Clinical trial NCT00261378: Prospective Randomised Study of Doxorubicin in the Treatment of Hepatocellular Carcinoma by Drug-Eluting Bead Embolisation
Official title: Prospective Randomised Study of Doxorubicin in the Treatment of Hepatocellular Carcinoma by Drug-Eluting Bead Embolisation (PRECISION V)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Liver Cancer
Keywords: Hepatocellular Carcinoma (HCC)
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
Collaborators: name: Biocompatibles UK Ltd
First posted: 2005-12-05
Enrollment: 212
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to assess the safety and efficacy of DC Bead™ delivered by intra-arterial embolisation for the treatment of Hepatocellular Carcinoma


Eligibility criteria: Inclusion criteria

* Patients with a confirmed diagnosis of HCC according to the EASL criteria for diagnosis, see appendix 4 and staged according to the BCLC criteria.
* Patient chooses to participate and has signed the informed consent document
* Age above 18 years old
* Patients with HCC not suitable for resection or percutaneous ablation according to the BCLC Staging classification, see Figure 2.
* Patient is eligible for resection or percutaneous ablation but the treatment is unfeasible or the patient has declined. This decision must be documented in the patient's records.
* Patient is eligible for chemoembolisation prior to transplantation and the expected transplant waiting time exceeds 6 months.
* Patients who demonstrates recurrence following potentially curative treatment (resection and percutaneous ablation) who have clearly measurable disease according to RECIST or EASL
* Patients with Performance Status ECOG 0 and 1
* Patients with well preserved liver function (Child-Pugh A and B)
* Patients with bilobar disease who can be treated superselectively in a single session or both lobes able to be treated within 3 weeks.

Exclusion criteria

* Patients with another primary tumour, with the exception of conventional basal cell carcinoma or superficial bladder neoplasia
* Patients previously treated with transarterial embolisation (with or without chemotherapy).
* Patients previously treated with anthracyclines (ie doxorubicin).
* Patients' whose only measurable disease is within an area of the liver previously subjected to radiotherapy.
* Advanced liver disease:

  * Child-Pugh C,
  * active gastrointestinal bleeding,
  * encephalopathy or clinically relevant ascites.
* Bilirubin levels \>3mg/dl
* Advanced tumoural disease:

  * BCLC class C, (vascular invasion including segmental portal obstruction, extrahepatic spread or cancer-related symptoms= ECOG 2, 3 and 4) or
  * BCLC class D (WHO performance status 3 or 4, Okuda III stage) or
  * Diffuse HCC defined as \>50% tumour involvement of the whole liver
* Any contraindication for doxorubicin administration:

  * serum bilirubin \>5mg/dL,
  * WBC \<3000 cells/mm3
  * neutrophil \<1500 cells/mm3,
  * cardiac ejection fraction \<50 percent assessed by isotopic ventriculography, echocardiography or MRI
* Any contraindication for hepatic embolisation procedures:

  * porto-systemic shunt,
  * hepatofugal blood flow;
  * impaired clotting tests (platelet count \<50000/mm3, prothrombin activity \<50 percent),
  * renal insufficiency/failure, serum creatinine \> 2mg/dl (177umol/l)
  * severe atheromatosis,
  * AST and/or ALT \>5x ULN or, when greater \>250U/l
* Women who are pregnant or breast feeding
* Allergy to contrast media
* Contraindication to hepatic artery catheterisation, such as severe peripheral vascular disease precluding catheterisation
* The availability of alternative therapies those, in the judgment of the physician (referring or treating), are more appropriate for the patient
* Any co-morbid disease or condition or event that, in the investigator's judgment, would place the patient at undue risk, that would preclude the safe use of DC Bead™, or TACE
* Patients who are contraindicated for MRI

Primary outcomes:
measure: Objective response rate measured according to RECIST and EASL
timeFrame: 6 months
Secondary outcomes:
measure: Toxicity
timeFrame: 6 month
measure: Change in Alpha Fetal Protein (AFP) over time
timeFrame: 6 months
measure: Time to hospital discharge
timeFrame: 6 months
measure: Safety
timeFrame: 6 months
measure: Other procedures or interventions required
timeFrame: 6 months
measure: Cardiotoxicity
timeFrame: 6 months
measure: Local Tumour Response
timeFrame: 6 months
measure: Health care resource use
timeFrame: 6 months
measure: Patient quality of life
timeFrame: 6 months
measure: Time To Progression
timeFrame: 6 months
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medizinische Universitat Innsbruck
city: Vienna
country: Austria
facility: Allgemines Krankenhaus Vienna
city: Clichy
country: France
facility: L'Hopital Beaujon
city: Lille
country: France
facility: Hopital Claude Huriez
city: Lyon
country: France
facility: Groupement Hospitalier Edouard Herriot
city: Nice
country: France
facility: Hopital Archet II
city: Paris
country: France
facility: Hopital Pitie Salpetriere
city: Toulouse
country: France
facility: CHU Rangueil
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Frankfurt am Main
country: Germany
facility: Klinikum der Johann-Wolfgang-Goethe-Universitat
city: Hannover
country: Germany
facility: Medicinische Hochschule Hannover
city: Mainz
country: Germany
facility: Klinikum der Johannes Guttenberg
city: Mannheim
country: Germany
facility: Fakultat fur Klinische Medizin Mannheim Universitat
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Geneve
country: Switzerland
facility: Hopitaux Universitaires de Geneve
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Zurich
country: Switzerland
facility: Universitatsspital Zurich
Study officials:
affiliation: The Allgemines Krankenhaus, Vienna, 1090, Austria
name: Prof Johannes Lammer
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vogl TJ, Lammer J, Lencioni R, Malagari K, Watkinson A, Pilleul F, Denys A, Lee C. Liver, gastrointestinal, and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads: results from the PRECISION V randomized trial. AJR Am J Roentgenol. 2011 Oct;197(4):W562-70. doi: 10.2214/AJR.10.4379.