Plain English Summary
http://www.cancerhelp.org.uk/trials/a-trial-looking-combining-two-treatments-for-cancer-liver-TACE-2
Trial website
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 measure
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 (if study stopped)
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
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
Basic results (scientific)
Publication list
2017 results in: https://www.ncbi.nlm.nih.gov/pubmed/28648803