Evaluating sorafenib in combination with transarterial chemoembolisation (TACE) in patients with unresectable hepatocellular carcinoma (HCC)
| ISRCTN | ISRCTN93375053 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN93375053 |
| EudraCT/CTIS number | 2008-005073-36 |
| ClinicalTrials.gov number | NCT01324076 |
| Secondary identifying numbers | 5347 |
- Submission date
- 18/06/2010
- Registration date
- 18/06/2010
- Last edited
- 26/10/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Contact information
Mrs Sonia Fox
Scientific
Scientific
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
| TACE2@trials.bham.ac.uk |
Study information
| Study design | Multicentre randomised interventional treatment trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | GP practice |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| 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) |
| Study acronym | TACE-2 |
| Study objectives | 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(s) | South East Research Ethics Committee, 18/03/2010, ref: 09/H1102/114 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/08/2010 |
| Completion date | 31/08/2016 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned sample size: 412; UK sample size: 300 |
| Total final enrolment | 313 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 04/11/2010 |
| Date of final enrolment | 07/12/2015 |
Locations
Countries of recruitment
- France
- Ireland
- Italy
- United Kingdom
Study participating centres
Beatson West of Scotland Cancer Centre
Glasgow
G12 0YN
United Kingdom
G12 0YN
United Kingdom
Bristol Royal Infirmary
BS2 8HW
United Kingdom
United Kingdom
Castle Hill Hospital
Hull
HU16 5JQ
United Kingdom
HU16 5JQ
United Kingdom
Christie Hospital
Manchester
M20 4BX
United Kingdom
M20 4BX
United Kingdom
Derriford Hospital
PL6 8DH
United Kingdom
United Kingdom
Freeman Hospital
Newcastle
NE7 7DN
United Kingdom
NE7 7DN
United Kingdom
Hammersmith Hospital
London
W12 0HS
United Kingdom
W12 0HS
United Kingdom
King's College Hospital
London
SE5 9RS
United Kingdom
SE5 9RS
United Kingdom
Manchester Royal Infirmary
M13 9WL
United Kingdom
United Kingdom
Ninewells Hospital
Dundee
DD2 1UB
United Kingdom
DD2 1UB
United Kingdom
Norfolk and Norwich University Hospital
NR4 7UY
United Kingdom
United Kingdom
Queen's Medical Centre
Nottingham
NG7 2UH
United Kingdom
NG7 2UH
United Kingdom
Royal Devon and Exeter Hospital
EX2 5DW
United Kingdom
United Kingdom
Royal Gwent Hospital
NP20 2UB
United Kingdom
United Kingdom
Royal Infirmary of Edinburgh
EH16 4SA
United Kingdom
United Kingdom
Royal Liverpool University Hospital
L7 8XP
United Kingdom
United Kingdom
Royal Marsden Hospital
London
SW3 6JJ
United Kingdom
SW3 6JJ
United Kingdom
Royal Marsden Hospital
Sutton
SM2 5PT
United Kingdom
SM2 5PT
United Kingdom
Southampton General Hospital
SO16 6YD
United Kingdom
United Kingdom
St Bartholomew's Hospital
EC1A 7BE
United Kingdom
United Kingdom
St James's University Hospital
Leeds
LS9 7TF
United Kingdom
LS9 7TF
United Kingdom
St Vincent's University Hospital
Dublin
D04 Y8V0
Ireland
D04 Y8V0
Ireland
The Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom
B15 2TH
United Kingdom
University Hospital Aintree
L9 7AL
United Kingdom
United Kingdom
Sponsor information
University College London (UCL) (UK)
University/education
University/education
UCL Biomedicine Research & Development Unit
Maple House
149 Tottenham Court Road
London
W1T 7NF
England
United Kingdom
| Website | http://www.ucl.ac.uk/ |
|---|---|
"ROR" |
https://ror.org/02jx3x895 |
Funders
Funder type
Industry
Bayer PLC (UK)
No information available
Biocompatibles Ltd (UK)
No information available
Cancer Research UK (CRUK) (UK) (ref: C12125/A10051)
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/06/2017 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| 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 |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/08/2017 | Yes | No | |
| Plain English results | 26/10/2022 | No | Yes | ||
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
25/10/2022: Cancer Research UK plain English results link and total final enrolment added.
27/06/2017: Publication reference added.
16/02/2016: The overall trial end date was changed from 30/11/2013 to 31/08/2016.
