Traditional (Traditional Chemoembolization) TACE Versus Microsphere TACE (PRECISION-IT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Rita Golfieri, University of Bologna
ClinicalTrials.gov Identifier:
NCT00936689
First received: July 9, 2009
Last updated: December 21, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Carcinoma, Hepatocellular
Procedure: Selective TACE via microsphere loaded with Doxorubicin
Procedure: Selective traditional TACE
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Hepatocellular Carcinoma (HCC)by Selective Traditional Chemoembolization(TACE)Versus Selective TACE Via Microspheres Loaded With Doxorubicin: a Multicentre,Randomized,Open Label,Controlled Study.

Resource links provided by NLM:


Further study details as provided by University of Bologna:

Primary Outcome Measures:
  • 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. [ Time Frame: From first TACE treatment to month 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Radiological tumor response; TTSP; TTP; Overall duration of response; Quality of life; ECOG score; Impact on liver function; No.of treatments administered. [ Time Frame: From first TACE to month 24 ] [ Designated as safety issue: Yes ]

Enrollment: 178
Study Start Date: March 2008
Study Completion Date: December 2012
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Sham Comparator: Traditional TACE
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
Traditional chemoembolization: epirubicin (maximum dose of 75 mg) conjugated with Lipiodol at the maximum dose of 15 ml + Spongel.
Other Name: TACE
Active Comparator: TACE with microsphere Procedure: Selective TACE via microsphere loaded with Doxorubicin
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).
Other Name: DC-beads

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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;
  • Use of investigational drugs in the last month prior to inclusion into 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.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00936689

Locations
Italy
Ospedali Riuniti di Bergamo
Bergamo, BG, Italy, 24121
Azienda Ospedaliera Universitaria Pisana - Stabilimento di Cisanello
Pisa, PI, Italy, 56100
Azienda Ospadaliera Universitaria S.Giovanni Battista - Molinette
Torino, TO, Italy, 10121
Azienda Ospedaliera Universitaria S.Maria della Misericordia
Udine, UD, Italy, 33100
Azienda Ospedaliero-Universitaria, Policlinico S.Orsola-Malpighi
Bologna, Italy, 40138
Sponsors and Collaborators
Rita Golfieri
Investigators
Principal Investigator: Rita Golfieri, MD Azienda Ospedaliero-Universitaria, Policlinico S.Orsola-Malpighi
  More Information

No publications provided

Responsible Party: Rita Golfieri, MD, University of Bologna
ClinicalTrials.gov Identifier: NCT00936689     History of Changes
Other Study ID Numbers: RAD01, EudraCT 2006-003034-15
Study First Received: July 9, 2009
Last Updated: December 21, 2012
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by University of Bologna:
Hepatocellular carcinoma;
Chemoembolization;
DC-Beads.

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014