Paediatric Hepatic International Tumour Trial

The PHITT trial is an over-arching study for patients with Hepatoblastoma (HB) and Hepatocellular Carcinoma (HCC). This trial will use a risk-adapted approach to the treatment of children diagnosed with HB.

Children with HCC will be included as a separate cohort.

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

Eligibility Criteria:
Inclusion Criteria:

* Clinical diagnosis of HB\* and histologically defined diagnosis of HB or HCC.

  \*Histological confirmation of HB is required except in emergency situations where:
  * a) the patient meets all other eligibility criteria, but is too ill to undergo a biopsy safely, the patient may be enrolled without a biopsy.
  * b) there is anatomic or mechanical compromise of critical organ function by tumour (e.g., respiratory distress/failure, abdominal compartment syndrome, urinary obstruction, etc.)
  * c) Uncorrectable coagulopathy
* Age ≤30 years
* Written informed consent for trial entry

Exclusion Criteria:

* Any previous chemotherapy or currently receiving anti-cancer agents
* Recurrent disease
* Previously received a solid organ transplant; other than orthotopic liver transplantation (OLT).
* Uncontrolled infection
* Unable to follow or comply with the protocol for any reason
* Second malignancy
* Pregnant or breastfeeding women