Clinical Trial: Paediatric Hepatic International Tumour Trial

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Paediatric Hepatic International Tumour Trial

Brief Summary:

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.


Detailed Summary:

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)
  • Event-free survival (EFS) [ Time Frame: From date of randomisation (or registration into the trial for non-randomised patients), until date of first failure event, assessed up to 6 years. ]

    Event-free survival (EFS) is defined as the time from randomisation (or registration into the trial for non-randomised patients) to first failure event. Patients who have not had an event will be censored at their last follow-up date.

    Failure events are:

    • progression of existing disease or occurrence of disease at new sites,
    • death from any cause prior to disease progression,
    • diagnosis of a second malignant neoplasm.
  • Response in HCC is defined as complete (CR) or partial (PR) response according to RECIST version 1.1 criteria [ Time Frame: From date of screening assessment until date of first response assessment, up to 63 days in Group F ]
    Response in HCC is defined as complete (CR) or partial (PR) response according to RECIST version 1.1 criteria. The assessment will be performed after 3 cycles of PLADO, or 4 cycles of PLADO+S/GEMOX+S in Group F. Patients who are not assessable for response - e.g. because of early stopping of treatment or death - will be assumed to be non-responders.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Failure-free survival (FFS) [ Time Frame: From date of randomisation (or registration into the trial for non-randomised patients) until date of first failure event, or date of last follow up assessment, assessed up to 6 years. ]

    Failure-free survival (FFS) is defined as the time from randomisation (or registration into the trial for non-randomised patients) to first failure event. Patients who have not had an event will be censored at their last follow-up date.

    Failure events are:

    • progression of existing disease or occurrence of disease at new sites,
    • death from any cause prior to disease progression,
    • diagnosis of a second malignant neoplasm. failure to go to resection.
  • Overall survival (OS) [ Time Frame: From date of randomisation (or registration for non-randomised patients) until date of death from any cause, or date of last follow up assessment, assessed up to 6 years. ]
    Overall survival (OS) is defined as the time from randomisation (or registration for non-randomised patients) to death from any cause. Patients who have not died will be censored at their last follow-up date.
  • Toxicity categorized and graded using Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: From date of start of randomised treatment until date 30 days after last treatment. ]
    Toxicity will be recorded in relation to each cycle of randomised treatment and will be categorized and graded using Common Terminology Criteria for Adverse Events (CTCAE)
  • Chemotherapy-related cardiac, nephro- and oto-toxicity using Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: From date of start of randomised treatment until date 30 days after last treatment. ]
    Chemotherapy-related cardiac, nephro- and oto-toxicity will be recorded in relation to each cycle of treatment and will be categorized and graded using Common Terminology Criteria for Adverse Events (CTCAE)
  • Hearing loss according to the SIOP Boston Scale [ Time Frame: From date of registration until date of last follow up assessment, or date of death, assessed up to 6 years. ]
    Hearing loss will be measured according to the SIOP Boston Scale for oto-toxicity. The assessment will be performed at end of treatment (EOT) and follow up
  • Best Response [ Time Frame: From date of first treatment until the date of last treatment, or until the date of first documented progression or date of death, assessed up to 6 months. ]
    Best Response is defined as CR or PR and is based on radiological response (RECIST v1.1) and Alpha Fetoprotein (AFP) decline. Best Response will be measured throughout treatment period. Patients who are not assessable for response - e.g. because of early stopping of treatment or death - will be assumed to be non-responders.
  • Surgical resectability defined as complete resection, partial resection or transplant [ Time Frame: From date of registration until date of last follow up assessment, or date of death, assessed up to 6 years. ]
    Surgical resectability is defined as complete resection, partial resection or transplant
  • Adherence to surgical guidelines [ Time Frame: From date of registration until date of last follow up assessment, or date of death, assessed up to 6 years. ]
    Adherence to surgical guidelines is defined as the local clinician's surgical decision to resect or not compared to the current SIOPEL surgical guidelines.


Original Secondary Outcome: Same as current

Information By: University of Birmingham

Dates:
Date Received: December 14, 2016
Date Started: May 2017
Date Completion: December 2022
Last Updated: May 5, 2017
Last Verified: May 2017