mg) conjugated with Lipiodol at the maximum dose of 15 ml + Spongel.

Also known as: TACE

Traditional TACE

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of HCC: based on the Guidelines issued by AASLD (American Association for the Study of Liver Diseases) (latest diagnostic radiological imaging performed within 1 month from enrolment)
• HCC for which transplantation, surgical resection or percutaneous ablation are not indicated
• Absence of extrahepatic cancer involvement
• Absence of portal vein thrombosis, with the exception of thrombosis of a segment branch of the portal vein
• Child-Pugh class A or B
• Performance status: ECOG 0-2 (WHO)
• Target liver lesion measurable as per WHO modified EASL criteria
• Life expectancy of at least 3 months in absence of treatments.
• Prior surgical or locoregional ablation or TACE treatments are allowed for lesions other than the target lesion treated and monitored to define tumor response.
• The following laboratory parameters must be met:
• Creatinine ≤ 1.50 mg/dL, Bilirubin ≤ 2.5 mg/dL, Albumin \>= 30 g/L White blood cells \>= 1.5 x 109/L, PLT \>= 50 x 109/L, PT \>= 50%
• Signature of informed consent obtained.

You may not qualify if:

• Infiltrative HCC
• Liver tumor is undefined, unmeasurable or not assessable
• Occlusive thrombosis of the common portal trunk or of a main branch (right or left).
• Ascites, F3-type varices.
• Contraindications to arteriography
• Hepatofugal portal flow
• Presence of hemodynamically relevant abnormalities of hepatic arterial structure, such as not to allow for a correct and safe delivery of microspheres.
• Prior TACE to the target lesions
• Presence of chronic or acute co-morbidities (to lungs, heart, kidneys or brain) because of which the patient is not eligible to receive the treatment foreseen by the protocol.
• Prior neoplasias in the 5 preceding years or concomitance of other neoplasias at enrolment, wtih the exception of cutaneous basal cell or squamous cells carcinoma or carcinoma in situ of the uterine cervix
• Presence of localized or systemic infections (with the exception of HIV infecton responsive to therapy).
• Pregnant women (women of child-bearing potential will have a pregnancy test done) and breastfeeding women;
• Known or suspect hypersensitivity to the investigational drug or to the investigational pharmacological class;
• Patients presenting with severe clinical conditions which in the opinion of the investigator contraindicate patient participation in the study;
• Patients who are not capable of complying with the procedures established by the protocol and of signing the informed consent. In case of minors or incapacitated patients unable to release their informed consent to take part in the study, the consent must be released and signed also by the parents/guardian or by the legal representative. Minors or incapacitated patients must as well sign the informed consent to the best of their ability.

Sponsors & Collaborators

• Rita Golfieri: lead

Study Sites (5)

Ospedali Riuniti di Bergamo

Bergamo, BG, 24121, Italy

Location

Azienda Ospedaliero-Universitaria, Policlinico S.Orsola-Malpighi

Bologna, Bologna, 40138, Italy

Location

Azienda Ospedaliera Universitaria Pisana - Stabilimento di Cisanello

Pisa, PI, 56100, Italy

Location

Azienda Ospadaliera Universitaria S.Giovanni Battista - Molinette

Torino, TO, 10121, Italy

Location

Azienda Ospedaliera Universitaria S.Maria della Misericordia

Udine, UD, 33100, Italy

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Doxorubicin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Rita Golfieri, MD

  Azienda Ospedaliero-Universitaria, Policlinico S.Orsola-Malpighi

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: July 9, 2009
• First Posted: July 10, 2009
• Study Start: March 1, 2008
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2012
• Last Updated: December 24, 2012

Record last verified: 2012-12

Locations

IT (5)