Hepatic Cancer / Posted 1 year ago
PHITT: Paediatric Hepatic International Tumour Trial
Liver cancer in the paediatric population is rare with an incidence approximately 1 – 1.5 million population. The commonest tumour seen in the childhood population is hepatoblastoma (HB), usually seen in young children and infants. Much rarer (about 10% of paediatric liver cancers) is hepatocellular carcinoma (HCC), usually seen in the teenage population and sometimes associated with underlying cirrhotic liver diseases. The ChiLTERN project builds on a unique opportunity to undertake a comprehensive research program linked to an ambitious global partnership which will see the single largest clinical trial (the Paediatric Hepatic International Tumour Trial – PHITT) ever undertaken in this population of patients, with several randomised questions in six subgroups of patients. PHITT and ChiLTERN will allow us to move towards an era of personalised therapy in which each patient will receive the correct amount of chemotherapy and will undergo the best surgical operation (surgical resection or transplant). By using both clinical and biological information, we can assign patients more accurately to risk groups based on their survival. Using genetic tests and biomarkers, we will determine those children who may be at risk of developing long term side effects (deafness, heart failure, kidney damage). In addition, biomarkers will allow us to monitor during therapy and detect toxicities early before serious damage is done so that we can adapt treatment and prevent these problems. Finally we will be using imaging technology tools which will help our surgeons plan liver operations more safely and effectively. Ultimately PHITT and ChiLTERN will allow us to cure more children with liver cancer, expose fewer children to toxic chemotherapy and ensure their surgery is both effective and safe.
This PHITT trial will evaluate whether reducing treatment for low risk patients maintains their excellent 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 two groups, E and F based on whether the tumour is resectable (group E) or unresectable and/or metastatic (group F). The aim is to evaluate whether survival in patients in group E with de-novo HCC using PLADO chemotherapy is improved and to evaluate whether resectability and survival is improved in patients in group F using novel therapeutic agents in combination with PLADO.
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