Condition category
Cancer
Date applied
18/06/2010
Date assigned
18/06/2010
Last edited
27/06/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Mrs Sonia Fox

ORCID ID

Contact details

University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
-
TACE2@trials.bham.ac.uk

Additional identifiers

EudraCT number

2008-005073-36

ClinicalTrials.gov number

NCT01324076

Protocol/serial number

5347

Study information

Scientific title

TACE-2: a randomised placebo-controlled, double blinded, phase III trial evaluating sorafenib in combination with transarterial chemoembolisation (TACE) in patients with unresectable hepatocellular carcinoma (HCC)

Acronym

TACE-2

Study hypothesis

The aim of this study is to determine whether the addition of sorafenib to transarterial chemoembolisation (TACE) (performed according to a standardised protocol with doxorubicin eluting beads) is superior to TACE alone in the treatment of hepatocellular carcinoma (HCC).

Ethics approval

South East Research Ethics Committee, 18/03/2010, ref: 09/H1102/114

Study design

Multicentre randomised interventional treatment trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

GP practices

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Topic: National Cancer Research Network; Subtopic: Upper Gastro-Intestinal Cancer; Disease: Liver

Intervention

TACE using DC Bead loaded with doxorubicin plus sorafenib. Patient will commence oral sorafenib (400 mg twice daily) on the day of randomisation and transarterial chemoembolisation (TACE) will be performed between 2 - 5 weeks post-randomisation using DC Bead loaded with Doxorubicin-HCL (150 mg).

The control group will receive TACE plus matching placebo, as per protocol above.

The patient will continue to take sorafenib/placebo until progression according to RECIST has been externally verified. Patients will be followed up for 1 year from the last administration of sorafenib/placebo. They will be unblinded upon progression.

Follow-up length: 12 months
Study entry: single randomisation only

Intervention type

Drug

Phase

Phase III

Drug names

Sorafenib, doxorubicin

Primary outcome measures

Progression free survival (PFS)

Secondary outcome measures

Overall survival - the time between the date of randomisation and death from any cause

Overall trial start date

01/08/2010

Overall trial end date

31/08/2016

Reason abandoned

Eligibility

Participant inclusion criteria

1. Histological or cytological diagnosis or meet the American Association for the Study of Liver Diseases (AASLD) criteria for diagnosis of HCC and at least one uni-dimensional lesion measurable according to the Response Evaluation Criteria in Solid Tumours (RECIST) criteria by computed tomography (CT) scan or magnetic resonance imaging (MRI)
2. Not a candidate for surgical resection
3. Aged greater than or equal to 18 years and estimated life expectancy greater than 3 months
4. Eastern Cooperative Oncology Group (ECOG) performance status greater than or equal to 1
5. Adequate haematological function Hb greater than or equal to 9 g/L, absolute neutrophil count greater than or equal to 1.5 x 10^9/L, platelet count greater than or equal to 60 x 10^9/L
6. Bilirubin greater than or equal to 50 µmol/L, asparate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 5 x upper limit of normal (ULN), alkaline phosphatase (ALP) less than 4 x ULN
7. Adequate renal function; creatinine less than or equal to 1.5 x ULN
8. International normalised ratio (INR) greater than or equal to 1.5
9. Amylase and lipase less than 2 x ULN
10. Child-Pugh A (score less than or equal to 6)
11. Left ventricular ejection fraction greater than or equal to 45%
12. Women of child-bearing potential should have a negative pregnancy test prior to study entry. Both men and women must be using an adequate contraception method, which must be continued for 3 months after completion of treatment.
13. Written informed consent
14. Male and female, lower age limit of 18 years

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned sample size: 412; UK sample size: 300

Participant exclusion criteria

1. Extrahepatic metastasis
2. Prior embolisation, systemic or radiation therapy for HCC
3. Any contraindications for hepatic embolisation procedures procedures including portosystemic shunt, hepatofugal blood flow, known severe atheromatosis
4. Investigational therapy or major surgery within 4 weeks of trial entry
5. Any ablative therapy (radiofrequency ablation [RFA] or percutaneous ethanol injection [PEI]) for HCC (this should not exclude patients if target lesion(s) have not been treated and occurred greater than 6 weeks prior study entry)
6. History of bleeding within the past 4 weeks
7. Child-Pugh cirrhosis C or B (score greater than or equal to 7)
8. Hepatic encephalopathy
9. Ascites refractory to diuretic therapy
10. Documented occlusion of the hepatic artery or main portal vein
11. Hypersensitivity to intravenous contrast agents
12. Active clinically serious infection greater than grade 2 National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0
13. Pregnant or lactating women
14. Known history of human immunodeficiency virus (HIV) infection
15. History of second malignancy except those treated with curative intent more than three years preciously without relapse and non-melanotic skin cancer or cervical carcinoma in situ
16. Evidence of severe or uncontrolled systemic diseases, cardiac arrhythmias (requiring anti-arrhythmic therapy or pace maker), uncontrolled hypertension, congestive cardiac failure greater than New York Heart Association (NYHA) class 2, myocardial infarction (MI) within 6 months or laboratory finding that in the view of the Investigator makes it undesirable for the patient to participate in the trial
17. Psychiatric or other disorder likely to impact on informed consent
18. Patient is unable and/or unwilling to comply with treatment and study instructions
19. Patient unable to swallow oral medications

Recruitment start date

04/11/2010

Recruitment end date

07/12/2015

Locations

Countries of recruitment

France, Ireland, Italy, United Kingdom

Trial participating centre

Beatson West of Scotland Cancer Centre
Glasgow
G12 0YN

Trial participating centre

Bristol Royal Infirmary
BS2 8HW

Trial participating centre

Castle Hill Hospital
Hull
HU16 5JQ

Trial participating centre

Christie Hospital
Manchester
M20 4BX

Trial participating centre

Derriford Hospital
PL6 8DH

Trial participating centre

Freeman Hospital
Newcastle
NE7 7DN

Trial participating centre

Hammersmith Hospital
London
W12 0HS

Trial participating centre

King's College Hospital
London
SE5 9RS

Trial participating centre

Manchester Royal Infirmary
M13 9WL

Trial participating centre

Ninewells Hospital
Dundee
DD2 1UB

Trial participating centre

Norfolk and Norwich University Hospital
NR4 7UY

Trial participating centre

Queen's Medical Centre
Nottingham
NG7 2UH

Trial participating centre

Royal Devon and Exeter Hospital
EX2 5DW

Trial participating centre

Royal Gwent Hospital
NP20 2UB

Trial participating centre

Royal Infirmary of Edinburgh
EH16 4SA

Trial participating centre

Royal Liverpool University Hospital
L7 8XP

Trial participating centre

Royal Marsden Hospital
London
SW3 6JJ

Trial participating centre

Royal Marsden Hospital
Sutton
SM2 5PT

Trial participating centre

Southampton General Hospital
SO16 6YD

Trial participating centre

St Bartholomew's Hospital
EC1A 7BE

Trial participating centre

St James's University Hospital
Leeds
LS9 7TF

Trial participating centre

St Vincent's University Hospital
Dublin
D04 Y8V0

Trial participating centre

The Queen Elizabeth Hospital
Birmingham
B15 2TH

Trial participating centre

University Hospital Aintree
L9 7AL

Sponsor information

Organisation

University College London (UCL) (UK)

Sponsor details

UCL Biomedicine Research & Development Unit
Maple House
149 Tottenham Court Road
London
W1T 7NF
United Kingdom

Sponsor type

University/education

Website

http://www.ucl.ac.uk/

Funders

Funder type

Industry

Funder name

Bayer PLC (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Biocompatibles Ltd (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Cancer Research UK (CRUK) (UK) (ref: C12125/A10051)

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

1. Abstract submitted to ASCO 2016
2. Final publication in June 2017

IPD sharing plan
The datasets generated during and/or analysed during the current study are/will be available upon request, and subsequent approval by the Trial Management Group, from TACE2@trials.bham.ac.uk

Intention to publish date

30/06/2017

Participant level data

Available on request

Results - basic reporting

Publication summary

2017 results in: https://www.ncbi.nlm.nih.gov/pubmed/28648803

Publication citations

Additional files

Editorial Notes

27/06/2017: Publication reference added. 16/02/2016: The overall trial end date was changed from 30/11/2013 to 31/08/2016.