TACE TRIAL

1
TACE TRIAL A phase II/III randomised controlled
trial of trans-arterial chemoembolisation (TACE)
versus embolisation (TAE) alone in non-resectable
hepatocellular carcinoma
A North London Liver Cancer Network Trial.
Chief Investigators Dr Tim Meyer and Prof Andrew
Burroughs Coordinated at the Cancer Research UK
UCL Cancer Trial Centre, Sponsored by UCL
RATIONALE
Hepatocellular carcinoma (HCC) represents 5 of
all cancers with approximately 500,000 new cases
per year worldwide. Overall prognosis is poor
with a median survival of 4 to 6 months. Only a
minority are eligible for radical treatments such
as resection or transplantation and 80 will
therefore require alternative treatment. Systemic
chemotherapy has not been shown to improve
survival for patients with HCC. However a
meta-analysis of 7 randomised trials has
confirmed a survival advantage for TAE/TACE over
no treatment. The question of whether TACE
confers a survival benefit over TAE remains to be
answered as the studies comparing the two
treatments have been small and lack sufficient
power to show a survival benefit. Furthermore
the delivery of chemotherapy in standard TACE
protocols is likely to be sub-optimal because the
chemotherapy is given once every couple of months
and is delivered immediately prior to rendering
the tumour ischaemic. This trial will compare TAE
and TACE and will optimise the schedule so that
the procedure will be repeated 3 weekly and there
will be a 4-6 hour interval between
trans-arterial chemotherapy and embolisation.
Phase II Design
Randomisation schema
Phase III design

• Will commence on successful completion of the
  initial Phase II study .
• To detect an increase in 2-year survival from
  50 to 63 sample size will be 322 with 80 power
  and a level significance of 5
• Primary objectives
• Overall survival
• Secondary objectives
• Progression free survival
• Tumour response
• Toxicity
• QoL EORTC QLQ 30 HCC 18

• Feasibility study to determine acceptability and
  toxicity
• 80 patients (40 in each arm)
• An underlying grade 4 toxicity rate of ?30 or
  treatment-related death rate of 5 or more will
  be considered to be unacceptable.
• A local study involving a limited number or
  centres

Pre-treatment assessments
Eligibility criteria
Exclusion criteria

• Evidence of unresectable HCC
• Single hepatic tumour?3cm in diameter or
  multifocal disease
• Adequate heamatology and INR ?1.5
• Adequate renal function GFR ? 50ml/min
• Adequate liver function bilirubin ?100 mmol/l
• ECOG performance status  2
• Life expectancy greater than 3 months
• Aged ? 16
• Written informed consent

• Up to 3 wks before randomisation
• Confirmation of disease by histology or
  according to EASL criteria
• Triple phase CT scans or MRI of Liver
• CT chest abdomen and pelvis to exclude
  metastatic disease.
• Within 72 hours pre-treatment
• Clinical examinations history
• Laboratory investigations bilirubin FBC, INR,
  GFR, U Es, alpha FP etc
• ECOG Child-Pugh status
• Completion of baseline QOL forms

• Extra hepatic metastases
• Prior treatment for HCC
• Active sepsis or bleeding
• Hepatic encephalopathy
• Ascites refractory to diuretic therapy
• Documented occlusion of hepatic artery
• Hypersensitivity to iv contrast agents
• Prior malignancy likely to interfere with
  response evaluation
• Pregnant or lactating women
• Serious uncontrolled concomitant disease
• Unable to give informed consent

Post treatment assessments and follow up
Transarterial chemoembolisation
Transarterial embolisation

• Reduces/blocks the blood flow through the
  hepatic artery supplying the tumour
• Catheter inserted into the femoral artery to
  reach the hepatic artery and embolisation
  particles injected
• Patients will undergo selective angiography
  prior to embolisation
• Bilobar lesions are treated separately
• Treatment to start within 3 weeks of
  randomisation and repeated 3 times at 3 weekly
  intervals

• 2-4 wks after treatment
• CT MRI or other imaging as performed at
  baseline
• Clinical examinations history
• Laboratory investigations bilirubin FBC, INR,
  GFR, U Es, alpha FP etc
• ECOG Child-Pugh status
• QOL
• Long term follow up 3 monthly
• CT scan
• Clinical examinations and Laboratory
  investigations as before
• QOL

• Combines embolisation with direct delivery of
  chemotherapy to the tumour
• Repeat laboratory investigations including GFR
  calculation prior to every procedure
• Cisplatin 50mg in 50mls delivered directly to
  the hepatic artery through the catheter inserted
  into the femoral artery
• 4-6 hours prior to injection of embolisation
  particles
• 3 procedures at 3 weekly intervals

Contact Sara Okumu-Fransche 020 7679 8095,
s.okumu-fransche_at_ctc.ucl.ac.uk Cancer Research UK
UCL Cancer Trials Centre
October 2004