Paediatric Hepatic International Tumour Trial

The trial will evaluate whether reducing treatment for low risk HB patients maintains

their excellent event free survival (EFS) and decreases acute and long-term toxicity.

Intensification of therapy with the use of novel agents will be evaluated in the high

risk group. The trial will also compare three different regimens in intermediate risk HB.

Patients with HCC will be divided into groups based on whether the tumour is resectable

or unresectable and/or metastatic.

Evaluation of the biology of HB and HCC, using the identification/validation of novel and

already reported prognostic biomarkers as well as toxicity biomarkers is a key strand of

this trial, so patients in all risk groups can be registered. The trial is also designed

to optimise the collection of clinically annotated biologic specimens and establish the

world's largest repository of blood and tissue samples from paediatric patients with HB

and HCC.

The trial includes 4 randomised comparisons addressing therapeutic questions. For low

risk HB patients, outcome with a total of 4 cycles of treatment is not inferior to those

receiving a total of 6 cycles of treatment.

For intermediate risk patients, 3 regimens will be compared for outcome and toxicity.

For high risk patients, 2 post induction regimens will be compared for outcome. For

resected HCC patients, the addition of GEMOX to PLADO regimen will be compared.

In addition the following will be assessed:

- To validate a new global risk stratification, defined by Children's Hepatic Tumours

International Collaboration (CHIC)

- To evaluate clinically relevant factors, including the following:

- Provide a comprehensive and highly-validated panel of diagnostic and prognostic

biomarkers

- Determine if paediatric HCC is a biologically different entity to adult HCC

- Develop genomic and/or biomarker analysis to predict children who may have an

increased risk of developing toxicity with chemotherapy.

- To establish a collection of clinically and pathologically-annotated biological

samples.

- Evaluate a surgical planning tool for an impact on decision making processes in

POST-TEXT III and IV HB